heroin and Heroin-Dependence

Topics: Brain; Craving; Cues; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Neuroanatomy; Opioid-Related Disorders

As societal attitudes toward narcotics have changed, harm reduction strategies have emerged which make it safer to inject intravenous drugs. Diamorphine (heroin) is commonly sold as its free base-better known as brown-which has extremely poor aqueous solubility. As such, it needs to be chemically modified (cooked) to enable administration. Needle exchange programmes commonly supply citric or ascorbic acids which facilitate intravenous administration by increasing heroin solubility. If heroin users mistakenly add too much acid, the low solution pH can cause damage to their veins and, after repeated injury, could result in the loss of that injection site. Currently, advice cards supplied with these exchange kits suggest that the acid should be measured in pinches, which could result in considerable error. This work employs Henderson-Hasselbalch models to analyse the risk of venous damage by placing solution pH within the context of the buffer capacity of the blood. These models also highlight the significant risk of heroin supersaturation and precipitation within the vein, an event that has the potential to cause further harm to the user. This perspective closes with a modified administration method which could be included as part of a wider harm reduction package.

Topics: Harm Reduction; Heroin; Heroin Dependence; Humans; Narcotics; Substance Abuse, Intravenous

Heroin is an opioid agonist commonly abused for its rewarding effects. Since its synthesis at the end of the nineteenth century, its popularity as a recreational drug has ebbed and flowed. In the last three decades, heroin use has increased again, and yet the pharmacology of heroin is still poorly understood. After entering the body, heroin is rapidly deacetylated to 6-monoacetylmorphine (6-MAM), which is then deacetylated to morphine. Thus, drug addiction literature has long settled on the notion that heroin is little more than a pro-drug. In contrast to these former views, we will argue for a more complex interplay among heroin and its active metabolites: 6-MAM, morphine, and morphine-6-glucuronide (M6G). In particular, we propose that the complex temporal pattern of heroin effects results from the sequential, only partially overlapping, actions not only of 6-MAM, morphine, and M6G, but also of heroin per se, which, therefore, should not be seen as a mere brain-delivery system for its active metabolites. We will first review the literature concerning the pharmacokinetics and pharmacodynamics of heroin and its metabolites, then examine their neural and behavioral effects, and finally discuss the possible implications of these data for a better understanding of opioid reward and heroin addiction. By so doing we hope to highlight research topics to be investigated by future clinical and pre-clinical studies.

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Morphine; Morphine Derivatives

Randomised controlled trials in Europe and Canada have shown that supervised heroin assisted treatment (HAT) is an effective treatment option for people with long-term heroin addictions for whom the standard opioid substitution treatments (OST) have not been effective. This review aims to evaluate the effectiveness of supervised HAT and analyse the significance of context and implementation in the design of successful HAT programmes.. PubMed, CENTRAL, Embase, and Web of Science were searched to identify randomised controlled trials (RCT) and systematic reviews evaluating supervised HAT compared to any other OST. Studies were eligible for inclusion if they were published in English, evaluated a supervised form of HAT, and included illegal drug use and/or health as a primary outcome measure. There were no restrictions on publication date. The following outcomes of the included studies were analysed using narrative synthesis and meta-analysis where possible: retention, street drug use, health, and social functioning.. Nine randomised controlled trials spanning eight studies (n = 2331) and three systematic reviews met the inclusion criteria. Seven of the eight studies compared HAT to methadone maintenance treatment (MMT). One study compared HAT to injectable hydromorphone in a double-blind non-inferiority trial. Meta-analysis was performed on pooled results of retention across all included studies and found that HAT has a statistically significant effect on retention [Z = 7.65 (P > 0.0001)]. Five of the eight included studies found that supervised HAT reduces participants' use of illegal drugs more significantly than MMT. Evidence of improved health in participants receiving supervised HAT compared to other OSTs was inconsistent; positive effects were observed in three of the included studies (n = 1626).. When compared to methadone maintenance treatment (MMT), heroin assisted treatment (HAT) more consistently retains people with heroin addictions in treatment and reduces their consumption of illicit drugs.. PROSPERO registration: CRD42022341306.

Topics: Heroin; Heroin Dependence; Humans; Illicit Drugs; Methadone; Narcotics; Opiate Substitution Treatment; Randomized Controlled Trials as Topic; Treatment Outcome

Several randomized controlled trials (RCTs) conclude that heroin-assisted-treatment (HAT) has a larger benefit-cost ratio than oral methadone because HAT more reliably and substantially reduces participants' criminal activity. This review: (1) summarizes results from RCTs concerning the comparative effectiveness of HAT for reducing criminal activity and (2) examines the role of different mechanisms for explaining changes in crime.. Systematic search of five databases for RCTs evaluating comparative effectiveness of HAT on participant crime outcomes and potential mediators of crime. Narrative synthesis with tabular comparisons of outcomes extracted across RCTs.. Europe and Canada.. Twenty studies, spanning 10 RCTs with 2427 participants, met inclusion criteria.. HAT compared to other treatments for opioid use disorder, primarily oral methadone.. The primary outcome was criminal activity. Mediator outcomes included illicit heroin use, drug expenditures, employment and earnings and social functioning.. All trials found significantly reduced criminal activity among HAT participants, and four found significantly larger reductions for HAT compared to control condition [median odds ratios (ORs) = 0.45]. Reductions in crime are concentrated in drug-related and property offenses (ORs range from 0.14 to 0.90 and from 0.12 to 1.89, respectively). Comparative efficacy of HAT for reducing illicit heroin use probably explains reductions in drug possession offenses, but does not show consistent correlation with drug dealing or property offenses. While three trials showed reductions in drug expenditures as possibly driving crime reductions, others did not report expenditures. There is little evidence that treatment effects on economic and social functioning outcomes explain within-trial changes in criminal activity.. Existing literature suggests that heroin-assisted treatment reduces criminal activity, but trials varied in whether these effects exceeded those from oral methadone treatment. Inconsistency in outcome measures across trials complicates understanding drivers of heterogeneity. More detailed information on legal and illegal income, drug expenditures and social interactions could improve our understanding of the causal mechanisms underlying the effect of heroin-assisted-treatment on crime.

Topics: Crime; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Randomized Controlled Trials as Topic

To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence.. The PubMed, Embase, Web of Science and PsycINFO databases were searched. Eleven published studies were identified and selected based on defined eligibility and exclusion criteria.. Four pharmacokinetic studies reported negligible plasma concentrations of diacetylmorphine and its active metabolite 6-monacetylmorphine. Among six pharmacodynamic studies, three trials showed that oral diacetylmorphine reduced opioid withdrawal symptoms, one open-label pilot study reported that two patients experienced a modest 'rush' after oral diacetylmorphine and two studies found that patients could not distinguish between oral diacetylmorphine, methadone, or morphine. Regarding the clinical studies, a Swiss prospective cohort study in patients with heroin dependence showed high retention rates of oral diacetylmorphine treatment with few serious adverse events, whereas in the Canadian SALOME trial, oral diacetylmorphine treatment was prematurely discontinued because treatment retention of oral diacetylmorphine was lower than injectable diacetylmorphine maintenance treatment. Finally, two case studies illustrate the limitations and potential problems of oral diacetylmorphine in the treatment of treatment-refractory heroin dependent patients.. Based on all published data, it is unlikely that oral diacetylmorphine produces a substantial 'rush'. Prescription of oral diacetylmorphine might therefore be effective only for treatment-refractory patients with heroin dependence (i) as maintenance treatment for those who never injected or inhaled opioids; (ii) as maintenance treatment for those who want to switch from injection to oral administration of diacetylmorphine; and/or (iii) to reduce opioid withdrawal symptoms.

Topics: Administration, Oral; Canada; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Pilot Projects; Prospective Studies

This project offers new epidemiological estimates for DSM-IV cocaine dependence among sub-groups of newly incident cocaine users in the United States (US), including estimated attack rates for 21 dependence-related cocaine side effect problems and experiences occurring <12 months after onset.. In 2002-2016, US National Surveys on Drug Use and Health (NSDUH) sampled, recruited, and assessed cocaine experiences of non-institutionalized civilians. Unweighted estimates for year-pairs (2002-3,…,2015-16) are from 3488 cocaine powder-only initiates and 275 powder-then-crack initiates (all evaluated <12 months after onset). Analysis-weighted attack rate estimates are incidence proportions with 95% confidence intervals (CI), summarized via meta-analysis.. Evaluated <12 months after onset, meta-analysis summaries show 5% of powder-only initiates developed cocaine dependence (95% CI = 4%, 6%) versus 22% of powder-then-crack initiates (95% CI = 17%, 29%). For several cocaine side effect problems and experiences (e.g., 'loss of control' indicators) there is a statistically robust crack-associated excess risk.. Three interpretations of observed crack-associated excess risk are especially cogent and deserving of continued inquiry: (1) Powder-then-crack initiates start with heightened dependence risk susceptibilities (i.e., pre-dating onset); (2) Powder-using initiates become cocaine dependent and then start using crack; (3) The cocaine delivery variant of 'crack-smoking' is more toxic than powder insufflation. For powder-then-crack initiates, the cocaine dependence risk (22%) is modestly lower but statistically undifferentiable from a recently estimated risk of heroin dependence <12 months after heroin onset (30%). Clinicians can use these side effect estimates in an evidence-based diagnostic workup when patients disclose new onsets of cocaine use.

Topics: Adult; Cocaine; Cocaine-Related Disorders; Female; Health Surveys; Heroin; Heroin Dependence; Humans; Incidence; Male; Middle Aged; Powders; Syndrome; Time Factors; United States

Chronic drug exposure is hypothesized to recruit negative reinforcement processes that increase the magnitude and alter the mechanisms of drug reinforcement. Candidate substrates of negative reinforcement include increased signaling via stress-related neurotransmitters such as corticotropin releasing factor (CRF, acting at CRF receptors) or dynorphin (acting at kappa opioid receptors) and/or decreased signaling via reward-related neurotransmitters such as dopamine. Determinants of drug reinforcement can be examined with choice procedures, in which subjects choose between a drug of interest (e.g. heroin or cocaine) and a non-drug alternative reinforcer (e.g. food). This review summarizes evidence collected from studies of drug choice in rhesus monkeys to address the negative reinforcement hypothesis. In monkeys choosing between heroin and food, chronic heroin exposure and subsequent withdrawal produces a robust increase in heroin choice. This withdrawal-associated increase in heroin choice is blocked by morphine and by other mu opioid agonists used to treat opioid use disorder (methadone, buprenorphine); however, withdrawal-associated increases in heroin choice are not reliably blocked by antagonists of CRF or kappa opioid receptors or by an indirect dopamine agonist. In monkeys choosing between cocaine and food, chronic cocaine exposure and withdrawal fail to increase cocaine choice or alter sensitivity of cocaine choice to treatment with candidate therapeutics including an indirect dopamine agonist and a kappa opioid receptor antagonist. These results support a role for negative reinforcement in self-administration of heroin but not cocaine. The constellation of neurobiological changes that constitutes the negative reinforcing stimulus in opioid-dependent rhesus monkeys remains to be determined.

Topics: Animals; Choice Behavior; Cocaine; Cocaine-Related Disorders; Disease Models, Animal; Food; Heroin; Heroin Dependence; Humans; Macaca mulatta; Narcotic Antagonists; Opioid-Related Disorders; Reinforcement, Psychology; Substance Withdrawal Syndrome

Clandestine heroin laboratories have been a feature of the Malaysian illicit drug scene since soon after the abuse of heroin emerged in 1972. The first few clandestine heroin laboratories which synthesised heroin via the acetylation of imported morphine were uncovered in 1973 and 1977. By the mid-1980s, this type of laboratory was replaced by heroin-cutting laboratories whereby imported high-grade heroin was cut to street heroin. This was to meet the rising demand for the drug owing to the rapid escalation of the number of drug users. Over the years, the most significant change in the composition of the street heroin is the decrease in its purity from 30%-50% to 3%-5%. Caffeine has remained the major adulterant and chloroquine is detected in virtually all recent seizures.

Topics: Drug Contamination; Heroin; Heroin Dependence; Humans; Illicit Drugs; Malaysia; Singapore

Confirmation or exclusion of recent heroin consumption is still one of the major challenges for forensic and clinical toxicologists. A great variety of biomarkers is available for heroin abuse confirmation, including various opium alkaloids (eg, morphine, codeine), street heroin impurities (eg, 6-acetylcodeine [6-AC], noscapine, papaverine) as well as associated metabolites (eg, 6-monoacetylmorphine [6-MAM], morphine glucuronides). However, the presence of most of these biomarkers cannot solely be attributed to a previous heroin administration but can, among other things, also be due to consumption of poppy seed products ('poppy seed defense'), opium preparations or specific medications, respectively. A reliable allocation is of great importance in different contexts, for instance in the case of DUID (driving under the influence of drugs) investigations, in driving licence re-granting processes, in workplace drug testing (WDT), as well as in post-mortem identification of illicit opiate use. Additionally, differentiation between illicit street heroin abuse and pharmaceutical heroin administration is also important, especially within the frame of heroin-assisted treatments. Therefore, analysis of multiple biomarkers is recommended when illicit opiate consumption is assumed to obtain the most reliable results possible. Beyond that, interpretation of positive opiate test results requires a profound insight into the great variety of biomarkers available and their validity regarding the alleged consumption. This paper aims to provide an overview of the wide variety of heroin abuse biomarkers described in the literature and to review them regarding their utility and reliability in daily routine analysis.

Topics: Biomarkers; Codeine; Glucuronides; Heroin; Heroin Dependence; Humans; Morphine Derivatives; Opium; Reproducibility of Results; Substance Abuse Detection

Opioid addiction affects approximately 2.4 million Americans. Nearly 1 million individuals, including a growing subset of 21 000 minors, abuse heroin. Its annual cost within the United States amounts to $51 billion. Inhaled heroin use represents a global phenomenon and is approaching epidemic levels east of the Mississippi River as well as among urban youth. Chasing the dragon (CTD) by heating heroin and inhaling its fumes is particularly concerning, because this method of heroin usage has greater availability, greater ease of administration, and impressive intensity of subjective experience (high) compared with sniffing or snorting, although it also has a safer infectious profile compared with heroin injection. This is relevant owing to peculiar and often catastrophic brain complications. Following the American Medical Association Opioid Task Force mandate, we contribute a description of the pharmacology, pathophysiology, clinical spectrum, neuroimaging, and neuropathology of CTD leukoencephalopathy, as distinct from other heroin abuse modalities.. The unique spectrum of CTD-associated health outcomes includes an aggressive toxic leukoencephalopathy with pathognomonic neuropathologic features, along with sporadic instances of movement disorders and hydrocephalus. Clinical CTD severity is predominantly moderate at admission, frequently unmodified at discharge, and largely improved in the long term. Mild cases survive with minor sequelae, while moderate to severe presentations might deteriorate and progress to death. Other methods of heroin use may complicate with stroke, seizure, obstructive hydrocephalus, and (uncharacteristically) leukoencephalopathy.. The distinct pharmacology of CTD correlates with its specific clinical and radiological features and prompts grave concern for potential morbidity and long-term disability costs. Proposed diagnostic criteria and standardized reporting would ameliorate the limitations of CTD literature and facilitate patient selection for a coenzyme Q10 therapeutic trial.

Topics: Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Narcotics

Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable, to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover, behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games.

Topics: Animals; Brain; Heroin; Heroin Dependence; Humans; Narcotics; Rest

Six recent randomised control trials (RCTs) have suggested that supervised injectable heroin (SIH) can be effective in patients who persist in street heroin use during methadone treatment. However, short-term randomised control trials have limitations in assessing the effectiveness of treatments for addictive disorders, which are chronic and relapsing disorders of motivation. These RCTs particularly fail to capture the process of the SIH treatment and the diversity of influence and change over time.. This narrative review is based on the analysis of published data. Conclusions are drawn from a process of reflection informed by experience in delivering one of the published trials, subsequent experiences in varying the way SIH is delivered, and through consideration of possible mechanisms of action of SIH.. Many long-term, socially marginalised and demoralised people who are addicted to heroin experience few rewards from the stability afforded by methadone treatment. Supervised injected heroin is sufficiently reinforcing for many of these individuals to attend daily and participate in highly structured treatment. With an adequate daily dose of supervised methadone to avoid withdrawal dysphoria, occasional diamorphine injections-not necessarily twice daily, or even every day-is enough to hold people in treatment. Participation was associated with reduced amounts of non-prescribed drug use, a gradual change in self-image and attitude, and for some subjects, a movement towards social reintegration and eventual withdrawal from SIH.. Prescribed heroin is sufficiently motivating to hold a proportion of recidivist addicts in long-term treatment. Participation in structured treatment provides respite from compulsive drug use, and a proportion of subjects develop sufficient rewards from social reintegration to successfully withdraw from treatment. Such change, when it occurs, is slow and stuttering.

Topics: Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Opiate Substitution Treatment

Topics: Adult; Device Removal; Drug Eruptions; Drug Implants; Heroin; Heroin Dependence; Humans; Male; Naltrexone; Prostheses and Implants

A review of the evidence was conducted regarding asthma associated with the use of cocaine, heroin, and marijuana.. A search of the English literature was performed via PubMed/Medline and EMBASE using the search terms asthma AND cocaine, heroin, and marijuana. When pertinent articles were found, salient references in those articles were assessed.. Due to the relatively small number of studies, we included all studies and cases.. For several decades, case reports, retrospective studies, and laboratory investigations have demonstrated that inhalation of cocaine or heroin is associated with increased asthma symptoms and reduced pulmonary function. Smoking crack cocaine, nasal insufflation of cocaine or heroin, and smoking heroin increases the risk of emergency department visits and hospitalizations for asthma. Although frequent smoking of marijuana may cause symptoms of cough, sputum production, and wheezing in the general population, more studies are needed specifically in patients with asthma. Smoking marijuana with concomitant tobacco use is common and further worsens the respiratory symptoms.. Use of cocaine and heroin in patients with asthma should be avoided. Pending further studies, it would be prudent for patients with asthma to avoid smoking marijuana. Clinicians need to be vigilant regarding use of these drugs in their patients with hyperreactive airway disease.

Topics: Administration, Inhalation; Asthma; Cannabis; Cocaine-Related Disorders; Crack Cocaine; Heroin; Heroin Dependence; Humans; Marijuana Abuse; Marijuana Smoking; Respiratory Function Tests; Respiratory Sounds; Retrospective Studies; Substance-Related Disorders

Topics: Adolescent; Adult; Age Distribution; Analgesics, Opioid; Child; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Opioid-Related Disorders; Oxycodone; Prescription Drug Misuse; United States; Young Adult

After a long lead time the substitution with diamorphine was taken into the German catalogue of statutory health insurance in 2010. Currently about 570 patients are treated this way in 9 ambulances in Germany. The study phase as well as the clinical practice are showing the success of this therapy concerning physical and mental health of patients and their circumstances of social life. Thereby substitution with diamorphine is underlying very strict admission criteria regarding patients on the one hand and particular organizational requirements of the medical institution on the other hand. This article explains these criteria in detail as well as neurobiological information and clinical workflow is presented. Improvement of mandatory requirements could lead to a better reaching of patients who benefit from substitution with diamorphine.

Topics: Germany; Heroin; Heroin Dependence; Humans; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders

Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring of online drug fora, online drug marketplaces, and unregulated pharmacies.

Topics: Amphetamine-Related Disorders; Amphetamines; Central Nervous System Stimulants; Heroin; Heroin Dependence; Humans; Illicit Drugs; Internet

This narrative review aims to provide a brief history of the development of the heroin overdose field by discussing a selection of major 'classics' from the latter part of the 20th century.. Papers considered landmarks were selected from 1972, 1977, 1983, 1984 and 1999.. Findings of earlier works suggest much of what later research was to demonstrate. These include arguing that overdoses occurred primarily among tolerant older users, that most 'overdose' deaths involved low morphine concentrations, that most overdoses involve polypharmacy, that drug purity has only a moderate influence on overdose rates and that instant death following heroin administration is rare.. Landmark studies of heroin overdose from the 1970s, 1980s and 1990s laid the foundations for subsequent overdose research, mainly by identifying the major demographic characteristics of overdose cases, risk factors, survival times and behaviours at overdose events.

Topics: Drug Overdose; Heroin; Heroin Dependence; History, 20th Century; Risk Factors; Time Factors

Drug use can be defined as a kind of self destruction, and it is directly linked to attitudes toward death and suicide occurring in a significant number of users of different narcotics. The aim of the authors was to look for the background of this relationship between drug and death and examine the origin, development, and motives behind heroin overdose based on an analysis of previous studies. It seems clear that pure heroin overdose increased gradually over the years. The fear of the police is the inhibitory factor of the overdose prevention and notification of emergency health care service. Signs of suicide could be the own home as the chosen location for heroin overdose and the presence of partners ("moment of death companion"). Interventions should include simple techniques such as first aid, naloxone administration, resuscitation, prevention of relapse of prisoners and social network extension involving maintenance programs.. A droghasználatot önmagában is öndestrukciónak tekinthetjük, így közvetve kötődik a halállal kapcsolatos attitűdhöz, és jelentős számban fordul elő különböző, a narkotikumok által okozott suicidium a droghasználók körében. A tanulmány célja, hogy feltárja a drog–halál kapcsolat eredetét, hátterét, és azon belül a heroin okozta túladagolások okait a témával foglalkozó tanulmányok elemzésével, eredményeik összefoglalásával. A tiszta heroinos túladagolók életkora az évek folyamán fokozatosan nő. A rendőrségtől való félelem a túladagolás megelőzését és a mentők értesítését gátló tényező. Az öngyilkosság szándékosságára utaló jel lehet a saját otthon mint választott hely, vagy a társak jelenléte, ami a halál pillanatában biztosított társat jelentheti. (Azt, hogy nincsenek egyedül a túladagolás pillanatában.) Ezért a segítségnyújtás egyszerűbb technikáit kell bevezetni: elsősegélynyújtás, naloxonbeadás, újraélesztés, a börtönviseltek visszaesésének megelőzése, a szociális háló kiterjesztése, a fenntartó programokba való bevonás. Orv. Hetil., 2015, 156(9), 352–357.

Topics: Drug Overdose; Emergency Medical Services; Emergency Treatment; Europe; Fear; Friends; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists; Narcotics; Police; Prisoners; Resuscitation; Suicide, Attempted; United States

Supervised injectable heroin (SIH) treatment has emerged over the past 15 years as an intensive treatment for entrenched heroin users who have not responded to standard treatments such as oral methadone maintenance treatment (MMT) or residential rehabilitation.. To synthesise published findings for treatment with SIH for refractory heroin-dependence through systematic review and meta-analysis, and to examine the political and scientific response to these findings.. Randomised controlled trials (RCTs) of SIH treatment were identified through database searching, and random effects pooled efficacy was estimated for SIH treatment. Methodological quality was assessed according to criteria set out by the Cochrane Collaboration.. Six RCTs met the inclusion criteria for analysis. Across the trials, SIH treatment improved treatment outcome, i.e. greater reduction in the use of illicit 'street' heroin in patients receiving SIH treatment compared with control groups (most often receiving MMT).. SIH is found to be an effective way of treating heroin dependence refractory to standard treatment. SIH may be less safe than MMT and therefore requires more clinical attention to manage greater safety issues. This intensive intervention is for a patient population previously considered unresponsive to treatment. Inclusion of this low-volume, high-intensity treatment can now improve the impact of comprehensive healthcare provision.

Topics: Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Randomized Controlled Trials as Topic; Treatment Outcome

Multiple organ dysfunction syndrome (MODS) has rarely been described in patients with heroin intoxication. Here, we report a rare case of MODS involving six organs, due to heroin intoxication. The patient was a 32-year-old Chinese man with severe heroin intoxication complicated by acute pulmonary edema and respiratory insufficiency, shock, myocardial damage and cardiac insufficiency, rhabdomyolysis and acute renal insufficiency, acute liver injury and hepatic insufficiency, toxic leukoencephalopathy, and hypoglycemia. He managed to survive and was discharged after 10 weeks of intensive care. The possible pathogenesis and therapeutic measures of MODS induced by heroin intoxication and some suggestions for preventing and treating severe complications of heroin intoxication, based on clinical evidence and the pertinent literature, are discussed in this report.

Topics: Adult; Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Male; Multiple Organ Failure; Tomography, X-Ray Computed; Treatment Outcome

Heroin addiction is one of the most devastating and expensive of public health problems. The most effective treatment is opioid replacement therapy. Replacement of heroin, a short-acting euphoriant with methadone or other opioids that have significantly longer duration of action provides a number of therapeutic benefits. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Opioid-based detoxification is based on the principle of cross-tolerance, in which one opioid is replaced with another one that is slowly tapered. For the treatment of heroin addicts a wide range of psychosocial and pharmacotherapeutic treatments are available; of these, methadone maintenance therapy has the most evidence of benefit. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rate and criminality associated with heroin use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. Buprenorphine which is a long-acting partial agonist was also approved as pharmacotherapy for opioid dependence. Opioid antagonists can reduce heroin self-administration and opioid craving in detoxified addicts. Naltrexone, which is a long-acting competitive antagonist at the opioid receptors, blocks the subjective and objective responses produced by intravenous opioids. Naltrexone is employed to accelerate opioid detoxification by displacing heroin and as a maintenance agent for detoxified formerly heroin-dependent patients who want to remain opioid-free.

Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics, Opioid; Buprenorphine; Euphoria; Heroin; Heroin Dependence; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment

The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence.

Topics: Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Time Factors; Treatment Outcome

For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some 'nonresponders' and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy.

Topics: Buprenorphine; Drug Overdose; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Reinforcement, Psychology; Substance Withdrawal Syndrome; Time Factors

A majority of studies have shown a link between the common functional rs6265 polymorphism of the BDNF gene and susceptibility to drug dependence. However, the pattern of results is inconsistent. To precisely evaluate this association, a systematic review and meta-analysis of previous case-control reports was conducted. Data from 20 studies containing 9419 participants (4665 cases and 4754 controls) conducted between 2004 and 2013 restricted to alcohol, nicotine, heroin, substance and methamphetamine dependency were meta-analyzed. Following quality control of the results, a significant association between C allele and methamphetamine dependence remained in south Asian subjects (p = 0.004). Similar results were detected in south Asian subjects for methamphetamine dependence and in Chinese subjects for heroin dependence under an autosomal codominant genotype model (TT vs CC, p = 0.005 and p = 0.0004, respectively). In conclusion, the rs6265 polymorphism may be a risk factor for methamphetamine dependence in south Asian subjects or for heroin dependence in Chinese subjects.

Topics: Alcohols; Asian People; Brain-Derived Neurotrophic Factor; Genetic Predisposition to Disease; Genotype; Heroin; Heroin Dependence; Humans; Methamphetamine; Polymorphism, Genetic; Substance-Related Disorders

All prenatal care providers should offer routine voluntary substance use screening to all patients. Parturients who screen positive for illicit substances require a multidisciplinary team approach to drug rehabilitation and prenatal care. This review will examine the pharmacological properties and the neonatal consequences of the use of opioids and amphetamines. Substance-abusing parturients typically abuse multiple substances simultaneously and have other comorbidities including psychosocial instability and mental illness. These comorbidities must be effectively addressed to achieve optimal health outcomes for both mother and infant.

Topics: Amphetamine-Related Disorders; Amphetamines; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Narcotics; Opioid-Related Disorders; Postnatal Care; Pregnancy; Pregnancy Complications; Prenatal Care; Prescription Drugs; Substance Abuse Detection

Maintaining opiate addicts on opiates has a long history. The idea to prescribe pharmaceutical morphine as a substitute for street heroin started in USA and was abolished on the basis of prohibitionist legislation. A new approach to maintain opiate addicts on substitution therapy was initiated in USA in 1963, with the prescription of methadone. This approach found, although slowly, increasing acceptance, and is nowadays considered to be a cornerstone in the management of opiate dependence and for the prevention of HIV/AIDS in opiate injectors. Since 1975, the concept of heroin maintenance treatment was re-activated in order to reach out to treatment-resistant heroin addicts. Research projects were performed in Switzerland, the Netherlands, Germany, Spain, Canada and in England, another one is planned in Belgium. Based on the unanimously positive outcomes, heroin maintenance has become routine treatment for otherwise untreatable heroin addicts in Switzerland, the Netherlands, Germany and England, and Denmark has set up heroin maintenance without new research trials.

Topics: Canada; Clinical Trials as Topic; Europe; Health Policy; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Research Design; Treatment Outcome; World Health Organization

Several types of medications have been used for stabilizing heroin users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The present review focuses on the prescription of heroin to heroin-dependent individuals.. To compare heroin maintenance to methadone or other substitution treatments for opioid dependence regarding: efficacy and acceptability, retaining patients in treatment, reducing the use of illicit substances, and improving health and social functioning.. A review of the Cochrane Central Register of Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to november 2009), EMBASE (1980 to 2005) and CINAHL until 2005 (on OVID) was conducted. Personal communications with researchers in the field of heroin prescription identified ongoing trials.. Randomised controlled trials of heroin maintenance treatment (alone or combined with methadone) compared with any other pharmacological treatment for heroin-dependent individuals.. Two reviewers independently assessed trial quality and extracted data.. Eight studies involving 2007 patients met the inclusion criteria. Five studies compared supervised injected heroin plus flexible dosages of methadone treatment to oral methadone only and showed that heroin helps patients to remain in treatment (valid data from 4 studies, N=1388 Risk Ratio 1.44 (95%CI 1.19-1.75) heterogeneity P=0.03), and to reduce use of illicit drugs. Maintenance with supervised injected heroin has a not statistically significant protective effect on mortality (4 studies, N=1477 Risk Ratio 0.65 (95% CI 0.25-1.69) heterogeneity P=0.89), but it exposes at a greater risk of adverse events related to study medication (3 studies N=373 Risk Ratio 13.50 (95% CI 2.55-71.53) heterogeneity P=0.52). Results on criminal activity and incarceration were not possible to be pooled but where the outcome were measured results of single studies do provide evidence that heroin provision can reduce criminal activity and incarceration/imprisonment. Social functioning improved in all the intervention groups with heroin groups having slightly better results. If all the studies comparing heroin provision in any conditions vs any other treatment are pooled the direction of effect remain in favour of heroin.. The available evidence suggests an added value of heroin prescribed alongside flexible doses of methadone for long-term, treatment refractory, opioid users, to reach a decrease in the use of illicit substances, involvement in criminal activity and incarceration, a possible reduction in mortaliity; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment for people who are currently or have in the past failed maintenance treatment, and it should be provided in clinical settings where proper follow-up is ensured.

Topics: Adult; Crime; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Patient Compliance; Randomized Controlled Trials as Topic; Young Adult

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin's effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment.

Topics: Animals; Drug Delivery Systems; Drug Discovery; Heroin; Heroin Dependence; Humans; Immunoconjugates; Psychotropic Drugs; Vaccines

Heroin is an illicit, highly addictive drug. It is either the most abused or the most rapidly acting member of opioids. Abusers describe a feeling of a surge of pleasurable sensation, named as "rush" or "high". Repeated administration of high doses of heroin results in the induction of physical dependence. Physical dependence refers to an altered physiological state produced by chronic administration of heroin which necessitates the continued administration of the drug to prevent the appearance of a characteristic syndrome, the opioid withdrawal or abstinence syndrome. Withdrawal symptoms may occur within a few hours after the last administration of heroin. Symptoms of the withdrawal include restlessness, insomnia, drug craving, diarrhea, muscle and bone pain, cold flashes with goose bumps, and leg movements. Major withdrawal symptoms peak between 48 and 72 hours after the last dose of heroin and subside after about a week. At this time, weakness and depression are pronounced and nausea and vomiting are common. Nevertheless, some chronic addicts have shown persistent withdrawal signs for many months or even years. Heroin addiction is considered as a behavioural state of compulsive drug use and a high tendency to relapse after periods of abstinence. It is generally accepted that compulsive use and relapse are typically associated with the status of heroin craving or heroin hunger that are difficult to define but appear to be powerful motivational significance in the addiction process. The route of administering heroin varies largely and may indicate the degree of seriousness of the individual's addiction. Intravenous administration seems to be the predominant method of heroin use, but recently a shift in heroin use pattern has been found, i.e. from injection to sniffing and smoking. Frequent injections coupled with widespread sharing of syringes increase the risk of contracting HIV, hepatitis B, C and other blood-borne infectious diseases. Long-term use of heroin has also severe medical consequences such as scarred veins, bacterial infections of blood vessels, liver and kidney diseases, and lung complications.

Topics: Administration, Intranasal; Animals; Behavior, Addictive; Chronic Disease; Euphoria; Global Health; Haplorhini; Heroin; Heroin Dependence; Humans; Infusions, Intravenous; Narcotics; Opiate Substitution Treatment; Powders; Recurrence; Severity of Illness Index; Substance Withdrawal Syndrome; Time Factors

Several types of medications have been used for stabilizing heroin users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The present review focuses on the prescription of heroin to heroin-dependent individuals.. To compare heroin maintenance to methadone or other substitution treatments for opioid dependence regarding: efficacy and acceptability, retaining patients in treatment, reducing the use of illicit substances, and improving health and social functioning.. A review of the Cochrane Central Register of Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to 2008), EMBASE (1980 to 2005) and CINAHL until 2005 (on OVID) was conducted. Personal communication with researchers in the field of heroin prescription identified other ongoing trials.. Randomised controlled trials of heroin maintenance treatment (alone or combined with methadone) were compared with any other pharmacological treatment for heroin-dependent individuals.. Two reviewers independently assessed trial quality and extracted data.. Eight studies involving 2007 patients were included. Results show marginal significance in favour of heroin for remaining in treatment until the end of the study (8 studies, N= 2007, RR=1.23, 95%CI=0.96-1.57; heterogeneity P < 0.01). Adverse events are significantly more frequent in the heroin group. Heroin plus methadone prescription for maintenance treatment in adult chronic opioid users who failed previous methadone treatment attempts decreases the use of other illicit substances (3 Studies, N=1289, RR=0.63, 95%CI=0.49, 0.81, heterogeneity P=0.21), and reduces the risk of being incarcerated (2 studies, N=1103, RR=0.64, 95%CI=0.51-0.79, heterogeneity P=0.31). In addition, we also found a marginally significant protective effect of heroin prescription plus methadone for the use of street heroin (3 studies, N=1512, RR=0.70, 95%CI=0.49-1.00, heterogeneity P < 0.01) and for criminal activity (4 studies, N=1377, RR=0.80, 95%CI=0.61-1.04, heterogeneity P=0.31). There was not enough power to detect statistically significant results for the risk of death (5 studies, N=1817, RR=0.77, 95%CI=0.32-1.87, heterogeneity P=0.79).. The available evidence suggests a small added value of heroin prescribed alongside flexible doses of methadone for long-term, treatment-refractory opioid users, considering a decrease in the use of street heroin and other illicit substances, and in the probability of being imprisoned; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment of last resort for people who are currently or have in the past failed maintenance treatment.

Topics: Adult; Crime; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Randomized Controlled Trials as Topic

Heroin addiction may increase the risk of pulmonary involvement. We describe the case of a 23 year-old woman who was admitted to our unit for severe asthma attack non responsive to beta-2-agonists and acute respiratory failure, soon after heroin inhalation. The patient was successfully treated with non invasive positive pressure ventilation. Opiate inhalation can be an asthma trigger and should be considered in the care of patients with poorly controlled asthma and life-threatening asthmatic attacks.

Topics: Administration, Inhalation; Adolescent; Asthma; Female; Heroin; Heroin Dependence; Humans; Young Adult

Heroin craving is a trigger for relapse and dropping out of treatment. Methadone has been the standard medication for the management of heroin craving.. We explored the medication options other than methadone which may have heroin anticraving properties.. To be selected for the review, articles had to include outcome measures of the effect of the studied medication on subjective and/or objective opiate craving and be of the following two types: (1) randomized, controlled, and/or double-blind clinical trials (RCTs) examining the relationship between the studied medication and heroin craving; (2) nonrandomized and observational studies (NRSs) examining the relationship between the studied medication and heroin craving. Thirty-three articles were initially included in the review. Twenty-one were excluded because they did not meet the inclusion criteria. We present the results of 12 articles that met all the inclusion criteria.. Some new medications have been under investigation and seem promising for the treatment of opiate craving. Buprenorphine is the second most studied medication after methadone for its effect on opiate craving. At doses above 8 mg daily, it seems very promising and practical for managing opiate craving in patients receiving long-term opioid maintenance treatment.. In doses higher than 8 mg daily, buprenorphine is an appropriate treatment for opiate craving. More research with rigorous methodology is needed to study the effect of buprenorphine on heroin craving. Also more studies are needed to directly compare buprenorphine and methadone with regard to their effects on heroin craving.

Topics: Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

The objective of this review is to describe self-administration procedures for modeling addiction to cocaine, cannabis and heroin in the human laboratory, the benefits and pitfalls of the approach, and the methodological issues unique to each drug. In addition, the predictive validity of the model for testing treatment medications will be addressed. The results show that all three drugs of abuse are reliably and robustly self-administered by non-treatment-seeking research volunteers. In terms of pharmacotherapies, cocaine use is extraordinarily difficult to disrupt either in the laboratory or in the clinic. A range of medications has been shown to significantly decrease cocaine's subjective effects and craving without decreasing either cocaine self-administration or cocaine abuse by patients. These negative data combined with recent positive findings with modafinil suggest that self-administration procedures are an important intermediary step between pre-clinical and clinical studies. In terms of cannabis, a recent study suggests that medications that improve sleep and mood during cannabis withdrawal decrease the resumption of marijuana self-administration in abstinent volunteers. Clinical data on patients seeking treatment for their marijuana use are needed to validate these laboratory findings. Finally, in contrast to cannabis or cocaine dependence, there are three efficacious Food and Drug Administration-approved medications to treat opioid dependence, all of which decrease both heroin self-administration and subjective effects in the human laboratory. In summary, self-administration procedures provide meaningful behavioral data in a small number of individuals. These studies contribute to our understanding of the variables maintaining cocaine, marijuana and heroin intake, and are important in guiding the development of more effective drug treatment programs.

Topics: Cannabinoids; Cocaine; Cocaine-Related Disorders; Heroin; Heroin Dependence; Humans; Illicit Drugs; Marijuana Abuse; Models, Psychological; Self Administration; Social Environment; Treatment Outcome

Current pharmacotherapies for treating morphine/heroin dependence are designed to substitute or block addiction by targeting the drug itself rather than the brain. The heroin addict is still being exposed to addictive opiates, and consequently may develop tolerance to and experience withdrawal and drug's toxic effects from the treatment with high incidence of relapse to addictive drug consumption. As for other drugs of abuse, an alternative approach for morphine/heroin addiction is an antibody-based antagonism of heroin's brain entry. This review summarizes the literature examining important aspects of neurobiological and pharmacological processes involved in opiate dependence. Thereafter, classical pharmacological interventions for opiate dependence treatment and its major clinical limitations are reviewed. Finally, relevant preclinical studies are examined for comparisons in the design, use, immunogenic profile and efficacy of several models of morphine/heroin vaccine as immunologic interventions on the pharmacokinetics and behavioral of morphine/heroin in the rat as animal model.

Topics: Animals; Antibodies; Heroin; Heroin Dependence; Humans; Morphine; Morphine Dependence; Rats; Secondary Prevention; Vaccines, Conjugate

Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.

Topics: Arousal; Brain; Buprenorphine; Delayed-Action Preparations; Heroin; Heroin Dependence; Humans; Immunocompetence; Methadone; Motivation; Narcotics; Receptors, Opioid; Treatment Outcome

The prescription of heroin (diamorphine) for the management of heroin dependence is a controversial treatment approach that was limited to Britain until the 1990s. Since then a number of countries have embarked upon clinical trials of this approach, and it is currently licensed and available in several European countries. To date, six randomized controlled trials (RCTs) with over 1600 patients and several cohort studies have examined injected (or inhaled) heroin treatment. This article reviews relevant clinical pharmacology, how heroin treatment programmes are delivered, and the evidence regarding safety, efficacy and cost-effectiveness from RCTs. Heroin is usually prescribed in intravenous dosages of 300-500 mg/day, divided in two or three doses. Uncommon but serious side effects include seizures and respiratory depression immediately following injection. Despite methodological shortcomings, RCTs generally indicate that heroin treatment results in a comparable retention, improved general health and psychosocial functioning, and less self-reported illicit heroin use than oral methadone treatment. Cost-effectiveness studies indicate heroin treatment to be more expensive to deliver but to result in savings in the criminal justice sector. There has been debate regarding how heroin treatment should be positioned within the range of treatment approaches for this condition. There is increasing consensus that, in countries that have robust and accessible treatment systems for heroin users, heroin treatment is suited to a minority of heroin users as a second-line treatment for those individuals who do not respond to methadone or buprenorphine treatment delivered under optimal conditions.

Topics: Cost-Benefit Analysis; Heroin; Heroin Dependence; Humans; Narcotics; Outcome Assessment, Health Care; Prescriptions; Randomized Controlled Trials as Topic

This project applies agent-based modeling (ABM) techniques to better understand the operation, organization, and structure of a local heroin market. The simulation detailed was developed using data from an 18-month ethnographic case study. The original research, collected in Denver, CO during the 1990s, represents the historic account of users and dealers who operated in the Larimer area heroin market. Working together, the authors studied the behaviors of customers, private dealers, street-sellers, brokers, and the police, reflecting the core elements pertaining to how the market operated. After evaluating the logical consistency between the data and agent behaviors, simulations scaled-up interactions to observe their aggregated outcomes. While the concept and findings from this study remain experimental, these methods represent a novel way in which to understand illicit drug markets and the dynamic adaptations and outcomes they generate. Extensions of this research perspective, as well as its strengths and limitations, are discussed.

Topics: Anthropology, Cultural; Commerce; Community Mental Health Services; Community-Institutional Relations; Heroin; Heroin Dependence; Humans; Illicit Drugs; Needle-Exchange Programs

Topics: Drug Overdose; Evidence-Based Emergency Medicine; Heroin; Heroin Dependence; Humans; Male; Naloxone; Narcotic Antagonists; Narcotics; Self Administration

In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. Pharmacological studies have consistently identified a number of signalling proteins relevant to morphine-induced tolerance, including the delta-opioid receptor (DOR), protein kinase C (PKC), protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), nitric oxide synthase (NOS), N-methyl-D-aspartate acid glutamate receptors (NMDAR), and regulators of G-signalling (RGS) proteins. Thus, it is feasible that these treatments which diminish morphine tolerance target distinct elements within the same regulatory machinery. In this scheme, the signals originated at the agonist-activated MORs would be recognised by elements such as the NMDARs, which in turn exert a negative feedback on MOR-evoked signalling. This process involves DOR regulation of MORs, MOR-induced activation of NMDARs (probably via the regulation of Src, recruiting PKC and Galpha subunits) and the NMDAR-mediated activation of CaMKII. The active CaMKII promotes the sequestering of morphine-activated Gbetagamma dimers by phosducin-like proteins (PhLP) and of Galpha subunits by RGS proteins and tolerance to opioids like morphine develops. Future efforts to study these phenomena should focus on fitting additional pieces into this puzzle in order to fully define the mechanism underlying the desensitization of MORs in neural cells.

Topics: Animals; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cyclic AMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Drug Tolerance; G-Protein-Coupled Receptor Kinases; Heroin; Heroin Dependence; Humans; Mice; Morphine; Morphine Dependence; Narcotics; Protein Kinase C; Receptors, G-Protein-Coupled; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid, mu; RGS Proteins; Signal Transduction; Substance Withdrawal Syndrome; Young Adult

Topics: Adult; Demography; Drug Overdose; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists; New England; Prevalence; Prisoners; Prisons; Risk Factors

Since the initial Swiss heroin-assisted treatment (HAT) study conducted in the mid-1990s, several other jurisdictions in Europe and North America have implemented HAT trials. All of these studies embrace the same goal-investigating the utility of medical heroin prescribing for problematic opioid users-yet are distinct in various key details. This paper briefly reviews (initiated or completed) studies and their main parameters, including primary research objectives, design, target populations, outcome measures, current status and-where available-key results. We conclude this overview with some final observations on a decade of intensive HAT research in the jurisdictions examined, including the suggestion that there is a mounting onus on the realm of politics to translate the-largely positive-data from completed HAT science into corresponding policy and programming in order to expand effective treatment options for the high-risk population of illicit opioid users.

Topics: Analgesics, Opioid; Canada; Europe; Health Policy; Heroin; Heroin Dependence; Humans; Multicenter Studies as Topic; Politics; Public Opinion; Randomized Controlled Trials as Topic

This paper on drug use and HIV/AIDS in China follows on from the column's May 2005 article on the description of the first methadone maintenance clinic in Beijing. Methadone maintenance clinics and needle exchange programmes are now being implemented in China as a response to the rapid increase in prevalence of HIV/AIDS over the last 10-15 years. It is worth noting that in prior years methadone was available only as for short-term detoxification from opioids and for research purposes. Accordingly, the Department of Health Education and Behavioural Intervention at the National Center for AIDS Prevention and Control in China plans to establish 1,000 methadone replacement clinics within the next 5 years to treat 200,000 heroin-dependent users who are at increased risk of HIV/AIDS. Robert Ali & Rachel HumeniukEditors, Asia Pacific ColumnThe cumulative number of registered drug users in mainland China increased from 70,000 in 1990 to 1.14 million in 2004. Heroin continues to be the most commonly used drug in China; however, polydrug use is popular among heroin users. Sedatives/hypnotics (e.g. triazolam) and other uncontrolled prescription opioids (e.g. pethidine and tramadol) are used commonly in combination with heroin. The majority of drug users (79%) are young people aged between 17 and 35 years and comprise predominantly farmers (30%) and unemployed people (45%). The HIV/AIDS epidemic in China has reached expansion phase (1995-present). It is estimated that the actual number of HIV/AIDS cases reached 840,000, including 80,000 actual AIDS patients, in 2003, with injecting drug users (IDUs) making up the largest proportion of these cases. Although the prevalence rate of HIV/AIDS is only 0.065% in the Chinese population overall, there is potential for an explosive spread of HIV/AIDS if preventative measures are not employed. Supported by the Chinese government and other related international organisations, harm reduction strategies such as methadone maintenance treatment (MMT) and needle-syringe programmes (NSP) have commenced implementation to reduce the risk of HIV infection among heroin users.

Topics: Acquired Immunodeficiency Syndrome; China; Harm Reduction; Heroin; Heroin Dependence; HIV Seropositivity; Humans; Methadone; Needle-Exchange Programs; Substance Abuse, Intravenous

Street-based heroin injectors represent an especially vulnerable population group subject to negative health outcomes and social stigma. Effective clinical treatment and public health intervention for this population requires an understanding of their cultural environment and experiences. Social science theory and methods offer tools to understand the reasons for economic and ethnic disparities that cause individual suffering and stress at the institutional level.. We used a cross-methodological approach that incorporated quantitative, clinical, and ethnographic data collected by two contemporaneous long-term San Francisco studies, one epidemiological and one ethnographic, to explore the impact of ethnicity on street-based heroin-injecting men 45 years of age or older who were self-identified as either African American or white. We triangulated our ethnographic findings by statistically examining 14 relevant epidemiological variables stratified by median age and ethnicity. We observed significant differences in social practices between self-identified African Americans and whites in our ethnographic social network sample with respect to patterns of (1) drug consumption; (2) income generation; (3) social and institutional relationships; and (4) personal health and hygiene. African Americans and whites tended to experience different structural relationships to their shared condition of addiction and poverty. Specifically, this generation of San Francisco injectors grew up as the children of poor rural to urban immigrants in an era (the late 1960s through 1970s) when industrial jobs disappeared and heroin became fashionable. This was also when violent segregated inner city youth gangs proliferated and the federal government initiated its "War on Drugs." African Americans had earlier and more negative contact with law enforcement but maintained long-term ties with their extended families. Most of the whites were expelled from their families when they began engaging in drug-related crime. These historical-structural conditions generated distinct presentations of self. Whites styled themselves as outcasts, defeated by addiction. They professed to be injecting heroin to stave off "dopesickness" rather than to seek pleasure. African Americans, in contrast, cast their physical addiction as an oppositional pursuit of autonomy and pleasure. They considered themselves to be professional outlaws and rejected any appearance of abjection. Many, but not all, of these ethnographic findings were corroborated by our epidemiological data, highlighting the variability of behaviors within ethnic categories.. Bringing quantitative and qualitative methodologies and perspectives into a collaborative dialog among cross-disciplinary researchers highlights the fact that clinical practice must go beyond simple racial or cultural categories. A clinical social science approach provides insights into how sociocultural processes are mediated by historically rooted and institutionally enforced power relations. Recognizing the logical underpinnings of ethnically specific behavioral patterns of street-based injectors is the foundation for cultural competence and for successful clinical relationships. It reduces the risk of suboptimal medical care for an exceptionally vulnerable and challenging patient population. Social science approaches can also help explain larger-scale patterns of health disparities; inform new approaches to structural and institutional-level public health initiatives; and enable clinicians to take more leadership in changing public policies that have negative health consequences.

Topics: Abscess; Anthropology, Cultural; Black or African American; Crime; Heroin; Heroin Dependence; Humans; Income; Injections, Intramuscular; Injections, Subcutaneous; Interpersonal Relations; Law Enforcement; Male; Middle Aged; Narcotics; Prevalence; Prisons; Social Medicine; Social Support; Socialization; Substance Abuse, Intravenous; White People

To describe the eye misalignments that occur during heroin use and heroin detoxification and to give an overview of the management of persisting diplopia (double vision) which results from eye misalignment.. A literature review using Medline and the search terms strabismus, heroin and substance withdrawal syndrome is presented. General management of cases presenting to the ophthalmologist and orthoptist with acute acquired concomitant esotropia is described.. A tendency towards a divergence of the visual axes appears to be present in heroin users, although when present it may not always lead to diplopia. Following detoxification intermittent esotropia or constant esotropia (convergence of the visual axes) can occur; if intermittent the angle tends to be small and diplopia present when viewing distance objects. Occlusion of one eye to eliminate the second image could encourage the development of a constant deviation. The deviation is not caused by a cranial nerve palsy. Constant deviations of this type are classified as 'acute acquired concomitant esotropia'. Relief from the diplopia may be gained by prismatic correction, and the deviation may then resolve spontaneously. Botulinum toxin or surgical intervention may be necessary in cases that do not resolve.. Heroin use may lead to intermittent or constant exotropia and withdrawal may result in intermittent or constant esotropia. Awareness of the mechanism causing this may avoid referral to other specialties (e.g. neurology) and awareness of treatment modalities could encourage patients to seek appropriate help for relief of symptoms.

Topics: Acute Disease; Diplopia; Heroin; Heroin Dependence; Humans; Strabismus; Substance Withdrawal Syndrome

Since the first reports in the late 1960s and early 1970s there have been numerous studies describing the clinical and pathological features of renal diseases associated with chronic parenteral abuse of heroin, cocaine, morphine, amphetamine, and other narcotic and hallucinogenic drugs, including several adulterants. The past 35 years have witnessed an explosive growth in illicit drug use in many parts of the world. Meanwhile, drug addict nephropathy constitutes an important cause of end-stage renal disease. The term heroin-associated nephropathy' includes different morphological findings following chronic drug abuse. Up to now it still remains ambiguous as to whether or not heroin/morphine itself, adulterants, other diseases like hepatitis B and C infection, or HIV, lead to a spectrum of morphologically described heroin-associated' findings in the kidneys. As a measure of prevention it appears that the purity of heroin plays an important role.

Topics: Hepatitis B, Chronic; Hepatitis C, Chronic; Heroin; Heroin Dependence; HIV Infections; Humans; Kidney Diseases; Narcotics

Many medications have been used for stabilizing heroin users: Methadone, Buprenorphine and LAAM. The present review focus on the prescription of heroin to heroin dependents.. To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning.. The Cochrane Central Register of Trials (CENTRAL) issue 1, 2005; MEDLINE 1966-2005, EMBASE 1980-2005 and CINAHL till 2005 (on OVID) were searched. There was no language or publication year restrictions. Many researchers were contacted for information.. Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments for heroin dependents.. The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity.. 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies could not be analysed cumulatively because of heterogeneity of interventions and outcomes. Retention in treatment: no groups difference was found in two studies; one study (N=96) found RR=2.82 (95% CI 1.70-4.68) favouring heroin; one study (N=235) found RR 0.79 (95%CI 0.68-0.90) favouring methadone. Relapse to illegal heroin use (self- reported): in one study people using heroin in treatment was 64% (heroin group)and 59% (methadone group); in the other study the RR of heroin use was 0.33 (95%CI 0.15-0.72) favouring heroin. Criminal offence: one study showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: two studies did not show statistical difference between intervention groups, and two studies considered criminal offence and social functioning as part of a multidomain outcome measure showing improvements among those treated with heroin plus methadone over those on methadone only.. No definitive conclusions about the overall effectiveness of heroin prescription is possible. Results favouring heroin treatment come from studies conducted in countries where easily accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments. The present review contains information about ongoing trials which results will be integrated as soon as available.

Topics: Heroin; Heroin Dependence; Humans; Narcotics; Randomized Controlled Trials as Topic

Repeated exposure to addictive drugs results in long-lasting neuroadaptations in the brain, especially in the mesocorticolimbic system. Within this system, the nucleus accumbens (NAc) plays a major integrative role. As such, the NAc has been shown to be a target of short- and long-lasting drug-induced neuroadaptations at the levels of neurotransmission and cellular morphology. The long-lasting neuroadaptations might depend critically on alterations in gene expression. Recently, we obtained a set of transcripts by means of subtractive hybridization, of which the expression was decreased in the rat NAc shell after long-term extinction of intravenous heroin self-administration. Interestingly, the majority of these transcripts were also down-regulated upon long-term extinction of cocaine self-administration. Using the yoked-control operant paradigm, it was shown that non-contingent administration of these drugs resulted in a totally different gene expression profile. However, in the rat NAc core, both self-administration and non-contingent heroin administration induced a qualitatively similar expression profile. Hence, cognitive processes associated with drug self-administration seem to direct the long-term genomic responses in the NAc shell, whereas the NAc core might primarily mediate the persistent pharmacological effects of addictive drugs (including Pavlovian conditioning).

Topics: Adaptation, Physiological; DNA, Complementary; Drug Administration Routes; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Heroin; Heroin Dependence; Humans; Hybridization, Genetic; Nerve Tissue Proteins; Nucleus Accumbens; Synaptic Transmission; Time Factors

To determine the cost utility of medical co-prescription of heroin compared with methadone maintenance treatment for chronic, treatment resistant heroin addicts.. Cost utility analysis of two pooled open label randomised controlled trials.. Methadone maintenance programmes in six cities in the Netherlands.. 430 heroin addicts.. Inhalable or injectable heroin prescribed over 12 months. Methadone (maximum 150 mg a day) plus heroin (maximum 1000 mg a day) compared with methadone alone (maximum 150 mg a day). Psychosocial treatment was offered throughout.. One year costs estimated from a societal perspective. Quality adjusted life years (QALYs) based on responses to the EuroQol EQ-5D at baseline and during the treatment period.. Co-prescription of heroin was associated with 0.058 more QALYs per patient per year (95% confidence interval 0.016 to 0.099) and a mean saving of 12,793 euros (8793 pounds sterling, 16,122 dollars) (1083 to 25,229 euros) per patient per year. The higher programme costs (16 222 euros; lower 95% confidence limit 15,084 euros) were compensated for by lower costs of law enforcement (- 4129 euros; upper 95% confidence limit - 486 euros) and damage to victims of crime (- 25,374 euros; upper 95% confidence limit - 16,625 euros). The results were robust for the use of national EQ-5D tariffs and for the exclusion of the initial implementation costs of heroin treatment. Completion of treatment is essential; having participated in any abstinence treatment in the past is not.. Co-prescription of heroin is cost effective compared with treatment with methadone alone for chronic, treatment resistant heroin addicts.

Topics: Administration, Inhalation; Adult; Chronic Disease; Cost of Illness; Cost-Benefit Analysis; Crime; Drug Resistance; Drug Therapy, Combination; Female; Health Resources; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Methadone; Multicenter Studies as Topic; Narcotics; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome

Heroin prescription (HP) to treat severe heroin dependence has been available to few patients in the UK for several decades with limited, but generally favourable, evaluation. In the last decade, large trials have been reported from two countries, are presently underway in three other countries and under consideration in several other countries. The standard pharmacological treatments for heroin dependence, methadone and buprenorphine, attract and retain many more drug users than other pharmacological or nonpharmacological treatments and are strongly supported by evidence of efficacy, effectiveness, safety and cost effectiveness. On present evidence, HP is feasible and safe with limited, but increasing, evidence of efficacy and effectiveness. Although HP is more expensive than methadone, there is some evidence of cost effectiveness. HP is, at present, only considered a therapeutic option for a small minority of treatment refractory, severely heroin-dependent persons in developed countries with comprehensive treatment systems.

Topics: Clinical Trials as Topic; Cost-Benefit Analysis; Heroin; Heroin Dependence; Humans; Narcotics; Practice Patterns, Physicians'; Safety

A spongiform leucoencephalopathy sometimes develops as a result of inhaling illicit heroin as well as due to carbon monoxide-intoxication. Clinically psychiatric symptoms precede a neurological deterioration. Some patients die. After a brief description of several epidemiological and historical-cultural aspects regarding the smoking of opiates, the typical neuroradiological signs such as hypodensity of the white matter in CCT and signal alterations in MRT, and neuropathological sequelae such as intramyelinic vacuolisation are listed. Pathophysiologically an edema of the white matter in the beginning is suspected. Second, a dysfunction of the mitochondria is addressed relying on the particular metabolism of the oligodendrocytes. Since smoking of heroin is an increasingly preferred way of application in all continents and therapeutic options are still lacking, the need of further explanation of the underlying processes is stressed.

Topics: Administration, Inhalation; Brain; Brain Diseases; Carbon Monoxide Poisoning; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed

The use of cocaine by heroin-dependent individuals, or by patients in methadone or buprenorphine maintenance treatment, is substantial and has negative consequences on health, social adjustment and outcome of opioid-addiction treatment. The pharmacological reasons for cocaine use in opioid-dependent individuals, however, are poorly understood and little is known about the patterns of heroin and cocaine co-use. We reviewed anecdotal evidence suggesting that cocaine is co-used with opioid drugs in a variety of different patterns, to achieve different goals. Clinical and preclinical experimental evidence indicates that the simultaneous administration of cocaine and heroin (i.e. 'speedball') does not induce a novel set of subjective effects, nor is it more reinforcing than either drug alone, especially when the doses of heroin and cocaine are high. There is mixed evidence that the subjective effects of cocaine are enhanced in individuals dependent on opioids, although it is clear that cocaine can alleviate the severity of symptoms of withdrawal from opioids. We also reviewed preclinical studies investigating possible neurobiological interactions between opioids and cocaine, but the results of these studies have been difficult to interpret mainly because the neurochemical mechanisms mediating the motivational effects of cocaine are modified by dependence on, and withdrawal from, opioid drugs. Our analysis encourages further systematic investigation of cocaine use patterns among opioid-dependent individuals and in laboratory animals. Once clearly identified, pharmacological and neuroanatomical methods can be employed in self-administering laboratory animals to uncover the neurobiological correlates of specific patterns of co-use.

Topics: Central Nervous System; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Heroin; Heroin Dependence; Humans; Narcotics

Topics: Analgesics, Opioid; Drug Overdose; Heroin; Heroin Dependence; Humans; Methadone; Naloxone; Narcotic Antagonists; Patient Education as Topic

Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin.. To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning.. The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information.. Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments.. The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity.. 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only.. No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.

Topics: Heroin; Heroin Dependence; Humans; Narcotics; Randomized Controlled Trials as Topic

This article discusses the use and distribution of heroin in New York City, both historically and especially currently. Data on the current situation derive in large measure from the Heroin Project, a recently completed five-year ethnographic study of heroin in New York City funded by the National Institute on Drug Abuse. Findings about the new, young heroin user, particularly in regard to demographic characteristics, patterns of use, modes of ingestion, and involvement in crime, and some of the ways in which the new user is similar and different from the "old time" heroin user are presented. In addition changes in the New York City heroin markets over the years are discussed. We note the effectiveness of methadone maintenance treatment in terms of its impact on heroin-related crime, make suggestions as to how methadone treatment could be expanded, and review current heroin policy and the War on Drugs, with a focus on the New York State Rockefeller drug laws and the need for policy reform in this area.

Topics: Analgesics, Opioid; Drug and Narcotic Control; Heroin; Heroin Dependence; Humans; Illicit Drugs; Methadone; New York City; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Urban Health

Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin.. To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning.. The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information.. Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments.. The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity.. 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only.. No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.

Topics: Heroin; Heroin Dependence; Humans; Narcotics; Randomized Controlled Trials as Topic

In this Harm Reduction Digest Paul Dietze and John Fitzgerald provide another possible way of understanding what has come to be referred to as Australia's heroin 'drought'. They examine evidence from Melbourne, Victoria and suggest that the apparent downturn in heroin availability in 2000 may, in part, be the result of an end of a heroin 'glut' and that perceptions of this phenomenon may be coloured by the development of more sophisticated indicators of the heroin market. They conclude with claims that the reasons for the reduction in drug consumption and adverse health outcomes, such as those attributed to interdiction, are thus premature

Topics: Heroin; Heroin Dependence; Humans; South Australia

The objective of this article is to review data from studies that used a reinstatement model in rats to elucidate the neural mechanisms underlying relapse to heroin and cocaine seeking induced by exposure to the self-administered drug (drug priming), conditioned drug cues, and stressors. These factors were reported to contribute to relapse to drug use in humans following prolonged abstinence periods. In the reinstatement model, the ability of acute exposure to drug or nondrug stimuli to reinstate drug seeking is determined following training for drug self-administration and subsequent extinction of the drug-reinforced behavior. We will review studies in which pharmacological agents were injected systemically or intracranially to block (or mimic) reinstatement by drug priming, drug cues, and stressors. We also will review studies in which brain lesions, in vivo microdialysis and electrochemistry, and gene expression methods were used to map brain sites involved in relapse to drug seeking. Subsequently, we will discuss theoretical issues related to the processes underlying relapse to drugs and address methodological issues in studies on reinstatement of drug seeking. Finally, the implications of the findings from the studies reviewed for addiction theories and treatment will be discussed. The main conclusion of this review is that the neuronal mechanisms involved in relapse to heroin and cocaine seeking induced by drug priming, drug cues, and stressors are to a large degree dissociable. The data reviewed also suggest that the neuronal events mediating drug-induced reinstatement are to some degree dissociable from those mediating drug reinforcement.

Topics: Animals; Behavior, Animal; Cocaine; Cocaine-Related Disorders; Cues; Extinction, Psychological; Heroin; Heroin Dependence; Rats; Recurrence; Self Administration; Stress, Psychological

Topics: Drug Prescriptions; Heroin; Heroin Dependence; Humans; Methadone; Netherlands; Substance Abuse, Intravenous

Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. While significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; however, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.

Topics: Adolescent; Adult; Age Factors; Cognition Disorders; Drug Interactions; Drug Tolerance; Female; Hepatitis C, Chronic; Heroin; Heroin Dependence; Humans; Male; Pneumonia, Bacterial; Respiration; Respiratory Insufficiency; Risk Factors; Risk-Taking; Sex Factors; Smoking

In 1994, a new project dealing with the treatment of heroin dependency was introduced in Switzerland. A group of heavy opiate addicts, who had failed in previous medical therapies, received heroin by prescription, supported by health and social services. The admission criteria to this treatment are summarized as the main results of this project: physical and mental health of the addicts improved on average during treatment, an improvement also took place in their social reintegration, a significant decrease in consumption of illegal drugs took place and illegal activities declined massively. The proportion of patients who continued the treatment in a time period of 12 months was held at 76%. Comparison of the treatment costs with the economic benefits shows that there is a total benefit per patient and per day of 26 US dollars. Further drug related political decisions in Switzerland as well as the assessments of the International Narcotics Control Board (INCB) of the United Nations to this project will be reported and discussed.

Topics: Adult; Chronic Disease; Heroin; Heroin Dependence; Humans; Social Support; Switzerland

We report five cases of status asthmaticus (four requiring mechanical ventilation) that were triggered by inhaled heroin and review the pertinent literature. These cases share common features of sudden and severe asthma exacerbations temporally related to heroin use, stress the importance of considering illicit drug use in like cases, and call attention to a public health issue.

Topics: Adult; Female; Heroin; Heroin Dependence; Humans; Intubation, Intratracheal; Male; Narcotics; Positive-Pressure Respiration; Status Asthmaticus

THREE CATEGORIES OF COMPLICATIONS: Heroine and cocaine are the main drugs used by injecting drug-users (IDU) in France. There are three categories of complications associated with intravenous drug abuse: effects related to drug toxicity, effects associated with the administration route, and effects associated with social implications of drug-dependence. OTHER HEALTH PROBLEMS: The impact of HIV infection among IDU, particularly in southern Europe, has led to renewed interest in the other health problems raised by this population. A review of recent literature shows that cocaine toxicity is better understood than heroine toxicity. In addition, intravenous drug abuse can lead to a whole series of disease states related to trauma or infection.

Topics: Cocaine; Cocaine-Related Disorders; Heroin; Heroin Dependence; Humans; Risk Factors; Substance Abuse, Intravenous

The initial assessment and subsequent monitoring of compliance in methadone treatment programmes are excessively reliant on the accuracy of self-report from opiate addicts themselves. Given the central position of methadone treatment in the therapeutic options currently available and with the increasing number of opiate addicts requiring treatment, improved methods of judging optimal methadone treatment are required. This paper explores the possible future options for assessing the adequacy of methadone prescribing from the analysis of methadone levels in urine, blood, hair and saliva. The particular promise of plasma therapeutic drug monitoring for methadone is explored, accompanied by an account of the state of the art at the time of writing.

Topics: Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Patient Compliance; Saliva; Treatment Outcome

Acute heroin overdose is a common daily experience in the urban and suburban United States and accounts for many preventable deaths. Heroin acts as a pro-drug that allows rapid and complete central nervous system absorption; this accounts for the drug's euphoric and toxic effects. The heroin overdose syndrome (sensitivity for diagnosing heroin overdose, 92%; specificity, 76%) consists of abnormal mental status, substantially decreased respiration, and miotic pupils. The response of naloxone does not improve the sensitivity of this diagnosis. Most overdoses occur at home in the company of others and are more common in the setting of other drugs. Heroin-related deaths are strongly associated with use of alcohol or other drugs. Patients with clinically significant respiratory compromise need treatment, which includes airway management and intravenous or subcutaneous naloxone. Hospital observation for several hours is necessary for recurrence of hypoventilation or other complications. About 3% to 7% of treated patients require hospital admission for pneumonia, noncardiogenic pulmonary edema, or other complications. Methadone maintenance is an effective preventive measure, and others strategies should be studied.

Topics: Drug Overdose; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists; United States

This article includes a summary and critique of methodological limitations of the peer-reviewed studies of developmental outcome during the first 2 years in children prenatally exposed to the most commonly used drugs of abuse: tobacco, alcohol, marijuana, heroin/methadone, and cocaine. Reported effects vary by specific drug or drug combinations and amount and timing of exposure; however, few thresholds have been established. Drug effects also appear to be exacerbated in children with multiple risks, including poverty, and nonoptimal caregiving environments. Although prenatal exposure to any one drug cannot reliably predict the outcome of an individual child, it may be a marker for an array of variables that can impact development. Appropriate intervention strategies require future research that determines which factors place exposed children at risk and which are protective for optimal development.

Topics: Alcoholism; Child Abuse; Child Development; Child, Preschool; Cocaine; Cocaine-Related Disorders; Ethanol; Female; Heroin; Heroin Dependence; Humans; Infant; Infant, Newborn; Marijuana Abuse; Methadone; Nicotine; Poverty; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk Factors; Smoking; Substance-Related Disorders

Topics: Drug Prescriptions; Heroin; Heroin Dependence; Humans; Spain; Substance Abuse, Intravenous; United Kingdom

A 17-year-old previously healthy girl with profound circulatory shock following a heroin overdose is reported. Except for opiates no other substances and specifically no cocaine were found in the blood and urine samples. Even though the mechanism of shock is not completely understood, severe depression of left ventricular contractility seems to be the predominant reason. Acute right heart failure with decreased pulmonary capillary wedge pressure and arterial vasodilatation resulting in maldistribution of cardiac output cannot be ruled out as possible contributing factors. The shock was successfully reversed with volume loading and a high dose of dobutamine. The recovery was uneventful and the patient was discharged with normal cardiac function.

Topics: Adolescent; Combined Modality Therapy; Drug Overdose; Emergencies; Female; Heroin; Heroin Dependence; Humans; Shock

Gas in the hepatic portal venous system has been noted to be a complication of a wide range of intra-abdominal catastrophes that involve damage to bowel mucosa. We describe a patient who, after a seizure, was found to have portal venous gas on sonography and CT. The search for other possible causes revealed negative results. This case demonstrates a rare cause of hepatic portal venous gas that is self-resolving and clinically benign.

Topics: Adult; Embolism, Air; Heroin; Heroin Dependence; Humans; Male; Portal Vein; Seizures; Substance Withdrawal Syndrome; Tomography, X-Ray Computed; Ultrasonography

Overdose deaths are a major contributor to excess mortality among heroin users. It has been proposed that opioid overdose morbidity and mortality could be reduced substantially by distributing the opioid antagonist naloxone to heroin users. The ethical issues raised by this proposal are evaluated from a utilitarian perspective. The potential advantages of naloxone distribution include the increased chance of comatose opioid users being quickly resuscitated by others present at the time of an overdose, naloxone's safety and its lack of abuse potential. The main problems raised by the proposal are: the medico-legal complications of medical practitioners prescribing a drug that is most likely to be administered to and by people other than the one for whom it is prescribed; the economic costs of distributing naloxone sufficiently widely to have an impact on overdose morbidity and mortality; and the potentially greater cost-effectiveness of simpler educational interventions. Given the possible benefits of naloxone distribution, it may be worthwhile considering a controlled trial of naloxone distribution to high-risk heroin users.

Topics: Decision Making; Drug Costs; Drug Overdose; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists

An admission cohort of 296 Australian methadone maintenance patients was followed over 15 years. The relative risks of death in and out of maintenance were calculated for two age groups, 20-29 and 30-39 years. Heroin addicts in both age groups were one-quarter as likely to die while receiving methadone maintenance as addicts not in treatment. This is because they were significantly less likely to die by heroin overdose or suicide while in maintenance. Methadone maintenance had no measurable effect on the risk of death through nonheroin overdose, violence or trauma, or natural causes. A meta-analysis showed the reduction in overall mortality was consistent with the results of cohort studies conducted in the United States, Sweden, and Germany. The combined results of the five studies again indicated that methadone maintenance reduced addicts' risk of death to a quarter, RR 0.25 (95% CI 0.19 to 0.33).

Topics: Accidents; Adult; Cohort Studies; Drug Overdose; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Methadone; New South Wales; Risk; Suicide; Suicide Prevention

The current paper examines critically the literature on deaths attributed to heroin overdose, and examines the characteristics and circumstances of such deaths. In particular, the dominance of the widely held belief that heroin-related fatalities are a consequence of overdose is challenged. Deaths attributed to overdose represented in the literature are typically older, heroin-dependent males not in drug treatment at the time of death. Fatalities involving only heroin appear to form a minority of overdose occasions, the presence of other drugs (primarily central nervous system depressants such as alcohol and benzodiazepines) being commonly detected at autopsy. Furthermore, deaths attributed to overdose are likely to have morphine levels no higher than those who survive, or heroin users who die from other causes. It is concluded that the term overdose is, in many cases, a misleading term, since it implies the same mechanism of death in all cases, an implication that is neither clinically useful nor consistent with published data. Implications for the prevention of heroin-related deaths are discussed.

Topics: Adult; Aged; Cause of Death; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Incidence; Male; Middle Aged; New South Wales; Psychotropic Drugs

This paper reviewed heroin use data from the US government's epidemiologic monitoring system for substance abuse. The monitoring system has multiple components, i.e., the Drug Abuse Warning Network of reporting emergency rooms (9), annual surveys of high school and post-high school youth (3, 4), annual National Household Surveys of Substance Abuse (7, 8, 50), Drug Use Forecasting (51), the Community Epidemiology Work Group (52), and law enforcement systems not reviewed here. These monitoring systems should identify any major increase in heroin incidence in this country relatively early. This is important, because the early stages of heroin epidemics are often hidden from society, and the epidemics are already full-blown by the time health and other agencies become aware of the size of the affected population and are required to respond. The hidden or underground nature of heroin epidemics is caused by 1) the need of each user to hide an illegal activity and 2) the delay between the time when heroin is first used and the onset of physical dependence and other adverse consequences, which bring new heroin addicts to the attention of treatment and enforcement systems. Despite an epidemiologic surveillance system which should rapidly identify large-scale heroin spread in this country, our treatment and law enforcement systems are not organized to respond rapidly to contain an epidemic. Substance abuse treatment services are not structured for rapid expansion and contraction based on fluctuating need. Apart from HIV prevention programs, we do not have outreach teams attached to treatment programs that could quickly identify local outbreaks and involve new heroin abusers in treatment (10).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Cross-Sectional Studies; Disease Outbreaks; Drug and Narcotic Control; Female; Heroin; Heroin Dependence; HIV Infections; Humans; Incidence; Male; Middle Aged; Population Surveillance; Risk Factors; Substance Abuse, Intravenous; United States

Urinalysis can be used as an objective criterion for monitoring the outcome of a treatment program or a clinical trial. Important factors to consider when implementing a drug testing program include standardization of assay technology and cutoffs between participating centers and selection of identical testing schedules. Also, it is vitally important to minimize the amount of safe time (time that drug use can go undetected) occurring in a testing schedule. The detection times for cocaine and heroin have been shown to vary with selection of cutoff and with the drug dose. Obviously, the selection of cutoffs is under program control, whereas the amount of illicit drug use is under subject control. Fortunately, changes in the illicit drug dose by the subject demonstrate a log-linear relationship to detection time. Hence, a higher drug dose by the subject only extends the detection time slightly (and improves the probability of detection) without greatly increasing the risks of drug carryover from one urine test to another. The most efficient testing schedule for judging the outcome of clinical trials for cocaine and heroin appears to be a 3-days-a-week schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday). When different schedules were challenged by simulating random times at which cocaine use might occur during the week, the 3-days-per-week schedule was the most efficient without the risk of carryover. The 3-days-per-week schedule also performed better than 1-day-per-week when multiple random drug use was simulated. Overall, the 3-days-per-week testing schedule with specified assay technology and cutoffs was the best compromise for maximizing detection of drug use, minimizing carryover, and providing a standardized methodology for outcome comparison between programs.

Topics: Clinical Trials as Topic; Cocaine; Data Interpretation, Statistical; Heroin; Heroin Dependence; Humans; Substance Abuse Detection; Substance-Related Disorders

Topics: Chromatography, Gas; Heroin; Heroin Dependence; Humans; Immunoenzyme Techniques; Mass Spectrometry; Methadone; Narcotics; Opium

Topics: Antigens, CD; CD4-CD8 Ratio; Cocaine; Drug Interactions; Ethanol; Gene Expression Regulation; Heroin; Heroin Dependence; Humans; Immune System; Morphine; Rosette Formation; Substance-Related Disorders; T-Lymphocyte Subsets

The spectrum of neurological complications associated with heroin addiction has changed in the past six years because of the progressive knowledge of the neurological complications related to HIV infection. We reviewed 48 heroin addicts with neurological complications and 452 heroin overdose who were seen in the Emergency Unit of our hospital during 1988 and the publications since 1967. Regarding the overdose we present the results of a prospective study leading to determine the causes. We emphasize the relationship with the level of total morphine in serum, instead of conjugate morphine, and with the presence of high levels of benzodiazepines found in the plasma rather than an hypothetic hypersensitivity phenomenon. We resume the neurological complications related with heroin addiction: spongiform leukoencephalopathy, epileptic seizures, stroke, transverse myelopathy and neuromuscular complications such mononeuropathy, plexopathy, acute inflammatory demyelinating polyradiculoneuropathy, rhabdomyolysis, fibrosing myopathy, musculoskeletal syndrome and acute bacterial myopathy. Some of such complications (i.e. transverse myelitis, polyradiculoneuropathy, leucoencephalopathy) must rise the suspicion of an HIV infection. Likewise, in patients assisted for overdosage we believe it's necessary rule out myoglobinuria by means of CPK serum levels and detection of urine hematic pigments without red blood cels in the urine sediment, in order to prevent and treat the renal failure. We report the results of muscular biopsy found in the musculoskeletal syndrome, which are similar to those found in alcoholic myopathy. Finally, we describe the clinical and diagnostic aspects in an unusually neuromuscular complication: the acute bacterial myopathy.

Topics: Cerebrovascular Disorders; Coma; Drug Overdose; Epilepsy; Heroin; Heroin Dependence; Humans; Leukoencephalopathy, Progressive Multifocal; Muscular Diseases; Myelitis, Transverse; Nervous System Diseases; Peripheral Nervous System Diseases

Naltrexone is a long acting competitive antagonist at opioid receptors which blocks the subjective and objective responses produced by intravenous opioid challenge. It is suitable for oral administration, and has been studied as an adjunct for use in opioid addiction management programmes. In non-comparative clinical trials involving detoxified patients, oral naltrexone reduced heroin craving and between 23 and 62% of patients remained in treatment after 3 to 4 weeks. However, in two studies 32 to 58% of patients who continued in treatment were opioid-free between 6 and 12 months after stopping naltrexone. As might be expected studies involving highly motivated patients have shown this type of patient group to achieve greater treatment success rates during naltrexone therapy, and remain opioid-free longer than other groups of apparently less motivated patients. In addition, when naltrexone is combined with family support, psychotherapy and counselling, patients are more likely to remain opioid-free. Naltrexone produces a low incidence of side effects, with gastrointestinal effects being the most commonly reported symptoms. Thus, despite the overall high attrition rates from trials, in selected patient groups and in combination with appropriate support mechanisms and psychotherapy, naltrexone represents a useful adjunct for the maintenance of abstinence in the detoxified opioid addict.

Topics: Animals; Heroin; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Receptors, Opioid

Medical complications of heroin overdose and the diseases of addicts play an increasingly important role in the daily routine of hospital medical departments. The percentage of drug-related admissions to the Medical Clinic of the University Hospital, Zürich, increased from 0.18% to 4.45% between 1972 and 1983. During this 12-year period, 492 patients were admitted 569 times because of heroin overdose or intoxications combined with other drugs, and 191 drug addicts were hospitalized 226 times for a variety of medical problems. Certain complications, such as heroin pulmonary edema and talc granulomas of the lung, occur only in parenteral drug addiction. Other diseases such as right heart endocarditis, Candida-endophthalmitis, septic arthritis and osteomyelitis are almost exclusively observed in intravenous drug abusers. Sexually transmitted infections and hepatitis B are frequently diagnosed in addicts.

Topics: Adolescent; Adult; Age Factors; Arthritis, Infectious; Candidiasis; Cardiovascular Diseases; Endocarditis, Bacterial; Female; Hepatitis, Viral, Human; Heroin; Heroin Dependence; Humans; Length of Stay; Lung Diseases; Male; Nervous System Diseases; Osteomyelitis; Pulmonary Edema; Rhabdomyolysis; Sex Factors; Sexually Transmitted Diseases; Skin Diseases; Switzerland

Recent clinical observations and psychiatric diagnostic findings of drug-dependent individuals suggest that they are predisposed to addiction because they suffer with painful affect states and related psychiatric disorders. The drugs that addicts select are not chosen randomly. Their drug of choice is the result of an interaction between the psychopharmacologic action of the drug and the dominant painful feelings with which they struggle. Narcotic addicts prefer opiates because of their powerful muting action on the disorganizing and threatening affects of rage and aggression. Cocaine has its appeal because of its ability to relieve distress associated with depression, hypomania, and hyperactivity.

Topics: Adult; Affective Symptoms; Aggression; Bipolar Disorder; Choice Behavior; Cocaine; Depressive Disorder; Heroin; Heroin Dependence; Humans; Male; Mental Disorders; Narcotics; Opioid-Related Disorders; Psychiatric Status Rating Scales; Psychoanalytic Theory; Rage; Self Medication

Topics: Adolescent; Adult; Anesthesia; Emergency Medical Services; Female; Heroin; Heroin Dependence; Hospitalization; Hospitals, General; Humans; Infant, Newborn; Patient Admission; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Surgical Procedures, Operative

The causes of heroin addiction have been studied and debated, and many theories have evolved. This article reviews the extensive literature on the subject and groups the material under the categories of Psychological, Pharmacological, Genetic, Socilogical, Social Protest, The Family, and Stepping Stone theories.

Topics: Anomie; Genetics; Heroin; Heroin Dependence; Humans; Mental Disorders; Oral Stage; Personality; Psychoanalytic Theory; Social Behavior; Social Conditions; Social Environment

Topics: Analgesics; Analgesics, Opioid; Clinical Trials as Topic; Drug Administration Schedule; Drug Evaluation; Drug Tolerance; Heroin; Heroin Dependence; Humans; Kinetics; Methadone; Methadyl Acetate; Morphine; Morphine Dependence; Patient Dropouts; Substance Withdrawal Syndrome; Time Factors

Topics: Clinical Trials as Topic; Conditioning, Psychological; Cyclazocine; Drug Evaluation; Euphoria; Heroin; Heroin Dependence; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Research; Research Support as Topic; United States; United States Substance Abuse and Mental Health Services Administration

Topics: Alcoholism; Ambulatory Care; Amphetamines; Aversive Therapy; Barbiturates; Cannabis; Follow-Up Studies; Hallucinogens; Heroin; Heroin Dependence; Humans; Legislation, Drug; Methadone; Smoking; Substance-Related Disorders; United Kingdom

Topics: Abscess; Adult; Animals; Autopsy; Blindness; Brain Diseases; Cerebrovascular Disorders; Endocarditis; Haplorhini; Hepatitis A; Heroin; Heroin Dependence; Humans; Male; Muscular Diseases; Myelitis, Transverse; Nervous System Diseases; New York City; Peripheral Nervous System Diseases; Quinine; Substance-Related Disorders; Tetanus

Topics: Crime; Drug and Narcotic Control; Ethics, Medical; Government Agencies; Heroin; Heroin Dependence; Humans; Legislation, Drug; Politics; Public Opinion; Research; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom; United States

Cost-effectiveness analysis of two 12-week contingency management (CM) schedules targeting heroin abstinence or attendance at weekly keyworker appointments for opioid agonist treatment compared with treatment as usual (TAU).. A cost-effectiveness analysis was conducted alongside a cluster randomized trial of 552 patients from 34 clusters (drug treatment clinics) randomly allocated 1:1:1 to opioid agonist treatment plus weekly keyworker appointments with (1) CM targeted at heroin abstinence (CM abstinence), (2) CM targeted at on-time attendance at weekly appointments (CM attendance), or (3) no CM (TAU). The primary cost-effectiveness analysis at 24 weeks after randomization took a societal cost perspective with effects measured in heroin-negative urine samples.. At 24 weeks, mean differences in weekly heroin-negative urine results compared with TAU were 0.252 (95% confidence interval [CI] -0.397 to 0.901) for CM abstinence and 0.089 (95% CI -0.223 to 0.402) for CM attendance. Mean differences in costs were £2562 (95% CI £32-£5092) for CM abstinence and £317 (95% CI -£882 to £1518) for CM attendance. Incremental cost-effectiveness ratios were £10 167 per additional heroin-free urine for CM abstinence and £3562 for CM attendance with low probabilities of cost-effectiveness of 3.5% and 36%, respectively. Results were sensitive to timing of follow-up for CM attendance, which dominated TAU (better outcomes, lower costs) at 12 weeks, with an 88.4% probability of being cost-effective. Probability of cost-effectiveness remained low for CM abstinence (8.6%).. Financial incentives targeted toward heroin abstinence and treatment attendance were not cost-effective over the 24-week follow-up. Nevertheless, CM attendance was cost-effective over the treatment period (12 weeks), when participants were receiving keyworker appointments and incentives.

Topics: Analgesics, Opioid; Cost-Benefit Analysis; Heroin; Heroin Dependence; Humans; Motivation

Transcranial direct current stimulation (tDCS) has been demonstrated to modulate neural activity and related brain functions. In clinical studies, tDCS has been shown to reduce craving in various substance use disorders including cocaine, heroin and nicotine. Our previous report suggested that cathodal tDCS on the frontal-parietal-temporal (FPT) brain areas reduced cigarette consumption in moderate smokers. However, whether it is effective in smokers with history of drug use is unknown. This study investigated the effects of bilateral FPT areas cathodal tDCS on smokers with history of heroin use. 22 abstinent heroin users were recruited and randomly assigned to sham group and tDCS group. The sham group received 30 s tDCS treatment and tDCS group received normal tDCS (one trial of 20 min, 1 mA, cathodal electrodes were placed bilaterally on the FPT areas). The average of daily cigarettes consumption was recorded for the week before the tDCS and the following day after tDCS. In addition, pupil light reflex was measured right before and after tDCS treatment. One trial of tDCS stimulation significantly reduced daily cigarette consumption in smokers who had heroin use history. This reducing effect was also observed in heavy smokers. In addition, this effect on cigarette consumption lasted at least 48 h after the stimulation. Furthermore, it has been shown that opiates decrease pupillary size in humans, we found detectable changes of the dynamic pupil light reflex after bilateral tDCS stimulation. These findings suggest that FPT cathodal tDCS may be an effective approach to reduce cigarette craving in heroin users.

Topics: Brain; Double-Blind Method; Heroin; Heroin Dependence; Humans; Prefrontal Cortex; Tobacco Products; Transcranial Direct Current Stimulation

Impaired behavioral inhibition is a critical factor in drug addiction and relapse. Repetitive transcranial magnetic stimulation (rTMS) reduces the craving of heroin-addicted individuals for drug-related cues. However, it is unclear whether this technique also improves impaired behavioral inhibition and how improved behavioral inhibition affects craving.. The intermittent theta-burst stimulation (iTBS) has been recently shown to be non-inferior relative to rTMS for depression. Here, we aim to investigate the effect of iTBS on heroin-addicted individuals' behavioral inhibition and cue-induced craving and the relationship between the alteration of behavioral inhibition and craving.. 42 of 56 initially recruited individuals with the heroin-use disorder in the abstinent-course treatment were randomized to undergo active or sham iTBS to the left dorsolateral prefrontal cortex and received three daily iTBS treatments for 10 consecutive days. We measured participants' performance during a two-choice oddball task (80% standard and 20% deviant trials) and heroin-related cue-induced craving before and immediately after treatment.. The group that received active iTBS showed significantly improved two-choice oddball task performance after 10 days of intervention compared to both pre-intervention and the group who received sham iTBS. Similarly, a significant reduction in cue-induced craving was observed after following the intervention in the active iTBS group but not the sham iTBS group. The moderation model indicated that iTBS categories play a significant moderating role in the relationship between accuracy cost changing and altered cue-induced craving.. The iTBS treatment protocol positively affects behavioral inhibition in patients with heroin addiction. Improvements in behavioral inhibition can substantially reduce craving.

Topics: Craving; Cues; Heroin; Heroin Dependence; Humans; Prefrontal Cortex; Theta Rhythm; Transcranial Magnetic Stimulation

To review the safety profile of injectable hydromorphone and diacetylmorphine and explore if adverse events (AEs) or serious adverse events (SAEs) were associated with dose and patterns of attendance.. This was a non-inferiority randomized double-blind controlled trial (Vancouver, Canada) testing hydromorphone (n=100) and diacetylmorphine (n=102) for the treatment of severe opioid use disorder. Medications were delivered under the supervision of trained Registered Nurses up to three times daily. AEs were described using MedDRA codes.. Most common related AEs included immediate post-injection reaction or injection site pruritus reactions, somnolence and opioid overdoses. Adjusted analysis indicated that participants in the hydromorphone group were less likely to have any related AE or SAE compared to the diacetylmorphine group. Related somnolence and opioid overdose events were distributed throughout the six months treatment period. In the diacetylmorphine group, five of the eleven related SAE opioid overdoses (requiring naloxone) occurred in the first 30days since most recent treatment initiation. Analysis of somnolence and opioid overdose (AEs and SAEs) event rates by received dose suggested a non-linear relationship. However, in the diacetylmorphine group higher event rates per person days were recorded at lower doses.. When injectable hydromorphone and diacetylmorphine are individually dosed and monitored, their opioid-related side effects, including potential fatal overdoses, are safely mitigated and treated by health care providers. In the midst of an opioid overdose epidemic, injectable options are timely to reach a very important minority of people who inject street opioids and are not attracted to other treatments.

Topics: Adult; Analgesics, Opioid; Canada; Double-Blind Method; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Hydromorphone; Injections; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Self Administration; Severity of Illness Index; Time Factors

The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro- opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.

Topics: Administration, Intravenous; Adult; Cross-Over Studies; DNA Methylation; Emotions; Epigenesis, Genetic; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Pro-Opiomelanocortin; Promoter Regions, Genetic; Receptors, Glucocorticoid; Time Factors; Treatment Outcome

For patients hospitalized on inpatient detoxification units, reducing negative symptoms such as withdrawal and craving is a key treatment area. Although lyric analysis is a commonly utilized music therapy intervention for clients in substance abuse rehabilitation, there is a lack of randomized controlled music therapy studies systematically investigating how lyric analysis interventions can affect patients on a detoxification unit.. The purpose of this cluster-randomized effectiveness study was to measure the effects of single-session group lyric analysis interventions on withdrawal and craving with patients on a detoxification unit. A secondary purpose of this study was to determine if relationships existed between treatment effects and participants' familiarity with the song.. Participants (N = 144) were cluster-randomized to experimental (posttest only) or wait-list control (pretest only) conditions to provide treatment to all participants in an inclusive single-session design.. Although participants in the experimental condition had lower withdrawal and craving means than participants in the control condition, these differences were not significant. Familiarity of the song in the lyric analysis was not related to withdrawal or craving.. Group-based lyric analysis interventions may be effective for temporarily relieving withdrawal and craving in patients on a detoxification unit. Familiarity of the song did not affect results. Implications for clinical practice, suggestions for future research, and limitations are provided.

Topics: Adult; Alcoholism; Central Nervous System Depressants; Cocaine; Cocaine-Related Disorders; Craving; Dopamine Uptake Inhibitors; Ethanol; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Music Therapy; Narcotics; Psychotherapy, Group; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Young Adult

Diacetylmorphine hydrochloride (the active ingredient in heroin), delivered under supervision, is effective for the treatment of severe opioid use disorder. However, owing to political and regulatory barriers, it is not available in many settings around the world, which limits the options for many long-term street opioid injectors not attracted into or retained in available treatments.. To test if injectable hydromorphone hydrochloride is noninferior to injectable diacetylmorphine in reducing illicit heroin use for chronic injection opioid users after 6 months of intervention.. The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) was a phase 3, double-blind, noninferiority trial. The study randomized 202 long-term street opioid injectors in Vancouver, British Columbia, Canada. Eligible participants were recruited between December 19, 2011, and December 18, 2013. Both intent-to-treat (ITT) and per-protocol (PP) analyses were conducted.. Participants were randomly assigned to receive injectable diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under supervision.. Primary and coprimary efficacy outcomes were self-reported days of street heroin use (primary), days of any street-acquired opioids in the prior 30 days (noninferiority margin, 4 days), and the proportion of urinalyses positive for street heroin markers (margin, 10% of the observed rate in the diacetylmorphine group). The mean differences between diacetylmorphine and hydromorphone for the ITT and PP analyses were reported.. The study included 202 participants; 100 randomized to receive hydromorphone and 102 to diacetylmorphine. Their mean (SD) age was 44.33 (9.63) years, and 30.7% (62 of 202) were women. Noninferiority of hydromorphone was confirmed in the PP analysis (-1.44; 90% CI, -3.22 to 0.27) for street heroin use, although the margin of 4 days was not excluded in the ITT analysis (-2.34; 90% CI, -4.14 to -0.52). Noninferiority was confirmed for any street opioids in the ITT analysis (-0.85; 90% CI, -2.97 to 1.25) and the PP analysis (-0.15; 90% CI, -2.09 to 1.76), as well as for the urinalyses (0.09; 90% CI, -0.02 to 0.19 for the ITT analysis and 0.13; 90% CI, 0.02-0.24 for the PP analysis). There were 29 SAEs considered to have some relationship with the injection medication, 5 in the hydromorphone group and 24 in the diacetylmorphine group (rate ratio, 0.21; 95% CI, 0.06-0.69). Seizures and overdoses accounted for 25 of the 29 related SAEs.. This study provides evidence to suggest noninferiority of injectable hydromorphone relative to diacetylmorphine for long-term opioid dependence. In jurisdictions where diacetylmorphine is currently not available or for patients in whom it is contraindicated or unsuccessful, hydromorphone could be offered as an alternative.. clinicaltrials.gov Identifier: NCT01447212.

Topics: Adult; British Columbia; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Hydromorphone; Illicit Drugs; Injections, Intravenous; Intention to Treat Analysis; Long-Term Care; Male; Middle Aged; Needle-Exchange Programs; Substance Abuse Detection

To determine the efficacy of contingency management (CM), targeting cocaine use, as an add-on intervention for heroin dependent patients in supervised heroin-assisted treatment (HAT) with frequent cocaine use.. Multi-center, open-label, parallel group, randomized controlled trial.. Twelve specialized addiction treatment centers for HAT in The Netherlands; April 2006-January 2011.. 214 chronic, treatment-refractory heroin dependent patients in HAT, with frequent cocaine use.. Routine, daily supervised diacetylmorphine treatment, co-prescribed with oral methadone (HAT), with and without 6 months contingency management for cocaine use as an add-on intervention; HAT+CM and HAT-only, respectively.. Primary outcome was the longest, uninterrupted duration of cocaine abstinence, based upon laboratory urinalysis. Secondary outcome measures included other cocaine-related measures, treatment retention in HAT, and multi-domain health-related treatment response.. In an intention-to-treat analysis, HAT+CM was more effective than HAT-only in promoting longer, uninterrupted duration of cocaine abstinence (3.7 weeks versus 1.6 weeks; negative binomial regression: Exp(B)=2.34, 95%-CI: 1.70-3.23; p<0.001). This result remained significant in sensitivity analyses and was supported by all secondary, cocaine-related outcome measures. Treatment retention in HAT was high (91.6%) with no difference between the groups. The improvement in multi-domain health-related treatment response during the trial was numerically higher in HAT+CM (from 37.4% to 53.1%; +15.7%) than in HAT-only (from 44.5% to 46.5%; +2.0%), but this difference was statistically not significant.. Contingency management is an effective add-on intervention to promote longer, uninterrupted periods of cocaine abstinence in chronic, treatment-refractory heroin dependent patients in heroin-assisted treatment with frequent cocaine use. The trial has been registered in The Netherlands National Trial Register under clinical trial registration number NTR4728.

Topics: Adult; Analgesics, Opioid; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Netherlands; Time Factors; Treatment Outcome

In 2013, during a recent heroin-assisted treatment trial, participants in heroin-assisted treatment (HAT) decreased significantly more their street heroin use than participants in oral methadone treatment. After the trial, HAT was discontinued. To examine whether the treatment benefits were sustained three months after the trial, the use of street heroin by the participants was analyzed in a follow-up study.. At the follow-up assessment, street heroin use increased in the experimental group. The two groups no longer showed a significant difference (p=0.55) in the level of street heroin use.. A predetermined and forced end of HAT was followed by a significant increase in the level of street level use.

Topics: Follow-Up Studies; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Time Factors

The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.

Topics: Adult; Brain Diseases; Craving; Cues; Female; Gray Matter; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Narcotics; Neuropsychological Tests; Organ Size; Prefrontal Cortex

The Randomized Injectable Opioid Treatment Trial (RIOTT) compared supervised injectable heroin (SIH) and supervised injectable methadone (SIM) with optimized oral methadone (OOM) (ISRCTN0133807). Heroin addicts (previously unresponsive to treatment) made significant reductions in street heroin use at 6 months when treated with SIH. We now examine secondary outcomes.. Multi-site randomized controlled trial (RCT) comparing SIH versus OOM and SIM versus OOM.. Three supervised injectable opiate clinics in England.. Chronic refractory heroin addicts continuing to inject street heroin virtually daily despite oral substitution treatment (n = 127), randomized to either SIH(n = 43), SIM(n = 42) or OOM(n = 42). All received high levels of medical and psychosocial support.. wider drug use, crime, health and social functioning at 6 months.. At 6 months, no significant differences were found between treatment groups in wider drug use (crack/cocaine, benzodiazepines, alcohol), physical and mental health (SF-36) or social functioning. Within each treatment group, significant reductions were observed in crime [SIH = odds ratio (OR) 0.05; P < 0.001; SIM = OR 0.11; P = 0.002; OOM = OR 0.11; P = 0.003] and money spent per week on illicit drugs (SIH = mean change £-289.43; P < 0.001; SIM = mean change £-183.41; P < 0.001; OOM = mean change £-162.80; P < 0.001), with SIH significantly more likely to have reduced money spent on illicit drugs versus OOM (mean difference £-92.04; P < 0.001). Significant improvements were seen in physical health for SIH and SIM (SIH = mean change 3.97; P = 0.008; SIM = mean change 4.73; P = 0.002) and mental health for OOM (mean change 6.04; P = 0.013).. Supervised injectable heroin treatment and supervised injectable methadone treatment showed no clearly identified benefit over optimized oral methadone in terms of wider drug use, crime, physical and mental health within a 6-month period, despite reducing street heroin use to a greater extent. However, all interventions were associated with improvements in these outcomes.

Topics: Administration, Oral; Adult; Alcohol Drinking; Analgesics, Opioid; Cocaine-Related Disorders; Comorbidity; Crime; Employment; England; Female; Health Status; Heroin; Heroin Dependence; Housing; Humans; Illicit Drugs; Injections, Intravenous; Interpersonal Relations; Linear Models; Male; Methadone; Needle-Exchange Programs; Opiate Substitution Treatment; Substance Abuse, Intravenous; Treatment Outcome

Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction.

Topics: Adrenocorticotropic Hormone; Adult; Amygdala; Analgesics, Opioid; Bayes Theorem; Brain; Double-Blind Method; Fear; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Models, Neurological; Stress, Psychological; Surveys and Questionnaires; Time Factors

To investigate baseline and concurrent predictors of non-use of illicit heroin among participants randomized to injectable opioids in the North American Opiate Medication Initiative (NAOMI) clinical trial.. NAOMI was an open-label randomized controlled trial comparing the effectiveness of injectable diacetylmorphine and hydromorphone for long-term opioid-dependency. Outcomes were assessed at baseline and during treatment (3, 6, 9, 12months). Days of non-use of illicit heroin in the prior month at each follow-up visit were divided into three categories: Non-use; Low use (1 to 7days) and High use (8days or more). Tested covariates were: Sociodemographics, Health, Treatment, Drug use and illegal activities. Mixed-effect proportional odds models with random intercept for longitudinal ordinal outcomes were used to assess the predictors of the non-use of illicit heroin.. 139 participants were included in the present analysis. At each follow-up visit, those with non-use of illicit heroin represented 47.5% to 54.0% of the sample. Fewer days of cocaine use (p=0.074), fewer days engaged in illegal activities at baseline (p<0.01) and at each visit (p<0.01), less money spent on drugs (p<0.001), days with injection opioid or oral methadone treatment (p<0.001) and total mg of injectable opioids taken (p<0.001), independently predicted lower use of illicit heroin.. The independent effect of several concurrent factors besides the injection of opioid dose suggests benefits from the clinic that go beyond the provision of the medication alone. Thus, this supervised model of care presents an opportunity to maximize the beneficial impact of medical and psychosocial components of the treatment on improving outcomes associated with non-use of illicit heroin.

Topics: Adult; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Hydromorphone; Injections; Male; Narcotics; Time; Treatment Outcome

Heroin-assisted treatment (HAT) can improve the condition of heroin addicts still using street heroin after a methadone treatment. In Belgium, a new trial compared the efficacy of a HAT to existing methadone maintenance treatment.. In this randomised controlled trial, HAT was limited to 12 months. Participants were assessed every 3 months. They were responders if they showed improvement on the level of street heroin use, health or criminal involvement.. 74 participants were randomised in the trial. The experimental group (n = 36) counted 30% of responders more than the control group (n = 38) at each assessment point (p < 0.05), except at 12 months where the difference (11%) was no longer significant (p = 0.35). Still, after 12 months, participants in the experimental group reported significantly greater improvements (p < 0.05) than the control group on the level of street heroin use and on the level of physical and mental health. Both groups reported significantly less criminal acts after 12 months (p < 0.001), but with no significant difference between the groups.. This trial confirms the short-term efficacy of HAT for severe heroin addicts, who already failed methadone treatment.

Topics: Adult; Belgium; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Opiate Substitution Treatment; Treatment Outcome

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction.

Topics: Adult; Cerebral Cortex; Cross-Over Studies; Double-Blind Method; Echo-Planar Imaging; Female; Functional Laterality; Heroin; Heroin Dependence; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Narcotics; Neural Pathways; Outpatients; Oxygen; Psychiatric Status Rating Scales; Statistics as Topic; Thalamus; Young Adult

To evaluate a heroin overdose management training programme for family members based on emergency recovery procedures and take-home naloxone (THN) administration.. A two-group, parallel-arm, non-blinded, randomized controlled trial of group-based training versus an information-only control.. Training events delivered in community addiction treatment services in three locations in England.. A total of 187 family members and carers allocated to receive either THN training or basic information on opioid overdose management (n = 95 and n = 92, respectively), with 123 participants completing the study.. The primary outcome measure was a self-completion Opioid Overdose Knowledge Scale (OOKS; range 0-45) and an Opioid Overdose Attitudes Scale (OOAS; range 28-140) was the secondary outcome measure. Each group was assessed before receiving their assigned condition and followed-up 3 months after. Events of witnessing and managing an overdose during follow-up were also recorded.. At follow-up, study participants who had received THN training reported greater overdose-related knowledge relative to those receiving basic information only [OOKS mean difference, 4.08 (95% confidence interval, 2.10-6.06; P < 0.001); Cohen's d = 0.74 (0.37-1.10)]. There were also more positive opioid overdose-related attitudes among the trained group at follow-up [OOAS mean difference, 7.47 (3.13-11.82); P = 0.001; d = 0.61 (0.25-0.97)]. At the individual level 35 and 54%, respectively, of the experimental group increased their knowledge and attitudes compared with 11 and 30% of the control group. During follow-up, 13 participants witnessed an overdose with naloxone administered on eight occasions: five among the THN-trained group and three among the controls.. Take-home naloxone training for family members of heroin users increases opioid overdose-related knowledge and competence and these benefits are well retained after 3 months.

Topics: Adult; Caregivers; Drug Overdose; England; Family; Female; Health Education; Health Knowledge, Attitudes, Practice; Heroin; Heroin Dependence; Home Nursing; Humans; Male; Naloxone; Narcotic Antagonists

Negative emotional states and abnormal stress reactivity are central components in drug addiction. The brain stress system in the amygdala is thought to play a key role in the maintenance of drug dependence through negative reinforcement. Although acute heroin administration was found to reduce anxiety, craving, and stress hormone release, whether these effects are reflected in amygdala activity has not yet been investigated.. With a randomized, crossover, double-blind design, saline and heroin were administered to 22 heroin-dependent patients, whereas 17 healthy control subjects were included for the placebo administration only. We used functional magnetic resonance imaging to investigate blood oxygen level-dependent responses during fearful faces processing. Stress reactivity was measured by adrenocorticotropic hormone levels and by cortisol concentrations in serum and saliva 60 min after substance administration. Anxiety and craving levels were assessed with self-report ratings.. Heroin administration acutely reduced the left amygdala response to fearful faces relative to the saline injection. Patients receiving saline showed a significantly higher left amygdala response to fearful faces than healthy control subjects, whose activity did not differ from patients receiving heroin. The left amygdala activity correlated significantly with scores on state-anxiety and levels of adrenocorticotropic hormone, serum cortisol, and saliva cortisol among all patients and control subjects.. Our results show a direct relation between the acute heroin effects on stress-related emotions, stress reactivity, and left amygdala response to negative facial expressions. These findings provide new insights into the mechanisms underlying negative reinforcement in heroin addiction and the effects of regular heroin substitution.

Topics: Adrenocorticotropic Hormone; Adult; Amygdala; Anxiety; Brain Mapping; Cerebrovascular Circulation; Cross-Over Studies; Double-Blind Method; Facial Expression; Fear; Female; Functional Laterality; Heroin; Heroin Dependence; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Narcotics; Oxygen; Pattern Recognition, Visual; Stress, Psychological

Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.

Topics: Adult; Analgesics, Opioid; Bayes Theorem; Cognition; Cross-Sectional Studies; Double-Blind Method; Female; Heroin; Heroin Dependence; Humans; Image Processing, Computer-Assisted; Inhibition, Psychological; Magnetic Resonance Imaging; Male; Middle Aged; Models, Neurological; Neural Pathways; Neuropsychological Tests; Oxygen; Prefrontal Cortex

Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients. Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01). Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.

Topics: Adrenocorticotropic Hormone; Adult; Case-Control Studies; Chromatography, High Pressure Liquid; Cross-Over Studies; Double-Blind Method; Female; Heroin; Heroin Dependence; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Substance Abuse, Intravenous; Young Adult

Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No-Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition.

Topics: Adult; Attention; Cognition; Cross-Over Studies; Double-Blind Method; Female; Frontal Lobe; Functional Neuroimaging; Heroin; Heroin Dependence; Humans; Inhibition, Psychological; Male

Despite evidence of the effectiveness of injectable opioid treatment compared with oral methadone for chronic heroin addiction, the additional cost of injectable treatment is considerable, and cost-effectiveness uncertain.. To compare the cost-effectiveness of supervised injectable heroin and injectable methadone with optimised oral methadone for chronic refractory heroin addiction.. Multisite, open-label, randomised controlled trial. Outcomes were assessed in terms of quality-adjusted life-years (QALYs). Economic perspective included health, social services and criminal justice resources.. Intervention costs over 26 weeks were significantly higher for injectable heroin (mean £8995 v. £4674 injectable methadone and £2596 oral methadone; P<0.0001). Costs overall were highest for oral methadone (mean £15 805 v. £13 410 injectable methadone and £10 945 injectable heroin; P = n.s.) due to higher costs of criminal activity. In cost-effectiveness analysis, oral methadone was dominated by injectable heroin and injectable methadone (more expensive and less effective). At willingness to pay of £30 000 per QALY, there is a higher probability of injectable methadone being more cost-effective (80%) than injectable heroin.. Injectable opioid treatments are more cost-effective than optimised oral methadone for chronic refractory heroin addiction. The choice between supervised injectable heroin and injectable methadone is less clear. There is currently evidence to suggest superior effectiveness of injectable heroin but at a cost that policy makers may find unacceptable. Future research should consider the use of decision analytic techniques to model expected costs and benefits of the treatments over the longer term.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Chronic Disease; Cost Savings; Cost-Benefit Analysis; Crime; Health Care Costs; Heroin; Heroin Dependence; Humans; Injections; Intention to Treat Analysis; Methadone; Middle Aged; Opiate Substitution Treatment; Outcome Assessment, Health Care; Patient Compliance; Quality-Adjusted Life Years; United Kingdom; Young Adult

Heroin dependence is a chronic relapsing brain disorder, characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria, relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study, we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin-assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross-over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method, we used a pulsed arterial spin labeling (ASL) sequence based on a flow-sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8), using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo, heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self- and emotional regulation effects of heroin in maintenance treatment.

Topics: Adult; Cerebral Arteries; Cross-Over Studies; Female; Gyrus Cinguli; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Narcotics; Prefrontal Cortex; Regional Blood Flow; Single-Blind Method

The study investigates patients' pre-treatment expectations of, and post-treatment satisfaction with, supervised injectable opiate treatment delivered within UK's first such clinics within the Randomised Injectable Opiate Treatment Trial (RIOTT) (ISRCTN0133807).. Data were collected from 127 chronic heroin addicts recruited to RIOTT and randomised to receive supervised injectable (heroin or methadone) treatment or optimised oral maintenance treatment at supervised injectable maintenance clinics in London, Darlington and Brighton.. Of 127 RIOTT patients, 113 (89%) provided responses to structured enquiry about treatment expectations, and 94 (74%) subsequent responses about treatment satisfaction (at six months). Patients were hoping that injectable heroin treatment would: reduce substance misuse (81%); help achieve normality, routine and structure (16%); and increase education and work prospects (15%). At six months, an area of treatment satisfaction most commonly reported by all three trial groups was reduced substance misuse (supervised injectable heroin 59%, supervised injectable methadone 56%, optimised oral methadone 54%). Most found supervision acceptable, but some desired modifications were also identified.. Patients previously considered non-responsive to treatment appear to have similar treatment expectations and aspirations as other drug users in treatment. Supervised injectable opioid treatment patients consistently reported treatment satisfaction but also that more could be done to optimise aspects of current arrangement. This raised the challenging issue of the extent to which opinions of patients need to be taken into consideration in shaping future treatment provision. Future research may need to examine the extent of expectations 'fit' and the relationship between treatment sought and received.

Topics: Administration, Oral; Adult; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Injections; Male; Methadone; Middle Aged; Needle-Exchange Programs; Patient Satisfaction; Treatment Outcome; United Kingdom

Studies from several countries have by now shown the effectiveness of heroin-assisted treatment in comparison to methadone treatment. However, only few long-term results exist, and in particular data with a focus on social integration of the patients are scarce.. The study analyzes the course of long-term social integration among the patients of the German diamorphine study.. Individual changes in health, drug use and social integration among patients who had participated in a 4-year diamorphine treatment (n=156) were described and statistically tested by means of repeated measures analyses. The criteria used are based on the instruments OTI-HSS and SCL-90-R, on medical findings, urinalyses, and on variables as well as composite scores from the European Addiction Severity Index.. In all domains significant improvements were found after long-term treatment. The percentage of patients employed or currently working had increased 3-fold up to 40% after 4 years. Moreover, the living situation and leisure behaviour improved, and criminal activities declined markedly. The main influencing factor for successful social integration after 4 years of treatment is the ability to work.. Heroin-assisted treatment is a long-term effective treatment for severely dependent opiate addicts with respect to stabilization of health, reduction of illegal drug use and improvement of social integration. Furthermore, the results show that processes of social (re-)integration of drug users take time.

Topics: Activities of Daily Living; Adult; Crime; Drug Substitution; Employment; Female; Germany; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Recovery of Function; Risk Factors; Socioeconomic Factors; Treatment Outcome

Cocaine dependence has proved difficult to treat, whether it occurs alone or in combination with opiate dependence. No intervention has been demonstrated to be uniquely effective. Patients might benefit most from combined pharmacotherapeutic and psychotherapeutic interventions. The present study sought to evaluate the feasibility, tolerability, and efficacy of methylphenidate (MP) and cognitive-behavioral group therapy (CBGT) for cocaine dependence in diacetylmorphine-maintained patients. Sixty-two cocaine-dependent diacetylmorphine-maintained patients participated in a dual-site, double-blind, placebo-controlled pilot trial with 4 treatment conditions. The participants were randomly assigned to receive MP or a placebo each combined with either CBGT or treatment as usual for 12 weeks. Methylphenidate 30 mg and a placebo in identical capsules were administered onsite twice daily under supervision in a fixed-dose regimen without titration. Manual-guided CBGT consisted of 12 weekly sessions. Participation in the CBGT sessions was voluntary. Primary outcome measures were retention in pharmacologic treatment, cocaine-free urine samples, self-reported cocaine use, and adverse effects. Urine screens were performed thrice weekly. Seventy-one percent of the participants completed the study protocol. Methylphenidate was well tolerated with similar retention rates compared with the placebo. No serious adverse effects occurred. No difference in cocaine-free urine screens was found across the 4 treatment groups. Self-reported cocaine use was reduced in all 4 study groups. Methylphenidate and CBGT did not provide an advantage over a placebo or treatment as usual in reducing cocaine use. There were no signs of additive benefits of MP and CBGT. Because of the small sample size, the results are preliminary.

Topics: Adult; Analgesics, Opioid; Central Nervous System Stimulants; Chi-Square Distribution; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Feasibility Studies; Female; Heroin; Heroin Dependence; Humans; Kaplan-Meier Estimate; Male; Methylphenidate; Opiate Substitution Treatment; Pilot Projects; Substance Abuse Detection; Switzerland; Time Factors; Treatment Outcome; Urinalysis

To investigate in heroin-assisted treatment (HAT) compared to methadone maintenance treatment (MMT): the course of heroin craving and illicit heroin use, their mutual association, and their association with multi-domain treatment response.. RCTs on the efficacy of 12 months co-prescribed injectable or inhalable HAT compared to 12 months continued oral MMT.. Outpatient treatment in MMT- or specialized HAT-centers in the Netherlands.. Chronic, treatment-refractory heroin dependent patients (n=73). STUDY PARAMETERS: General craving for heroin (Obsessive Compulsive Drug Use Scale); self-reported illicit heroin use; multi-domain treatment response in physical, mental and social health and illicit drug use.. The course of heroin craving and illicit heroin use differed significantly, with strong reductions in HAT but not in MMT. General heroin craving was significantly related to illicit heroin use. Heroin craving was not and illicit heroin use was marginally related to multi-domain treatment response, but only in MMT and not in HAT.. Heroin craving and illicit heroin use were significantly associated and both strongly decreased in HAT but not in MMT. Craving was not related to multi-domain treatment response and illicit heroin use was marginally related to treatment response in MMT, but not in HAT. The latter was probably due to the strong reduction in illicit heroin use in most patients in HAT and the small sample size of the sub-study. It is hypothesized that the strong reductions in craving for heroin in HAT are related to the stable availability of prescribed, pharmaceutical grade heroin.

Topics: Adult; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Narcotics; Opiate Substitution Treatment; Patient Compliance; Time Factors; Treatment Outcome

Positron emission tomography (PET) imaging studies have shown that addiction to a number of substances of abuse is associated with a decrease in dopamine D(2/3) receptor binding and decreased presynaptic dopamine release in the striatum. Some studies have also shown that these reductions are associated with the severity of addiction. For example, in cocaine dependence, low dopamine release is associated with the choice to self-administer cocaine. The goal of the present study was to investigate these parameters of striatal dopamine transmission in heroin dependence and their association with drug seeking behavior.. Heroin-dependent and healthy control subjects were scanned with [(11)C]raclopride before and after stimulant administration (methylphenidate) to measure striatal D(2/3) receptor binding and presynaptic dopamine release. After the PET scans, the heroin-dependent subjects performed heroin self-administration sessions.. Both striatal D(2/3) receptor binding and dopamine release were reduced in the heroin-dependent subjects compared with healthy control subjects. However, neither PET measure of dopamine transmission predicted the choice to self-administer heroin.. These findings show that heroin addiction, like addiction to other drugs of abuse, is associated with low D(2/3) receptor binding and low presynaptic dopamine. However, neither of these outcome measures was associated with the choice to self-administer heroin.

Topics: Adult; Behavior, Addictive; Choice Behavior; Corpus Striatum; Dopamine; Female; Heroin; Heroin Dependence; Humans; Male; Methylphenidate; Neuroimaging; Positron-Emission Tomography; Presynaptic Terminals; Raclopride; Radioligand Assay; Receptors, Dopamine D2; Self Administration

Heroin dependence is a chronic relapsing disorder characterized by the compulsion to seek and use heroin. Stress and craving are seen as key factors for heroin use. Moreover, altered hypothalamic-pituitary-adrenal (HPA) axis function has been frequently reported. However, the acute effects of diacetylmorphine (DAM) on HPA axis activity and craving have not been investigated in a controlled study. The present randomized controlled study examined whether DAM administration differs from placebo (saline) administration with regard to HPA axis response and heroin craving.. In a crossover experiment, 28 DAM-maintained heroin-dependent patients were first injected with DAM and then saline, or the converse. Plasma adrenocorticotropic hormone (ACTH) and cortisol in saliva and serum were measured at baseline and 20 and 60 min after both injections. Heroin craving was measured at baseline and 60 min after both injections, by means of the Heroin Craving Questionnaire.. Compared to saline, DAM administration induced a significant decrease in plasma ACTH (p < 0.01), serum cortisol (p < 0.0001) and saliva cortisol (p < 0.01), as well as in craving (p < 0.0001), over time.. Since acute DAM administration suppresses the stress response, DAM-assisted treatment may be an effective alternative to methadone maintenance in stress-sensitive heroin-dependent patients.

Topics: Adult; Behavior, Addictive; Cross-Over Studies; Female; Heroin; Heroin Dependence; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Single-Blind Method; Young Adult

The aim of this study was to evaluate the feasibility of conducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the capacity of oral DAM to block opiate withdrawal and clinicians' ability to distinguish it from morphine and methadone. This was a randomized, phase II, double-blind, multicenter pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone administered twice a day during 10 days. Forty-five heroin-dependent patients were randomly assigned to these three treatment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immediate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments.

Topics: Administration, Oral; Adult; Behavior, Addictive; Delayed-Action Preparations; Double-Blind Method; Feasibility Studies; Female; Heroin; Heroin Dependence; Humans; Inpatients; Male; Methadone; Morphine; Opiate Substitution Treatment; Physicians; Pilot Projects; Psychiatric Status Rating Scales

Heroin dependence (HD) is a chronic relapsing brain disorder characterized by a compulsion to seek and use heroin. Stress is seen as a key factor for heroin use. Methadone maintenance and the prescription of pharmaceutical heroin [diacetylmorphine (DAM)] are established treatments for HD in several countries. The present study examined whether DAM-maintained patients and methadone-maintained patients differ from healthy controls in startle reflex and cortisol levels. Fifty-seven participants, 19 of each group matched for age, sex and smoking status, completed a startle session which included the presentation of 24 bursts of white noise while eye-blink responses to startling noises were recorded. Salivary cortisol was collected three times after awakening, before, during and after the startle session. DAM was administered before the experiment, while methadone was administered afterwards. Both heroin-dependent patient groups exhibited significantly smaller startle responses than healthy controls (P < 0.05). Whereas the cortisol levels after awakening did not differ across the three groups, the experimental cortisol levels were significantly lower in DAM-maintained patients, who received their opioid before the experiment, than in methadone-maintained patients and healthy controls (P < 0.0001). Opioid maintenance treatment for HD is associated with reduced startle responses. Acute DAM administration may suppress cortisol levels, and DAM maintenance treatment may represent an effective alternative to methadone in stress-sensitive, heroin-dependent patients.

Topics: Administration, Oral; Adult; Arousal; Depression, Chemical; Female; Heroin; Heroin Dependence; Humans; Hydrocortisone; Infusions, Intravenous; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Reflex, Startle; Secondary Prevention; Stress, Psychological

Opioid detoxification is not an effective stand-alone treatment for heroin dependence but is nevertheless an essential step in the path to recovery. There has been relatively little previous controlled research on the impact of treatment setting on the likelihood of successful completion of detoxification. In this study, 68 opioid-dependent patients receiving community treatment (predominantly with methadone) and requesting detoxification were randomly assigned to an inpatient versus outpatient setting. Both groups received the same medication (lofexidine), and the primary outcome measure was being opioid-free at detoxification completion. More inpatients (n = 18, 51.4%) than outpatients (n = 12, 36.4%) completed detoxification, but this difference was not statistically significant (χ(2) = 1.56, p = .21). However, the outpatient group received a significantly longer period of medication, and when the length of detoxification was controlled for, the results favored the inpatient setting (Exp(B) = 13.9, 95% confidence interval = 2.6-75.5, p = .002). Only 11 (16%) participants were opioid-free at the 1-month follow-up and 8 at the 6-month follow-up, with no between-group difference. Inpatient and outpatient opioid detoxification settings were not significantly different in completion or follow-up abstinence rates, but aspects of the study design may have favored the outpatient setting. Future studies should test patient characteristics that predict better outcomes in each setting.

Topics: Analgesics, Opioid; Clonidine; Female; Heroin; Heroin Dependence; Humans; Inpatients; Male; Methadone; Narcotics; Opioid-Related Disorders; Outcome Assessment, Health Care; Outpatients; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours.

Topics: Analgesics, Opioid; Comorbidity; Crime; Drug Administration Schedule; Female; Heroin; Heroin Dependence; Humans; Interview, Psychological; Male; Mental Disorders; Methadone; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Self Report; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome; Violence

Several international clinical studies have found diamorphine treatment for opioid-dependent patients to show significantly better effects compared with methadone maintenance treatment.. This analysis of the German trial of heroin-assisted treatment investigates the effects on patients' health and drug use after switching from 12-month methadone to 12-month diamorphine treatment under similar study conditions.. For a period of 24 months, the state of health was explored using the Opiate Treatment Index (OTI) health scale and the Symptom Checklist-90-R (SCL-90-R), while drug use and social situation by an extended version of the European Addiction Severity Index (EuropASI) every 6 months. Changes in these criteria were tested for significance by repeated measures analyses. Of the 434 patients, who started the 2nd year of study treatment, 90 were methadone-diamorphine switchers, and 344 received diamorphine for 2 years.. In the 2nd year, the methadone-diamorphine switchers succeed in catching up with the diamorphine patients. After switching to diamorphine, significant improvements in health and use of street heroin and cocaine were achieved during 1 year of diamorphine treatment.. The results of the course of methadone-diamorphine switchers are a methodologically independent contribution toward confirming the positive effects of diamorphine treatment for difficult-to-treat opioid-dependent patients. This study supports the hypothesis that changing from optimized methadone treatment under the conditions of the clinical trial to diamorphine treatment is associated with improvements in health and drug use behavior. The study's limitations are noted.

Topics: Adult; Analgesics, Opioid; Drug Substitution; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Treatment Outcome

In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study.. During pregnancy, some women were exposed to illicit agents: cannabis (42% in the buprenorphine group vs. 58% in the methadone-treated group), heroin (17% vs. 44%), or cocaine (3% vs. 11%). Pregnancies ended in 85 vs. 40 live births, one vs. two stillbirths, two vs. one spontaneous abortion, two vs. one voluntary termination, and one vs. one medical termination in the buprenorphine and the methadone groups, respectively. Newborns had a birth weight of 2,892 ± 506 g (buprenorphine) vs. 2,731 ± 634 g (methadone) and a body length of 47.6 ± 2.5 cm vs. 47.1 ± 3 cm. 18.8% vs. 10% of newborns were delivered before 37 weeks of amenorrhea. Neonatal withdrawal syndrome occurred more frequently in the methadone group (62.5% vs. 41.2, p = 0.03). After adjustment for heroin exposure in late pregnancy, rates of neonatal withdrawal were no longer different between the methadone and buprenorphine groups. Twenty-one babies (84%) in the methadone group and 20 (57%) in the buprenorphine group (p = 0.03) required opiate treatment.. We did not observe more frequent malformations or cases of withdrawal syndrome in the buprenorphine group than in the methadone-treated group. Buprenorphine appears to be as safe as the currently approved substitute methadone considered to date as the reference treatment for pregnant opioid-dependent women.

Topics: Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies

1. Tetrodotoxin (TTX) is a powerful sodium channel blocker extracted from the puffer fish. The efficacy and safety of TTX as monotherapy for the treatment of acute heroin withdrawal syndrome were evaluated in the present study. This 7-day, multicentre, randomized, double-blind, placebo-controlled study was carried out between December 2008 and October 2009. In total, 216 patients who met the Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of heroin addiction were recruited. After providing written informed consent, subjects were randomly assigned to double-blind treatment in one of the following groups: 5 μg TTX group (group 1), 10 μg TTX group (group 2) or the placebo group (group 3). 2. Evidence suggests that both 5 and 10 μg TTX significantly reduced withdrawal symptoms by day 3 compared with placebo, and there was no significant difference in the incidence of adverse events in the three groups. 3. In conclusion, this clinical trial shows that TTX (5 and 10 μg given t.i.d.) is effective in alleviating opiate withdrawal symptoms with few side-effects.

Topics: Adult; Behavior, Addictive; Cues; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Sodium Channel Blockers; Substance Withdrawal Syndrome; Tetrodotoxin; Treatment Outcome; Young Adult

To observe heroin cue-induced changes of cerebral functional magnetic resonance images (fMRI) and the effect of acupuncture of Zusanli (ST 36) on them under craving state in heroin-addicted volunteers.. Fourteen male volunteer heroin addicts were recruited in the present study. Brain images were acquired before, during (2 min) and after visualizing heroin (placed in a transparent glass mug) and acupuncture of Zusanli (ST 36) on a 1.5-T Siemens Symphony MRI system equipped with a standard head coil. Acupuncture stimulation was applied to bilateral Zusanli (ST 36) by manipulating a filiform needle at a frequency of about 60 cycles/min and an angle of about 180 degrees for 2 min. The acquired neuroimaging data were analyzed by AlphaSim, AFNI.. During heroin-visual stimulation, the markedly activated brain areas (increase of blood oxygen level-dependent signal) of fMRI were bilateral middle frontal gyrus, left cingulate gyrus, bilateral insula, occipital cortex, left cuneus, cerebellum, bilateral thalamus, right hippocampus and right amygdala etc. which are closely related to the human's craving psychological activities. When acupuncture given, meaning processing stronger sensory task, the heroin-addicted subjects showed apparent activation of the brain areas including the right anterior cingulate gyrus, right insula, thalamus, right hippocampal gyrus etc. which activation degrees were significant lower than those of heroin related visual stimulation.. Acupuncture of Zusanli (ST 36) can lessen heroin cue-induced activation degree of the brain areas involving psychological craving, suggesting that acupuncture is able to suppress the heroin addiction patients' drug abuse craving.

Topics: Acupuncture Therapy; Adult; Brain; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Radiography; Young Adult

Comorbid psychiatric disorders among opioid-dependent patients are associated with several negative outcome factors. However, outcomes of maintenance treatment have not been sufficiently established, and no evidence is available with respect to heroin-assisted treatment (HAT).. For patients in the German heroin trial outcome measures were analyzed for HAT versus methadone maintenance treatment (MMT) both for patients with and without a comorbid diagnosis according to CIDI.. 47.2% of the sample had at least one comorbid psychiatric diagnosis, mainly neurotic, stress-related or somatoform (F4) or affective (F3) disorders. HAT had a better outcome than MMT concerning improvement of health and reduction of illicit drug use in both comorbid and non-comorbid patients, but weaker effects were found in the comorbid group.. The better outcome of HAT also in comorbid patients suggests that psychiatric comorbidity should be an inclusion criterion for HAT. The weaker advantage of HAT may be due to pharmacological or methodological reasons.

Topics: Adult; Case Management; Combined Modality Therapy; Comorbidity; Diagnosis, Dual (Psychiatry); Female; Heroin; Heroin Dependence; Humans; Long-Term Care; Male; Mental Disorders; Methadone; Narcotics; Patient Education as Topic; Psychotherapy; Treatment Outcome

Severely opioid-dependent patients are at high risk of both acquiring and spreading the hepatitis C virus (HCV). It is uncertain, however, whether these patients are possible candidates for HCV treatment. We therefore explored treatment retention and adherence as well as sustained viral response in co-morbid severely opioid-dependent subjects under heroin maintenance, who previously failed in conventional substitution treatment or were not in any drug treatment.. All patients in heroin maintenance in the German heroin trial, who received standard antiviral HCV therapy with pegylated interferon and ribavirin, were included. Co-consumption of licit and illicit drugs was tolerated as long as it did not interfere with treatment.. Twenty-six patients in heroin maintenance were treated for chronic HCV infection. Both the Global Severity Index of the Symptom Checklist 90-R (average score 65.9) and the Opiate Treatment Index (average score 16.6) indicated relevant co-morbidity. Twenty-one patients (81%) were retained in treatment; the adherence rate was 92%. Eighteen patients (69%) achieved a sustained viral response, with a 100% response rate for genotype 2, 90% for genotype 3, and 42% for genotype 1.. This is the first study that investigates the feasibility of antiviral HCV treatment in a well-defined sample of co-morbid severely opioid-dependent subjects in heroin maintenance treatment. Viral response rates are comparable to non-drug-user populations. Within a need-adapted treatment setting, HCV treatment may even be extended to difficult-to-treat opioid-dependent patients.

Topics: Adult; Antiviral Agents; Female; Genotype; Germany; Health Status; Hepacivirus; Hepatitis C; Heroin; Heroin Dependence; Humans; Interferons; Male; Mental Health; Middle Aged; Narcotics; Ribavirin; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Viral Load; Young Adult

Using data from the North American Opioid Maintenance Initiative study, a Phase III randomized and parallel arm trial, this pilot study is aimed at testing if treatment response with injectable hydromorphone differs compared to diacetylmorphine in the treatment of long-term opioid addiction. A total of 140 long-term, treatment-refractory opioid-dependent individuals received either injectable diacetylmorphine (n = 115) or hydromorphone (n = 25), in a double-blind fashion, over 12 months. At the end of the study, none of the participants in the hydromorphone group thought they were definitely receiving this drug. Retention rates at 12 months with diacetylmorphine (87.8%; 95% confidence interval [CI] = 80.5%-92.7%) and hydromorphone (88.0%; 95% CI = 68.7%-96.1%) were virtually identical. The use of illicit heroin in the prior month declined from a mean of 26.6 and 26.3 days at baseline to 5.3 and 5.2 days at 12 month in the diacetylmorphine and hydromorphone groups, respectively. There were no differences between diacetylmorphine and hydromorphone in the adjusted mean scores of the European Addiction Severity Index. There were no differences in the safety profile of the medications. Hydromorphone may be similarly safe and effective as diacetylmorphine as opioid-agonist substitution treatment; future studies are required to confirm it. Further study will also be required to show that open-label hydromorphone can also successfully attract patients into care and retain them.

Topics: Adult; Double-Blind Method; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Hydromorphone; Injections; Methadone; Narcotics; Opioid-Related Disorders; Pilot Projects; Severity of Illness Index; Time Factors

Dropout and recidivism from addiction treatment has been found to be associated with individuals' readiness for change. Motivation for treatment among participants entering the North American Opiate Medication Initiative (NAOMI) randomized controlled trial, which compared heroin assisted treatment (HAT) to optimized methadone maintenance treatment (MMT), was assessed. Through multivariate regression, we aimed to determine whether baseline motivational status was predictive of four treatment outcomes: early dropout, 12-month retention, 12-month response to treatment, and time to discontinuation of treatment. Among the 251 out-of-treatment chronic opioid dependent patients recruited in Montreal, Quebec and Vancouver, British Columbia, 52% reported having a high level of motivation for treatment. HAT was statistically significantly more effective than MMT on each of the outcomes assessed. Baseline motivational status did not predict retention or time to discontinuation in either HAT or MMT. However, while patients were retained in HAT regardless of motivational status, motivated patients showed a more favourable response to treatment in terms of decreases in crime and illicit drug use. These results suggest that HAT successfully retains opioid dependent patients who otherwise may not have been attracted into existing treatment options, and may enhance the odds of successful rehabilitation among patients motivated for treatment.

Topics: Adult; British Columbia; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Motivation; Multivariate Analysis; Narcotics; Quebec; Regression Analysis; Treatment Outcome

Some heroin addicts persistently fail to benefit from conventional treatments. We aimed to compare the effectiveness of supervised injectable treatment with medicinal heroin (diamorphine or diacetylmorphine) or supervised injectable methadone versus optimised oral methadone for chronic heroin addiction.. In this multisite, open-label, randomised controlled trial, we enrolled chronic heroin addicts who were receiving conventional oral treatment (>or=6 months), but continued to inject street heroin regularly (>or=50% of days in preceding 3 months). Randomisation by minimisation was used to assign patients to receive supervised injectable methadone, supervised injectable heroin, or optimised oral methadone. Treatment was provided for 26 weeks in three supervised injecting clinics in England. Primary outcome was 50% or more of negative specimens for street heroin on weekly urinalysis during weeks 14-26. Primary analysis was by intention to treat; data were adjusted for centre, regular crack use at baseline, and treatment with optimised oral methadone at baseline. Percentages were calculated with Rubin's rules and were then used to estimate numbers of patients in the multiple imputed samples. This study is registered, ISRCTN01338071.. Of 301 patients screened, 127 were enrolled and randomly allocated to receive injectable methadone (n=42 patients), injectable heroin (n=43), or oral methadone (n=42); all patients were included in the primary analysis. At 26 weeks, 80% (n=101) patients remained in assigned treatment: 81% (n=34) on injectable methadone, 88% (n=38) on injectable heroin, and 69% (n=29) on oral methadone. Patients on injectable heroin were significantly more likely to have achieved the primary outcome (72% [n=31]) than were those on oral methadone (27% [n=11], OR 7.42, 95% CI 2.69-20.46, p<0.0001; adjusted: 66% [n=28] vs 19% [n=8], 8.17, 2.88-23.16, p<0.0001), with number needed to treat of 2.17 (95% CI 1.60-3.97). For injectable methadone (39% [n=16]; adjusted: 30% [n=14]) versus oral methadone, the difference was not significant (OR 1.74, 95% CI 0.66-4.60, p=0.264; adjusted: 1.79, 0.67-4.82, p=0.249). For injectable heroin versus injectable methadone, a significant difference was recorded (4.26, 1.63-11.14, p=0.003; adjusted: 4.57, 1.71-12.19, p=0.002), but the study was not powered for this comparison. Differences were evident within the first 6 weeks of treatment.. Treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimised oral methadone. UK Government proposals should be rolled out to support the positive response that can be achieved with heroin maintenance treatment for previously unresponsive chronic heroin addicts.. Community Fund (Big Lottery) Research section, through Action on Addiction.

Topics: Administration, Oral; Adolescent; Adult; Aged; England; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Injections; Male; Methadone; Middle Aged; Narcotics; Prescription Drugs; Young Adult

Benzodiazepine (BZD) use has been found to be associated with poorer psychosocial adjustment, higher levels of polydrug use and more risk-taking behaviors among opioid dependent patients. The aim of this paper is to analyze the correlation between BZD use, BZD prescription and treatment outcome among participants in the German trial on heroin-assisted treatment. 1015 patients who participated in the study comparing heroin-assisted and methadone maintenance treatment (HAT & MMT) for 12 months were included in the analysis. Analyses were carried out to assess the association of treatment outcome with baseline BZD use, with ongoing BZD use and with different patterns of BZD prescription. Baseline BZD use correlated with lower retention rates but not with poorer outcome. Ongoing BZD use correlated with poorer outcomes. Significantly better outcomes were found in the course of phobic anxiety symptomatology for those with regular prescription of BZD. The percentage of BZD positive urine tests decreased more in HAT than in MMT. Poorer outcome for benzodiazepine users may be mediated by a higher severity of addiction. Cautious prescribing of benzodiazepines may be beneficial due to the reduction of overall illicit use.

Topics: Anti-Anxiety Agents; Benzodiazepines; Drug Prescriptions; Female; Germany; Heroin; Heroin Dependence; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions; Psychiatric Status Rating Scales; Risk-Taking; Substance-Related Disorders; Treatment Outcome

There is increasing evidence that health-related quality of life (HRQOL) is associated with a successful treatment and better outcome in opioid addiction. The aim of the present study was the longitudinal investigation of HRQOL in patients with severe opioid dependence, who were randomly assigned to four groups of medical and psychosocial treatment: heroin (diacetylmorphine) versus methadone and case management (CM) versus psychoeducation (PSE) respectively.. HRQOL (MSQoL) and physical health (OTI) were investigated in 938 subjects, who participated in the German multi-centre study examining the effects of heroin-assisted treatment in patients with severe opioid dependence. Data for the present analysis were taken from baseline and 12-month follow up.. Under both forms of maintenance and psychosocial treatment HRQOL improved significantly during the observation period. HRQOL improvement under maintenance with heroin exceeded improvement under methadone, especially with regard to subjective physical health. HRQOL improvement was significantly associated with better expert-rated physical health. Further analyses showed significant better improvement of HRQOL in subjects treated with PSE compared with CM.. The advantage of heroin with regard to the improvement of HRQOL may be partially explained by a better improvement of physical health under maintenance with heroin compared with methadone, which highlights the importance of a comprehensive model of health care for patients with severe opioid dependence. Future studies need to investigate the benefits of PSE for patients in maintenance therapy.

Topics: Adult; Aged; Aged, 80 and over; Case Management; Counseling; Education; Female; Heroin; Heroin Dependence; Humans; Interview, Psychological; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Quality of Life; Young Adult

Alcohol has been suggested to be a risk factor for opioid-dependent patients in methadone maintenance treatment (MMT). Literature shows that MMT has limited effects on alcohol use. Nevertheless, a decrease in alcohol use was detected in the Swiss heroin-assisted treatment (HAT) study. In this article, we carry out an in-depth analysis of the German HAT trial with the aim of determining whether alcohol use was affected among patients undergoing HAT and MMT. Analysis was carried out using self-reported data on consumption units of alcohol used (CU), Addiction Severity Index composite scores (ASI CSs), and carbohydrate-deficient transferrin (CDT) measures. Results suggest significant reduction of CU and CDT in both groups, yet larger effects in the HAT group. ASI CS significantly decreased in the HAT but not in the MMT group. The greater benefit of HAT in reducing alcohol use may be due to the greater daily frequency of dispensing heroin coupled with a requirement of sobriety at each dosing occasion.

Topics: Adult; Alcohol Drinking; Germany; Heroin; Heroin Dependence; Humans; Male; Methadone; Transferrin; Treatment Outcome

Heroin addiction is a chronic relapsing disease, best treated with opioid-agonist substitution therapy such as methadone maintenance. However, a subset of the most severely affected individuals do not benefit sufficiently from this treatment. The North American Opiate Medication Initiative (NAOMI) is a randomized clinical trial (RCT) to evaluate the hypothesis that pharmaceutical-grade heroin, diacetylmorphine (DAM) is more effective in retaining patients and improving their outcomes than Methadone Maintenance Treatment (MMT) among those with chronic, refractory injection opioid dependence.. The study aimed at randomizing 253 participants to two intervention arms: (1) MMT alone or (2) injectable opioids (DAM or hydromorphone) plus adjunctive MMT if deemed appropriate. The planned study duration was 3 years, with a 1-year intake period, 1 year of treatment, and an additional year of follow-up. The NAOMI trial was initiated in March 2005 at two Canadian sites (Vancouver and Montreal). This was the first multicenter RCT in North America to compare the relative efficacy of these different therapeutic strategies. We discuss the rationale behind the NAOMI study design, as well as the scientific and political issues and methodological challenges arising from the conduct of a trial that involves the prescription of a controlled substance to individuals with dependence on that substance.. Restrictive entry criteria led to the exclusion of many otherwise eligible participants, slowing recruitment into the study. Inability to offer DAM treatment beyond 12 months led to artificial boundary effects in the trial.. Addiction treatment research navigates between science and politics, and evidence-based medicine is many times confronted by moral beliefs. Political considerations influence study design to a further degree than in RCTs treating less-stigmatized disorders with more-reputable medications.

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Endpoint Determination; Heroin; Heroin Dependence; Humans; Methadone; North America; Politics; Research Design; Treatment Outcome

The objective of this research was to evaluate data from a randomized clinical trial that tested injectable diacetylmorphine (DAM) and oral methadone (MMT) for substitution treatment, using a multi-domain dichotomous index, with a Bayesian approach.. Sixty two long-term, socially-excluded heroin injectors, not benefiting from available treatments were randomized to receive either DAM or MMT for 9 months in Granada, Spain. Completers were 44 and data at the end of the study period was obtained for 50. Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration, used in a previous trial. Data was analyzed with Bayesian methods, using information from a similar study conducted in The Netherlands to select a priori distributions. On adding the data from the present study to update the a priori information, the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations.. In the experimental group (n = 27), the rate of responders to treatment was 70.4% (95% CI 53.287.6), and in the control group (n = 23), it was 34.8% (95% CI 15.354.3). The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis. Almost the whole distribution of the rates difference (the one for diacetylmorphine minus methadone) was located to the right of the zero, indicating the superiority of the experimental treatment.. The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments.. Current Controlled Trials ISRCTN52023186.

Topics: Administration, Oral; Bayes Theorem; Heroin; Heroin Dependence; Humans; Injections; Methadone; Narcotics; Treatment Outcome

Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence.. In an open-label, phase 3, randomized, controlled trial in Canada, we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment. Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment) were randomly assigned to receive methadone (111 patients) or diacetylmorphine (115 patients). The primary outcomes, assessed at 12 months, were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index.. The primary outcomes were determined in 95.2% of the participants. On the basis of an intention-to-treat analysis, the rate of retention in addiction treatment in the diacetylmorphine group was 87.8%, as compared with 54.1% in the methadone group (rate ratio for retention, 1.62; 95% confidence interval [CI], 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diacetylmorphine group and 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). The most common serious adverse events associated with diacetylmorphine injections were overdoses (in 10 patients) and seizures (in 6 patients).. Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)

Topics: Administration, Oral; Adult; Cocaine-Related Disorders; Double-Blind Method; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Hydromorphone; Illicit Drugs; Injections; Male; Methadone; Substance Abuse Detection; Substance Abuse, Intravenous

In October 2008, the North American Opiate Medication Initiative (NAOMI) research team released the primary outcomes of a randomized controlled trial aimed at testing whether the provision of pharmaceutical-grade heroin under medical supervision benefits people suffering from chronic opiate addictions who have not benefitted from other treatments. The treatment phase was completed in June 2008. Retention and response rates were high, suggesting that heroin-assisted therapy is a safe and highly effective treatment for people with chronic heroin addiction.

Topics: Adult; Canada; Drug Prescriptions; Female; Heroin; Heroin Dependence; Humans; Male; North America

The aim of the study was to evaluate the effect of substitution therapy in heroin addicted pregnant women on the course of pregnancy, perinatal outcomes and course of the neonatal abstinence syndrome.. A five-year randomised prospective comparative study. The study was carried out in the period of 2002-2007. The group of patients included 147 i.v. heroin-addicted pregnant women. All of them were outpatients of our Perinatal Care Unit. Their daily dose of heroin was approximately lg. Later, 30 women were disqualified from the study for breaking the randomised criteria engagement. The substitution therapy in women who agreed to undergo it, started during the I. trimester of pregnancy. Finally, 47 heroin, 32 methadone and 38 buprenorphine addicted women were enrolled in the study. Birthweight of newborns was compared with the national birthweight tables. Severity and duration of neonatal abstinence syndrome (NAS) were evaluated by Finnegan s score scale.. None of the women delivered before the end of 34th gestational week. We did not encounter any perinatal death or developmental defect. The lowest birthweight, the highest number of newborns with IUGR and the most numerous placental changes were found in the group of heroin-addicted women. The differences compared to the two groups receiving substitution therapy were statistically significant (p < 0.05). The severity and course of NAS were the most severe (p < 0.001) in newborns of women from the methadone group.. Comparison of the groups of outpatients is in many ways questionable because of the restricted possibility of the patients' control. The lifestyle of addicted women has the same impact as the drug use alone. This is probably the main reason for differences in some of the monitored parameters between individual groups. Based on our results we can state that substitution therapy provides pregnant women with the possibility of social stabilization and adequate prenatal care. substitution therapy decreases the street heroin consumption. Methadone notably protracts the newborn's abstinence syndrome. With regard to this fact, attention has been recently focused on substitution with buprenorphine that seems to be from this viewpoint a more considerate option.

Topics: Adult; Birth Weight; Buprenorphine; Female; Fetal Growth Retardation; Heroin; Heroin Dependence; Humans; Infant, Newborn; Life Style; Methadone; Narcotics; Neonatal Abstinence Syndrome; Outpatients; Postpartum Period; Pregnancy; Pregnancy Outcome; Prospective Studies; Severity of Illness Index

The main objective of this study was to analyze emotional response to a set of everyday emotional visual stimuli unrelated to drug use. Two groups of prescribed opiate drug abusers (heroin+methadone vs. methadone-only groups) currently participating in the Andalusian Experimental Prescribed Drug Program (Programa Experimental de Prescripcion de Estupefacientes de Andalucia, PEPSA) were studied, and comparisons made between them, within them for different phases, and between them and a normative group of nonusers. For this purpose we used the I.C.E.R.E., an instrument based on the I.A.P.S. (International Affective Picture System) and on Peter Lang's S.A.M. (Self-Assessment Manikin). The results showed patterns of emotional response in the opiate users, compared to the non-users, characterized by a lower rating of the everyday natural stimuli of a pleasant nature and a greater sensitivity to the stimuli of a neutral and negative nature. These patterns were quite stable even in different clinical situations and stages of development of the P.E.P.S.A.

Topics: Adult; Affect; Drug Prescriptions; Expressed Emotion; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Narcotics; Severity of Illness Index; Substance Abuse, Intravenous

Trials in Switzerland, the Netherlands and Spain have found that heroin-assisted treatment (HAT) as maintenance treatment for opioid-dependent patients reduces illicit drug use. A German trial also found diamorphine treatment to be superior to methadone treatment. The present study describes the association between 2 years of heroin treatment and improvements in health and social stabilization, as well as illicit drug use.. A prospective cohort study design.. A total of 515 patients were assigned to diamorphine treatment; 278 patients remained in the study treatment for the entire period of 24 months (54.8%).. The results on physical (Opiate Treatment Index Health Symptoms Scale) and mental (Symptom Checklist 90-Revised Global Severity Index) health and illicit drug use (number of days with drug use within the last month-European Addiction Severity Index) were examined by repeated-measures analyses.. Symptoms of physical (Pillai's trace = 0.837, df = 4, P < 0.001) and mental health (Pillai's trace = 0.450, df = 4, P < 0.001) improved during treatment. Street heroin use declined rapidly (Pillai's trace = 0.836, df = 4, P < 0.001), as did cocaine use (Pillai's trace = 0.280, df = 4, P < 0.001).. HAT is associated with improvements in mental and physical health in the long term.

Topics: Adult; Analgesics, Opioid; Female; Germany; Heroin; Heroin Dependence; Humans; Male; Methadone; Substance Abuse Treatment Centers; Time; Treatment Outcome

Persistent cue reactivity to drug-related stimuli is a well-known phenomenon among abstinent drug users and has been found to be a predictor of relapse. Cue exposure therapy (CET) aims to reduce this cue reactivity by exposing abstinent drug users to conditioned drug-related stimuli while preventing their habitual response, i.e. drug use.. 127 abstinent heroin-dependent Dutch inpatients were randomized to CET (n = 65; 55 completers) and placebo psychotherapy treatment (PPT) (n = 62; 59 completers). It was examined whether CET would lead to a decrease in drug-related cue reactivity (using mixed-design ANOVA) and subsequently to lower dropout and relapse rates (using logistic regression) compared to PPT.. Both groups responded with a similar decrease in self-reported cue reactivity (craving, mood). The CET group did show a significant decrease in physiological reactivity (skin conductance) compared to PPT. However, dropout and relapse rates were, contrary to our expectations, significantly higher in the CET group.. This is the first randomized controlled trial showing that CET, compared to a non-specific psychotherapy, might increase dropout and relapse rates among abstinent heroin-dependent clients in a drug-free setting. Caution is warranted when applying CET in this specific context.

Topics: Adult; Arousal; Cues; Desensitization, Psychologic; Female; Galvanic Skin Response; Heroin; Heroin Dependence; Humans; Male; Netherlands; Patient Dropouts; Psychotherapy; Secondary Prevention; Self Efficacy; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Treatment Failure

To determine annual patterns and correlates of nonfatal heroin overdose across 3 years, data were analyzed on 387 heroin users recruited for the Australian Treatment Outcome Study (ATOS), interviewed at 12, 24, and 36 months. A heroin overdose across follow-up was reported by 18.6%, and naloxone had been administered to 11.9%. Annual rates of overdose declined between baseline and 12 months and then remained stable. Previous overdose experience was strongly related to subsequent overdose. Those with a history of overdose before ATOS were significantly more likely to overdose during the study period. In particular, there was a strong association between overdose experience in any 1 year and increased overdose risk in the subsequent year. This is the first study to examine long-term annual trends in nonfatal heroin overdose. While overdose rates declined after extensive treatment, substantial proportions continued to overdose in each year, and this was strongly associated with overdose history.

Topics: Adolescent; Adult; Buprenorphine; Cohort Studies; Drug Overdose; Episode of Care; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Incidence; Interviews as Topic; Male; Methadone; Middle Aged; Naloxone; Needle-Exchange Programs; New South Wales; Substance Abuse Treatment Centers; Treatment Outcome

Sharing of drug paraphernalia to prepare, measure and divide drugs for injection remains an important residual risk factor for hepatitis C and other blood-borne infections among injection drug users (IDUs) especially as sharing of syringes for injection decreases.. We analyzed data from five U.S. cities to determine the prevalence and independent correlates of non-syringe paraphernalia-sharing (NSPS) and syringe-mediated drug-splitting (SMDS) among 15-30-year-old IDUs who reported not injecting with others' used syringes (receptive syringe-sharing, RSS).. NSPS was reported by 54% of IDUs who did not practice RSS and was independently associated (p<0.05) with having > or =5 injection partners, injecting with sex partners or regular injection partners, injecting in shooting galleries, peers' sharing behaviors, lower self-efficacy for avoiding NSPS, and less knowledge of HIV and HCV transmission. SMDS was reported by 26% of IDUs who did not practice RSS, and was independently associated with having > or =5 injection partners, injecting in shooting galleries, and inversely associated with unknown HIV status.. NSPS and SMDS were common among young adult IDUs. Increased efforts to prevent these risky practices should address social and environmental contexts of injection and incorporate knowledge and skills building, self-efficacy, and peer norms.

Topics: Adolescent; Adult; Analysis of Variance; Data Collection; Data Interpretation, Statistical; Female; Health Knowledge, Attitudes, Practice; Heroin; Heroin Dependence; Humans; Male; Narcotics; Needle Sharing; Patient Selection; Research Design; Risk Factors; Risk-Taking; Substance Abuse, Intravenous; United States; Urban Population

Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment.. This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs.. Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms.. A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.

Topics: Adult; Behavior Therapy; Buprenorphine; Combined Modality Therapy; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Naloxone; Patient Compliance; Patient Dropouts; Severity of Illness Index; Single-Blind Method; Substance Abuse Detection; Treatment Outcome

Although both the subjective and physiological effects of abused psychotropic substances have been characterized, less is known about their effects on brain function. We examined the actions of intravenous diacetylmorphine (heroin), the most widely abused opioid, on regional cerebral blood flow (rCBF), as assessed by perfusion-weighted MR imaging (PWI) in a double-blind and placebo-controlled setting.. Eight male subjects dependent of diacetylmorphine (mean age 36 years, range: 26 to 44 years), who had participated in a clinical diacetylmorphine maintenance program, underwent PWI with gadolinium injection. At two sessions separated by 2-7 days, the participants were examined 80 s after intravenous administration of either diacetylmorphine or saline. rCBF in four regions of interest (amygdala, vermis of the cerebellum, anterior cingulated cortex and thalamus) was compared with heroin versus placebo.. In the cerebellum, thalamus and cingulated cortex, there were no significant differences in perfusion values between diacetylmorphine and placebo. In the amygdala, perfusion values were 0.8+/-0.4 and 0.5+/-0.2 on the left, and 0.9+/-0.4 and 0.6+/-0.3 on the right, with diacetylmorphine and with placebo, respectively (t-test results were P=0.044 and P=0.033 on the left and right sides, respectively). Other differences in perfusion values between the drug and placebo did not reach statistical significance.. Perfusion MRI demonstrated differences in brain hemodynamics induced by drug intake.

Topics: Adult; Cerebrovascular Circulation; Cross-Over Studies; Diffusion Magnetic Resonance Imaging; Dose-Response Relationship, Drug; Double-Blind Method; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Narcotics

This open-label, noncomparative, single-center trial evaluated the safety and efficacy of once-daily treatment with slow release oral morphine (SROM) capsules for the maintenance treatment of 20 outpatients with heroin dependency over 6 months at the National Institute for Addictions in Sofia, Bulgaria. Doses were individually titrated up to a mean daily maintenance dose of 760 mg (range 440-1,200 mg). SROM was effective in significantly reducing the signs and symptoms of opioid withdrawal and craving for heroin, with stabilization generally evident within two weeks. Nineteen patients completed 6 months of treatment and illicit opioid use was virtually eliminated. One patient withdrew voluntarily at 22 weeks. Validated questionnaires and tests indicated improvements in patients' well-being from baseline assessments. These included significant improvements with regard to suicidal depression (85%), anxiety and dysphoria (66%), general illness (58%), social dysfunction (54%), sense of hopelessness (34%), attention (25%), and self-reported typical depressive (27%) and disease-related (11%) symptoms. No deaths, serious adverse events, or withdrawals due to adverse events occurred. Five episodes of constipation and one episode of sweating (all nonserious and of mild or moderate severity) were reported. Vital signs were unaffected by SROM and no weight change was evident over the study period. The observations made in this study indicate a promising role for once-daily treatment with SROM in the clinical management of heroin dependency.

Topics: Adult; Bulgaria; Capsules; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Morphine; Quality of Life; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Treatment Outcome

An intranasal (IN) diamorphine spray was investigated as a possible alternative to injectable diamorphine for maintenance treatment. Plasma morphine and 6-monoacetylmorphine (6MAM) concentrations and pharmacodynamic responses were measured for 4 h following intravenous (IV) and IN administration of 40 mg diamorphine in 4 patients prescribed injectable diamorphine. The two routes were primarily differentiated by the significantly greater speed and magnitude of peak plasma morphine and 6MAM concentrations for IV versus IN diamorphine. Beyond this initial peak, mean ratings suggested that withdrawal suppression and positive effects were at least as strong for IN compared to IV administration. All subjects gave favourable appraisals of the IN diamorphine spray, citing advantages including ease of use, the avoidance of needle hazards, and reduced stigma. IN administration may be an alternative or supplementary form of diamorphine maintenance and deserves serious further investigation.

Topics: Administration, Intranasal; Biological Availability; Cross-Over Studies; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Middle Aged; Morphine Derivatives; Narcotics; Substance Abuse Detection; Substance Withdrawal Syndrome

In several European countries and in Canada, clinical trials are being conducted in which heroin-addicted patients are treated with pharmaceutically prepared heroin in order to reduce the destructive behaviour that is so often associated with this drug.. To develop an integrated population pharmacokinetic model for heroin (diamorphine) and its pharmacodynamically active metabolites 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide. Additionally, the influence on heroin pharmacokinetics of several covariates that are typical for this population was determined.. Plasma concentration data from 106 heroin-dependent patients in The Netherlands (74 heroin inhalers and 32 injectors) were obtained. The 'chasing the dragon' technique was used for inhalation, in which the fumes of heroin base, heated on aluminum foil, were inhaled. Heroin doses varied between 66 and 450 mg. Heroin, 6-acetylmorphine and morphine data were fitted simultaneously using sequential two-compartment models. Morphine-3-glucuronide and morphine-6-glucuronide data were fitted separately to one-compartment models. All data analysis was performed using nonlinear mixed-effect modelling.. The bioavailability of inhaled heroin was estimated to be 53% (95% CI 43.7, 62.3). The terminal half-lives of heroin and 6-acetylmorphine were estimated to be 7.6 and 21.8 minutes, respectively. The clearances of morphine and the morphine-glucuronides were estimated to be 73.6 L/h (95% CI 62.8, 84.4) and between 6 and 10 L/h, respectively. The terminal half-life of 6-acetylmorphine was 13% lower in cocaine users (p < 0.05). No other significant relationships between covariates and pharmacokinetic parameters were discovered.. Pharmacokinetic parameters of heroin and its five major metabolites were assessed simultaneously in one integrated model. Covariate analyses revealed that sex, bodyweight, benzodiazepine use and creatinine clearance (>60 mL/min) do not need to be taken into account in the medical prescription of pharmaceutically prepared heroin for the treatment of heroin dependency.

Topics: Administration, Inhalation; Adult; Analgesics, Opioid; Biological Availability; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Middle Aged; Models, Biological; Morphine; Morphine Derivatives; Narcotics; Netherlands

Twelve-month treatment of heroin addicts with methadone or buprenorphine normalized plasma cortisol levels, and controlled withdrawal symptoms as well as craving. During treatment, the time course of plasma cortisol levels and craving was not strictly correlated: heroin craving was more elevated at 12 than at 3 months. The results suggest a correlation between hypercortisolism, withdrawal symptoms and heroin use and suppose a more complex role for craving and its components in drug-taking behaviour. The main goal of the pharmacological treatment of opioid-dependence should be addressed at the normalization of hypothalamic-pituitary-adrenocortical (HPA) axis more than at the control of craving.

Topics: Adult; Buprenorphine; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Methadone; Motivation; Narcotics; Pituitary-Adrenal System; Statistics as Topic; Substance Withdrawal Syndrome

Naltrexone is an opioid antagonist that is currently approved as a treatment for opioid and alcohol dependence. Although it is highly effective in completely antagonizing the effects of opioids, medication noncompliance is a difficult obstacle to treatment. Therefore, a sustained-release form of naltrexone may improve treatment outcome.. The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex).. Five heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, the effects of a range of heroin doses (0, 6.25, 12.5, and 25 mg, i.v.) were examined. Participants then received 384 mg naltrexone base. The effects of heroin were again evaluated for the next 6 weeks. One dose of heroin was tested per day and the entire dose range was tested each week. Doses were administered in non-systematic order. During a morning sample session, participants received a dose of heroin and $20 and subjective, performance, and physiological effects were measured both before and after drug administration. During an afternoon choice session, participants were given the opportunity to choose the sampled heroin dose and/or amount of money using a modified progressive ratio procedure.. Depot naltrexone antagonized both the reinforcing and subjective effects of heroin for 4-5 weeks. Subjective ratings of withdrawal were reduced after week 2 and throughout the remainder of the study. The effects of heroin on mean trough pupil diameter began to emerge by week 5. There were no clinically significant effects on respiratory or cardiovascular function.. The present results extend our previous findings by showing that the reinforcing effects of heroin were reduced for 4-5 weeks after administration of 384 mg depot naltrexone.

Topics: Adult; Affect; Cardiovascular System; Choice Behavior; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Heroin; Heroin Dependence; Humans; Liver; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Narcotics; Pupil; Self Administration; Time Factors; Token Economy

To assess the efficacy and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users.. An open-label, prospective cohort study with two non-randomly assigned treatment arms and historical controls: DAM tablets only versus DAM tablets combined with injected DAM and/or other opioids, with an observation period of 1 year.. Twenty-one out-patient treatment centres of the Swiss heroin-assisted treatment programme.. A total of 128 patients received DAM tablets only, and 237 patients received a combination of orally and intravenously applied DAM and other opioids.. Retention rate after 1 year; number of serious adverse events; dosage of DAM over time; subjective tolerance of study medication.. In the intention-to-treat analysis, 1-year retention rates after 1 year in the DAM tablets-only group [0.804, 95% confidence interval (CI) = 0.735-0.873] as well as in the subgroup combining oral application of DAM with intravenous application or other opioids (0.843, 95% CI = 0.797-0.889) were higher compared to historical controls (Swiss cohort of patients who had been substituted intravenously with DAM; 1-year retention rate = 0.70). Rates of serious adverse events under study medication (tablets only = 0.038 per application year; tablets in combination = 0.028 per application year) were comparable to the historical rate of the Swiss heroin-assisted treatment (0.043).. DAM tablets seem to be an effective and safe application mode of heroin-assisted substitution treatment. Randomized clinical trials to compare its relative efficacy to other substances are necessary.

Topics: Adult; Cohort Studies; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Prospective Studies; Substance Abuse, Intravenous; Treatment Outcome

This randomized placebo-controlled trial tested the efficacy of oral naltrexone with or without fluoxetine for preventing relapse to heroin addiction and for reducing HIV risk, psychiatric symptoms, and outcome. All patients received drug counseling with parental or significant-other involvement to encourage adherence. Patients totaling 414 were approached, 343 gave informed consent, and 280 were randomized (mean age, 23.6 +/- 0.4 years). At 6 months, two to three times as many naltrexone patients as naltrexone placebo patients remained in treatment and had not relapsed, odds ratio (OR) = 3.5 (1.96-6.12), p < .0001. Overall, adding fluoxetine did not improve outcomes, OR = 1.35 (0.68-2.66), p = .49; however, women receiving naltrexone and fluoxetine showed a trend toward a statistically significant advantage when compared to women receiving naltrexone and fluoxetine placebo, OR = 2.4 (0.88-6.59), p = .08. HIV risk, psychiatric symptoms, and overall adjustment were markedly improved among all patients who remained on treatment and did not relapse, regardless of group assignment. More widespread use of naltrexone could be an important addition to addiction treatment and HIV prevention in Russia.

Topics: Adult; Antidepressive Agents, Second-Generation; Combined Modality Therapy; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Heroin; Heroin Dependence; HIV Infections; Humans; Male; Naltrexone; Narcotic Antagonists; Psychotherapy; Russia; Secondary Prevention; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Although commonly assessed with unidimensional scales, craving has been suggested to be multifaceted and to have a complex relationship with drug use and relapse. This study assessed the consistency and predictive validity of unidimensional and multidimensional craving scales. At the beginning of a 12-week outpatient treatment trial, opiate users (n = 101) and cocaine users (n = 72) completed unidimensional visual analog scales (VASs) assessing "want," "need," and "craving" and multidimensional 14- and 45-item versions of the Cocaine Craving Questionnaire (CCQ) or Heroin Craving Questionnaire (HCQ). Spearman correlations between the VASs and the first-order factors from the 45-item CCQ/HCQ were .20-.40, suggesting that the two types of assessment were not redundant. Treatment dropout and in-treatment drug use were more frequently predicted by scores on the 14- or 45-item CCQ than by VAS ratings. Results suggest that the CCQ/HCQ and the 14-item CCQ provide information that unidimensional VASs do not.

Topics: Adult; Ambulatory Care; Cocaine; Cocaine-Related Disorders; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Motivation; Pain Measurement; Patient Dropouts; Personality Inventory; Psychometrics; Recurrence; Reproducibility of Results; Self Efficacy; Statistics as Topic; Substance Abuse Detection; Substance Withdrawal Syndrome; Surveys and Questionnaires; Treatment Refusal

To investigate which baseline patient characteristics of treatment-resistant heroin addicts differentially predicted treatment response to medical heroin prescription compared to standard methadone maintenance treatment.. Two open-label randomized controlled trials; pooled data.. Methadone maintenance programmes and heroin treatment centres in six cities in the Netherlands.. Four hundred and thirty heroin addicts.. Methadone plus injectable heroin or methadone plus inhalable heroin compared to methadone alone prescribed over 12 months: heroin maximum 1000 mg per day, methadone maximum 150 mg per day.. Dichotomous, multi-domain response index, including validated indicators of physical health, mental status and social functioning.. Data of the inhalable and injectable heroin trials were pooled. Intention-to-treat analysis showed that treatment with medically prescribed heroin plus methadone was significantly more effective (51.8% response) than standard methadone maintenance treatment (28.7%) (95% CI of response difference: 14.1-32.2%). Multivariate logistic regression analyses showed that only one of all baseline characteristics was predictive of a differential treatment effect: patients who had previously participated in abstinence-orientated treatment responded significantly better to heroin-assisted treatment than to methadone treatment (61% versus 24%), while patients without experience in abstinence-orientated treatment did equally well in heroin-assisted or methadone maintenance treatment (39% and 38%, respectively).. The effect of heroin-assisted treatment is not dependent on clinical characteristics, with the exception of previous abstinence-orientated treatment: medical prescription of heroin is most effective for those patients who have previously participated in abstinence-orientated treatment.

Topics: Administration, Inhalation; Adult; Drug Resistance; Female; Heroin; Heroin Dependence; Humans; Injections; Logistic Models; Male; Methadone; Narcotics; Netherlands; Patient Compliance; Regression Analysis

The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine and its dimethylxanthine metabolites were studied. The objectives were to establish the population pharmacokinetics under these exceptional circumstances and to compare the results to published data regarding intravenous and oral administration in healthy volunteers. Diacetylmorphine preparations containing 100 mg of caffeine were used by 10 persons by inhalation. Plasma concentrations of caffeine, theobromine, paraxanthine and theophylline were measured by high performance liquid chromatography. Non-linear mixed effects modelling was used to estimate population pharmacokinetic parameters. The model was evaluated by the jack-knife procedure. Caffeine was rapidly and effectively absorbed after inhalation. Population pharmacokinetics of caffeine and its dimethylxanthine metabolites could adequately and simultaneously be described by a linear multi-compartment model. The volume of distribution for the central compartment was estimated to be 45.7 l and the apparent elimination rate constant of caffeine at 8 hr after inhalation was 0.150 hr(-1) for a typical individual. The bioavailability was approximately 60%. The presented model adequately describes the population pharmacokinetics of caffeine and its dimethylxanthine metabolites after inhalation of the caffeine sublimate of a 100 mg tablet. Validation proved the stability of the model. Pharmacokinetics of caffeine after inhalation and intravenous administration are to a large extent similar. The bioavailability of inhaled caffeine is approximately 60% in experienced smokers.

Topics: Administration, Inhalation; Administration, Oral; Biological Availability; Caffeine; Central Nervous System Stimulants; Drug Combinations; Drug Interactions; Half-Life; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Methadone; Narcotics; Population; Theobromine; Theophylline

In preparation for a trial on co-prescription of inhalable heroin and methadone, two methods for inhalation of heroin/caffeine tablets were compared: the commonly used method of 'chasing the dragon' and a standardised procedure for inhalation of volatilised heroin, using a heating device. Five male addicts inhaled a tablet of smokable heroin daily for 5 days, alternating the inhalation method. Plasma concentrations of heroin, 6-acetylmorphine, morphine and morphine-3- and -6-glucuronide were determined using a liquid chromatography method with tandem mass spectrometric detection. The exposure to heroin and its metabolites (expressed as areas under the concentration-time curve) was significantly lower after smoking via the heating device than after 'chasing the dragon': heroin 80% and 6-acetylmorphine 73% lower (p < 0.05). Maximal concentrations of heroin and 6-acetylmorphine were also 80% and 70% lower (p < 0.05) after using the heating device. 'Chasing the dragon' is a more efficient inhalation method than inhalation via the heating device.

Topics: Administration, Inhalation; Adult; Caffeine; Central Nervous System Stimulants; Half-Life; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Psychiatric Status Rating Scales; Smoke

Although buprenorphine is effective in treating opioid dependence, optimal maintenance doses of buprenorphine or the buprenorphine/naloxone combination have not yet been established.. The present study was designed to evaluate the effects of buprenorphine/naloxone maintenance (2/0.5, 8/2, 32/8 mg sublingual) on the reinforcing and subjective effects of heroin (0, 12.5, 25, 50, and 100 mg intranasal) in heroin-dependent individuals.. During test weeks, participants (N=7) first sampled a dose of heroin and 20 dollars. During subsequent choice sessions, participants could choose to self-administer heroin and/or money. Participants responded under a modified progressive-ratio schedule (PR 50, ..., 2,800) during a ten-trial self-administration task.. Heroin break point values and subjective responses were significantly lower under 8/2 and 32/8 mg buprenorphine/naloxone compared to 2/0.5 mg. The self-administration and subjective effects data for heroin in the presence of buprenorphine/naloxone were compared to a separate control group of recently detoxified participants (N=8) in order to obtain estimates for the apparent in vivo dissociation constant (K(A)), the efficacy estimate (tau), and the estimated fraction of receptors remaining after buprenorphine/naloxone treatment (q). The apparent in vivo dissociation constant for heroin ranged from 50 to 126 mg (K(A)) and the efficacy estimate ranged from 13 to 20 (tau). In addition, 2/0.5, 8/2, and 32/8 mg buprenorphine/naloxone dose-dependently reduced the receptor population by 74, 83, and 91%, respectively.. These data demonstrate that both 8/2 and 32/8 mg buprenorphine/naloxone were well tolerated and effective in reducing the reinforcing and subjective effects of heroin, relative to the 2/0.5-mg dose. The data also show for the first time in humans that it is possible to quantify the efficacy and affinity of heroin for mu opioid receptors, and that 80-90% of mu receptors need to be inactivated in order to obtain significant reductions in heroin-induced effects. These results have important implications for future studies in which it will be possible to obtain estimates of relative affinity and efficacy of different agonists at mu opioid receptors.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Motivation; Naloxone; Narcotics; Reinforcement, Psychology; Substance Withdrawal Syndrome; Treatment Outcome

The purpose of the present study was to investigate cumulative heroin effects on brain functioning by studying relationships among electroencephalography (EEG) spectral power and mean frequencies and heroin abuse history. Eyes-closed resting EEG data were collected from the 19 monopolar electrode sites in 33 heroin abusers and 13 age-matched healthy volunteers. The mean age of the patients was 23.1+/-4.5 years, the duration of daily heroin abuse (DDHA) ranged from 4 to 44 months, the intravenous doses of heroin ranged from 0.04 to 1.00 g/day, the abstinence length ranged from 6 days to 4.5 months. General linear model (GLM) repeated measures procedure revealed a significant group effect on the distribution of the mean power spectrum between bands and mean frequencies in almost all analyzed derivations. Further analysis demonstrated that these intergroup differences were diversely related to at least three aspects of heroin-taking history. Frequency shifts in alpha2 range, most prominent in frontal and central derivations, were related to duration of daily heroin consumption. Slowing of alpha1 mean frequency, most prominent in central, temporal, and occipital derivations, was registered mainly in heroin addicts who abused high doses of the drug. Spectral power characteristics of brain electrical activities in our patient population were strongly predicted by abstinence length. The present results give grounds to suppose that chronic heroin-taking induces neuronal oscillation frequency changes, which may contribute to the development of antisocial trends and some semantic processes disturbances in these patients. Supplementary neurophysiological deficit is characteristic for heroin addicts who takes high doses of the drug, however, its relation to heroin abuse remains unclear. Pronounced desynchronization is observed in acute heroin withdrawal, and spectral power characteristics tend to normalize almost completely during several weeks of abstinence.

Topics: Adult; Electroencephalography; Heroin; Heroin Dependence; Humans; Linear Models; Male; Narcotics; Substance Withdrawal Syndrome; Time Factors

This study tested whether opiate dependence, tobacco smoking, or their combination accompanied impaired performance on the gambling task (GT), which tests decision-making. GT previously detected impairments in patients with lesions of the ventromedial prefrontal cortex and in substance abusers. Four groups were matched on demographic characteristics and intelligence: methadone-maintained smokers (n = 9) and nonsmokers (n = 9), and control (i.e., not opiate-dependent) smokers (n = 9) and nonsmokers (n = 10). The Wisconsin Card Sorting Task (WCST) was administered to test whether differences in GT performance reflected generalized deficits in prefrontal cortical function. While there were no significant group differences on the WCST, groups differed significantly on GT performance (F(3,31) = 2.95, P = 0.048), controlling for depressive symptom ratings and childhood attention deficit hyperactivity disorder. Methadone-maintained smokers (but not nonsmokers) performed more poorly than either of the two control groups (P = 0.007 versus smokers; P = 0.024 versus nonsmokers). In a planned analysis of methadone-maintained subjects, smokers scored more poorly on GT than nonsmokers (F(1,18) = 5.64, P = 0.032) and had more treatment failures (67% heroin use during the last 30 days versus 20%). The findings suggest that among opiate-dependent individuals, tobacco smoking may be a marker for a more severe form of substance abuse disorder, reflecting impaired decision-making, as modeled by GT.

Topics: Adult; Cocaine; Cocaine-Related Disorders; Comorbidity; Decision Making; Female; Gambling; Heroin; Heroin Dependence; Humans; Los Angeles; Male; Middle Aged; Neuropsychological Tests; Prefrontal Cortex; Prospective Studies; Psychometrics; Reference Values; Smoking; Substance Abuse Treatment Centers

Gabapentin is an antiepileptic drug shown to be effective in the treatment of pain disorders and appears to be useful as well for several psychiatric disorders, including bipolar disorder, anxiety disorders, alcohol withdrawal and cocaine dependence. Gabapentin, at a dose of 600 mg three times a day, was evaluated as an add-on medication to a standard detoxification regime in seven heroin dependent individuals undergoing outpatient opiate withdrawal treatment. All seven patients successfully completed opiate detoxification and commenced opiate antagonist treatment with naltrexone on day five of withdrawal treatment, as scheduled. No adverse event was noted. Gabapentin appeared to lead a reduction in symptomatic medication and an overall beneficial effect on symptoms of heroin withdrawal.

Topics: Acetates; Adult; Amines; Cyclohexanecarboxylic Acids; Excitatory Amino Acid Antagonists; Female; Gabapentin; gamma-Aminobutyric Acid; Heroin; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Narcotics; Recurrence; Substance Withdrawal Syndrome

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.

Topics: Acoustic Stimulation; Adult; Cues; Electrooculography; Event-Related Potentials, P300; Female; Heroin; Heroin Dependence; Humans; Male; Memory, Short-Term; Mental Recall; Narcotics; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychomotor Performance; Substance Withdrawal Syndrome

Clinical observations and recent findings suggested different acceptance of morphine and heroin by intravenous drug users in opiate maintenance programs. We postulated that this is caused by differences in the perceived effects of these drugs, especially how desired and adverse effects of both drugs interacted.. We measured the desired and adverse effects of high doses of injected morphine and heroin in patients to determine the causal interactions between both types of effects and test the hypothesis of a differential mechanism of action.. Thirty-three patients (five females, 28 males; mean duration of previous street heroin use 10.7 years, mean age 30.1 years) were randomly allocated double-blind to the substance groups. The average daily dose per participant in the heroin condition (n=17) was 491 mg, in the morphine condition (n=16) 597 mg. The observation period lasted 3 weeks; an average of 70 injections was received. After each injection of either substance, various aspects of drug effects were recorded systematically. Ratings were summarized into the factors "euphoria" and "adverse effects". Time series models were computed for each participant on the basis of the factor scores, using vector autoregression (VAR).. A highly significant difference between the substances was found in the interaction between "euphoria" and "adverse effects". Adverse effects of heroin preceded higher euphoria, whereas adverse effects of morphine preceded subsequent lower euphoria. Additionally, the finding of a higher level of adverse effects in morphine was replicated.. Results point to different mechanisms of action of the two opioids when the perceived drug effects are evaluated in a field setting. This may explain the better acceptance of heroin in opiate-assisted treatment of intravenous drug patients. The method used can be a valuable tool for the comparison of substance groups other than opioids.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Euphoria; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Morphine Dependence; Patient Acceptance of Health Care; Substance Abuse, Intravenous

To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment.. Two open label randomised controlled trials.. Methadone maintenance programmes in six cities in the Netherlands.. 549 heroin addicts.. Inhalable heroin (n = 375) or injectable heroin (n = 174) prescribed over 12 months. Heroin (maximum 1000 mg per day) plus methadone (maximum 150 mg per day) compared with methadone alone (maximum 150 mg per day). Psychosocial treatment was offered throughout.. Dichotomous, multidomain response index, including validated indicators of physical health, mental status, and social functioning.. Adherence was excellent with 12 month outcome data available for 94% of the randomised participants. With intention to treat analysis, 12 month treatment with heroin plus methadone was significantly more effective than treatment with methadone alone in the trial of inhalable heroin (response rate 49.7% v 26.9%; difference 22.8%, 95% confidence interval 11.0% to 34.6%) and in the trial of injectable heroin (55.5% v 31.2%; difference 24.3%, 9.6% to 39.0%). Discontinuation of the coprescribed heroin resulted in a rapid deterioration in 82% (94/115) of those who responded to the coprescribed heroin. The incidence of serious adverse events was similar across treatment conditions.. Supervised coprescription of heroin is feasible, more effective, and probably as safe as methadone alone in reducing the many physical, mental, and social problems of treatment resistant heroin addicts.

Topics: Adult; Aged; Directly Observed Therapy; Drug Resistance; Heroin; Heroin Dependence; Humans; Methadone; Middle Aged; Narcotics; Patient Compliance

The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p < 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p < 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.

Topics: Adolescent; Adult; Anesthesia, General; Female; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Methadone; Narcotic Antagonists; Prospective Studies; Severity of Illness Index; Substance Withdrawal Syndrome; Surveys and Questionnaires

In several countries medical prescription of diacetylmorphine is currently being evaluated as a treatment option for heavily dependent narcotic addicts. Because of damaged veins, many patients administer diacetylmorphine intramuscularly or orally. Therefore we characterized the pharmacokinetics of intramuscular and oral diacetylmorphine in the high dose range usually required in narcotic addicts.. Three intramuscular doses, 3 oral doses, and 1 intravenous dose of diacetylmorphine and oral and intravenous test doses of deuterium-labeled morphine (morphine-N-methyl-d3 [morphine-d3]) were administered to 8 heroin-addicted patients. Arterial plasma concentrations of diacetylmorphine, monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, and morphine-d3 were measured by liquid chromatography-mass spectrometry.. Intramuscularly administered diacetylmorphine (

Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Female; Half-Life; Heroin; Heroin Dependence; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Metabolic Clearance Rate; Narcotics

This study sought to characterize antagonist-precipitated heroin withdrawal during and immediately following anaesthesia and to identify the determinants of withdrawal severity and duration in 48 dependent heroin users. Objective withdrawal signs decreased significantly with each naloxone bolus administered under anaesthetic. The cost (amount) of the final heroin administration and the number of hours between last heroin use and commencement of anaesthesia were significant, independent predictors of the severity of withdrawal symptomatology. While 83% (40/48) of participants completed withdrawal according to objective criteria and commenced maintenance naltrexone treatment, almost half (22/48) were unable to commence naltrexone on the day of the procedure due to residual withdrawal signs. Fourteen of these 22 participants subsequently commenced naltrexone (median number of days between admission and commencement of naltrexone was 2, range 1 - 6) while eight left treatment prior to initiation of naltrexone. Significantly fewer of those with more severe withdrawal signs during anaesthesia commenced naltrexone (40% vs. 60%). While the severity and duration of withdrawal symptomatology may be moderated by encouraging participants to reduce (or cease) heroin use close to the time of withdrawal, for a substantial proportion of participants in this study, heroin withdrawal by this antagonist-precipitated procedure was neither rapid nor painless. [Ali R, Thomas P, White J, McGregor C, Danz,C, Gowing L, Stegink A, Athanasos P. Antagonist-precipitated heroin withdrawal under anaesthetic prior to maintenance naltrexone treatment: determinants of withdrawal severity.

Topics: Adolescent; Adult; Female; Heroin; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Severity of Illness Index; Substance Withdrawal Syndrome; Surveys and Questionnaires

Naltrexone, an opioid antagonist, is currently approved as a treatment for heroin dependence. However, naltrexone is generally not well accepted by patients, and medication non-compliance is a difficult obstacle to treatment. A sustained-release form of naltrexone may improve compliance.. The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex).. Twelve heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, six participants received 192 mg naltrexone base and six participants received 384 mg naltrexone base. For safety, the low dose of depot naltrexone was tested before the high dose. The effects of heroin (0, 6.25, 12.5, 18.75, 25 mg, i.v.) were evaluated for the next 6 weeks. One dose of heroin was tested per day on Mondays through Fridays, and the entire dose range was tested each week. Active heroin doses were administered in ascending order during the week, while placebo could be administered on any day. Subjective, performance, and physiological effects were measured both before and after heroin administration. The hypotheses were that depot naltrexone would antagonize the effects of heroin, and that the high dose of depot naltrexone would produce a more effective and longer-lasting antagonism than the low dose.. The low and high doses of depot naltrexone antagonized heroin-induced subjective ratings for 3 and 5 weeks, respectively. Plasma levels of naltrexone remained above 1 ng/ml for approximately 3 and 4 weeks after administration of 192 mg and 384 mg naltrexone. Other than the initial discomfort associated with the injection of depot naltrexone, there were no untoward side-effects.. These results suggest that this depot formulation of naltrexone provides a safe, effective, long-lasting antagonism of the effects of heroin.

Topics: Adult; Affect; Analysis of Variance; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Naltrexone; Narcotic Antagonists; Narcotics; Pupil

Several sources indicate that intravenously administered buprenorphine may have significant abuse liability in humans. The present study evaluated the reinforcing effects of intravenously administered buprenorphine (0, 2, and 8 mg) in detoxified heroin-dependent participants during a 7.5-week inpatient study. Participants (n = 6) were detoxified from heroin over a 1.5-week period immediately after admission. Testing subsequently occurred in three 2-week blocks. During the first week of each 2-week block, the reinforcing effects of buprenorphine were evaluated. Participants first received a dose of buprenorphine and $20 and then were given either the opportunity to self-administer the dose or $20 during choice sessions. During the second week of each 2-week block, the direct effects of heroin were measured to evaluate potential long-lasting antagonist effects of buprenorphine. Progressive ratio break-point values were significantly higher after 2 and 8 mg of buprenorphine compared with placebo. Correspondingly, several positive subjective ratings increased after administration of active buprenorphine relative to placebo. Although there were few differences in peak effects produced by 2 versus 8 mg of buprenorphine, the higher buprenorphine dose generally produced longer-lasting effects. Heroin also produced dose-related increases in several subjective effects. Peak ratings produced by heroin were generally higher than peak ratings produced by buprenorphine. There was little evidence of residual antagonism produced by buprenorphine. These results demonstrate that buprenorphine served as a reinforcer under these conditions, and that it may have abuse liability in nonopioid-dependent individuals who abuse heroin.

Topics: Adult; Attention; Blood Pressure; Buprenorphine; Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Humans; Male; Narcotics; Psychomotor Performance; Pupil; Reinforcement, Psychology; Substance Abuse, Intravenous; Time Factors

The aim of this study was to assess the safety of buprenorphine administered intravenously for the treatment of opioid withdrawal in medically ill hospitalized patients. Data regarding demographic information, number of doses of buprenorphine, and measures of buprenorphine's effects were collected via chart reviews for 30 heroin-dependent patients who received buprenorphine intravenously during their hospitalization for an acute medical problem. No respiratory depression was observed, and no patients reported feeling "high." All patients reported that buprenorphine decreased withdrawal symptoms. Thus, intravenous administration of buprenorphine appears to be safe for the treatment of opioid withdrawal.

Topics: Acute Disease; Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Middle Aged; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Drug Prescriptions; Heroin; Heroin Dependence; Humans; Methadone; Netherlands; Substance Abuse, Intravenous

Studies have shown that buprenorphine, a partial mu opioid agonist, effectively reduces heroin taking. While previous research with buprenorphine utilized a liquid formulation, a tablet formulation is proposed for clinical use. However, because recent research suggests that the liquid and tablet differ in bio-availability, it is unclear what dose of the buprenorphine tablet effectively antagonizes the reinforcing effects of heroin.. The present study was designed to compare the effects of two sublingual doses of buprenorphine maintenance on heroin self-administration.. Eight heroin-dependent men participated in a 6-week, double-blind, placebo-controlled inpatient study to evaluate the reinforcing effects of intravenous heroin (0, 6.25, 12.5, 25 mg) during maintenance on 8 or 16 mg sublingual buprenorphine. Participants first sampled the available dose of heroin, and then were allowed to respond under a progressive ratio schedule for either heroin or $20. For each heroin dose, one sample session and three choice sessions occurred. Two sessions per day were conducted. A sample session was followed by the first choice session on one day, and the second and third choice sessions occurred on the following day. These sessions were conducted while participants were maintained on daily doses of 8 or 16 mg buprenorphine (3 weeks each).. Relative to placebo, 12.5 and 25 mg heroin produced significant increases in break point values under both maintenance dose conditions. The mean break point value for 12.5 mg heroin was significantly lower under 16 mg buprenorphine, compared to 8 mg.. These results demonstrate that the reinforcing effects of heroin were not fully antagonized by these doses of the tablet formulation of buprenorphine, and that 16 mg buprenorphine reduced heroin self-administration relative to 8 mg.

Topics: Administration, Sublingual; Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Narcotic Antagonists; Narcotics; Psychomotor Performance; Pupil; Self Administration; Tablets

In Switzerland, medical prescription of heroin (diacetylmorphine) is currently being evaluated as a treatment option for heavily dependent addicts. Therefore the diacetylmorphine pharmacokinetics in opioid-addicted patients was studied.. Three different diacetylmorphine doses (up to 210 mg) and 20 mg deuterium-labeled morphine (morphine-d3) were administered intravenously to 8 heroin-addicted patients. Arterial and venous plasma samples were collected, and diacetylmorphine, monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, and morphine-d3 plasma concentrations were measured by liquid chromatography-mass spectrometry.. Maximal arterial concentrations of diacetylmorphine, monoacetylmorphine, and morphine were 2.4, 5.4, and 1.4 times higher and occurred 2 to 3 minutes earlier than maximal venous concentrations. Venous areas under the concentration-time curves (AUC) of diacetylmorphine and monoacetylmorphine were 35% and 26% lower than arterial AUC values, whereas for morphine the venous AUC was 15% higher. Morphine-3-glucuronide and morphine-6-glucuronide exhibited no arteriovenous differences. AUCs for diacetylmorphine, monoacetylmorphine, and morphine increased linearly with dose. Diacetylmorphine was completely metabolized to morphine. Substantial morphine input into the arterial circulation persisted for up to 90 minutes. The arterial clearances of diacetylmorphine, monoacetylmorphine, and morphine-d3 were 8.7 +/- 2.6, 6.7 +/- 1.6, and 2.3 +/- 0.3 L/min, respectively. The arterial half-lives of diacetylmorphine and morphine-d3 were 2. 4 +/- 0.8 and 88 +/- 21 minutes, respectively.. These data indicate that substantial arteriovenous differences exist for diacetylmorphine and metabolite kinetics, that the pharmacokinetics of diacetylmorphine and metabolites is linear even in the high dose range used by opioid addicts, and that not only diacetylmorphine but also monoacetylmorphine is substantially metabolized peripherally to morphine.

Topics: Adult; Analgesics, Opioid; Area Under Curve; Biotransformation; Dealkylation; Female; Half-Life; Heroin; Heroin Dependence; Humans; Injections, Intra-Arterial; Injections, Intravenous; Kidney; Liver; Male; Regional Blood Flow

In the Netherlands the total number of heroin addicts amounts to approximately 25,000. Of these about 70% is in contact with the treatment system. The remaining 30% have not been seeking help, believes that no help is needed or has lost faith in a better future altogether. Of those who are in treatment, 30% attempt to stop the use of opiates through participation in drug free abstinence oriented outpatient or inpatient treatment programs. The remaining 70% have given up the outlook of a drug free existence at least temporarily, and they participate in a methadone maintenance program directed at stabilizing drug use, harm minimization and social integration. In two-thirds these goals are not or only partially achieved. For these patients additional treatment options are needed. Medical prescription of heroin is such an option. However, currently no data are available on the effectiveness of this option. The Dutch study on the effectiveness of medical prescription of heroin is an attempt to obtain these data. In the study, simultaneously two randomized trials are being executed: one with inhalable and one with injectable heroin. In these trials, 625 (375 inhalers and 250 injectors) chronic treatment-resistant heroin addicts who are currently enrolled in a methadone maintenance program are offered heroin (in combination with oral methadone) seven days per week, three times per day for a period of six to twelve months. It is a multi-center study with eight treatment units in six cities in the Netherlands (Amsterdam, The Hague, Groningen, Heerlen, Rotterdam, Utrecht). At this moment 180 patients have been randomized. During the treatment no medical complications have been observed and no serious public order or safety problems have occurred. Study participants have been very compliant both with the treatment regimen and the research requirements. The latter is indicated by the fact that 85% of all the two-monthly assessments have been completed.

Topics: Administration, Inhalation; Drug Prescriptions; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Methadone; Narcotics; Netherlands; Patient Compliance

Groups of subjects whose primary drug of abuse was amphetamine or heroin were compared, together with age- and IQ-matched control subjects. The study consisted of a neuropsychological test battery which included both conventional tests and also computerised tests of recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting. Many of these tests have previously been shown to be sensitive to cortical damage (including selective lesions of the temporal or frontal lobes) and to cognitive deficits in dementia, basal ganglia disease, and neuropsychiatric disorder. Qualitative differences, as well as some commonalities, were found in the profile of cognitive impairment between the two groups. The chronic amphetamine abusers were significantly impaired in performance on the extra-dimensional shift task (a core component of the Wisconsin Card Sort Test) whereas in contrast, the heroin abusers were impaired in learning the normally easier intra-dimensional shift component. Both groups were impaired in some of tests of spatial working memory. However, the amphetamine group, unlike the heroin group, were not deficient in an index of strategic performance on this test. The heroin group failed to show significant improvement between two blocks of a sequence generation task after training and additionally exhibited more perseverative behavior on this task. The two groups were profoundly, but equivalently impaired on a test of pattern recognition memory sensitive to temporal lobe dysfunction. These results indicate that chronic drug use may lead to distinct patterns of cognitive impairment that may be associated with dysfunction of different components of cortico-striatal circuitry.

Topics: Adolescent; Adult; Amphetamine-Related Disorders; Amphetamines; Analysis of Variance; Attention; Chronic Disease; Cognition Disorders; Female; Heroin; Heroin Dependence; Humans; Language Tests; Male; Memory; Middle Aged; Neuropsychological Tests; Pattern Recognition, Visual; Reaction Time; Set, Psychology

The adrenergic system has long been known to be activated in a situation of stress and thus during opiate withdrawal. A method for detoxification that decreases the stimulation of the sympathetic nervous system will prevent changes of catecholamine levels. Some of such methods have been developed. One of them uses direct transition from heroin to oral naltrexone after deep sedation with midazolam in conjunction with naloxone, droperidol, ondansetron, and clonidine treatment for 24 hours. Can such method prevent adrenergic changes? Moreover, 5-HT has been related to mood disorders. This study aims to determine plasma catecholamines and 5-HT before heroin withdrawal, during the day of the withdrawal, and at the ends of the first day, the first week, and the first 6 months. Forty-three patients with more than 6 years of drug abuse volunteered to seek help to detoxify. After clinical evaluation, blood samples were taken. Plasma catecholamines were isolated by standard alumina procedures and measured by high-performance liquid chromatography with electrochemical detection. Only for NE was there a significant decrease in the day of heroin withdrawal with deep sedation, followed the next day by an increase. During the following days, NE plasma concentrations returned slowly to basal levels. Epinephrine and dopamine plasma levels did not significantly change. Platelet 5-HT levels progressively decreased from the day before detoxification until the last period of observation. We also found that there were no abrupt changes in cardiovascular functions. In conclusion, our results suggest that this type of ultrarapid opiate detoxification prevents the dramatic activation of the autonomic nervous system.

Topics: Adult; Analysis of Variance; Catecholamines; Drug Administration Routes; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Naloxone; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome; Systole; Treatment Outcome

1. To determine whether naltrexone-accelerated detoxification with minimal sedation is an acceptable and effective form of induction onto naltrexone. 2. To monitor outcomes of detoxified patients.. Observational study.. Medical ward of a general hospital (for detoxification) and a community clinic (for follow-up) in Sydney, NSW, 1998.. 15 heroin users and 15 people seeking withdrawal from methadone.. Detoxification used naltrexone (12.5 or 50 mg), with flunitrazepam (2-3 mg), clonidine (150-750 micrograms) and octreotide (300 micrograms) for symptomatic support. Patients remained awake and were discharged when they felt well enough. Follow-up was daily for four days and then weekly for up to three months for supportive care.. Acute side effects; patient ratings of severity and acceptability of withdrawal; nights of hospitalisation; rates of induction onto naltrexone; retention in treatment over three months; and relapse to opioid use.. Acute withdrawal with delirium lasted about four hours. Octreotide was crucial for controlling vomiting; with octreotide no patient required intravenous fluids. There were no major complications. Eighteen patients (60%) reported that it was a "quite" acceptable procedure, 18 (60%) required only one night's hospitalisation, and 24 (80%) were successfully inducted onto naltrexone (defined as taking naltrexone on Day 8). Three months later, six (20%) were still taking naltrexone (with four of these occasionally using heroin) and seven (23%) were abstinent from opioids, including five not taking naltrexone. Eleven had gone onto methadone maintenance, seven had relapsed to heroin use, and one had died of a heroin overdose.. Rates of induction onto naltrexone were comparable with those reported for accelerated detoxification under sedation, suggesting that it can be performed successfully with minimal sedation. As in other studies of naltrexone maintenance, retention was low, and relapse to heroin use was common.

Topics: Adolescent; Adult; Analgesics; Anti-Anxiety Agents; Clonidine; Conscious Sedation; Female; Flunitrazepam; Heroin; Heroin Dependence; Hormones; Humans; Male; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Narcotics; Octreotide; Pilot Projects; Substance Withdrawal Syndrome; Time Factors

This double-blind, randomized, placebo-controlled clinical trial evaluated the impact on withdrawal symptoms of (i) combining naltrexone with a 4-day buprenorphine taper for short opioid detoxification (NB Group), compared to (ii) using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For the NB Group (n = 32) escalating doses of oral naltrexone were given on days 2-8 (placebo day 1). For the PB Group (n = 28) placebo was given on days 1-7 and naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32 patients in the NB group, 59% experienced clinically relevant withdrawal (defined as OOW > or = 5) on day 2, but, after day 5, none experienced withdrawal. In the PB group, the number of patients experiencing withdrawal increased over time. The first naltrexone dose induced comparable withdrawal in both groups: peak OOW scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NB group, and 4.0 +/- 3.9 on day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NB group and none in the PB group, while only one patient dropped out in the PB group on day 8. Throughout the 8-day study, patients in both groups received similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs 0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives (up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity, suggesting that naltrexone combined with buprenorphine is an acceptable and safe treatment for shortened opioid detoxification and induction of naltrexone maintenance.

Topics: Adult; Analgesics; Area Under Curve; Buprenorphine; Clonidine; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

The objective of this article is to critique a study conducted by the Swiss Federal Office of Public Health to evaluate Switzerland's heroin maintenance project. Heroin abusers (N = 1,146) were enrolled in 18 research clinics. Subjects were recruited into three study arms--heroin, morphine, or methadone maintenance, but randomization was unsuccessful, and all received heroin. Medications were self-administered by injection on site. Patients were interviewed at intake and 6-month intervals up to 18 months. A review of the study revealed design weaknesses, including the absence of control groups, lack of corroboration of self-reports, failure to control for the influence of social services on outcome, and the absence of follow-up on those who left the trial prematurely. The program's ability to avert human immunodeficiency virus (HIV) transmission could not be fully evaluated because patients did not consistently submit to HIV testing. The Swiss trials of supervised heroin prescription trials do not withstand scientific scrutiny.

Topics: Adult; Drug Prescriptions; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Morphine; Outcome and Process Assessment, Health Care; Research Design; Switzerland

Five heroin-dependent research volunteers, maintained on divided daily oral morphine doses, participated in an inpatient study designed to evaluate intravenous (i.v.) heroin self-administration when money ($10, $20 or $40) was concurrently available. Each morning participants received a single injection of heroin (placebo, 6.25, 12.5, 25, or 50 mg/70 kg, i.v.) and each afternoon, they had the opportunity to self-administer all or part of the morning dose. Participants responded under a progressive-ratio schedule (50, 100, ..., 2800) during a 10-trial self-administration task. During each trial, participants could respond for 1/10th of the sampled heroin dose or 1/10th of a single money value. The progressive-ratio value increased independently for each option. The total amount of heroin and/or money chosen during the self-administration task was administered at the end of the task. Heroin dose-dependently increased ratings of 'good drug effect' and 'high', impaired task performance and decreased pupil diameter and blood oxygen saturation. Heroin also dose-dependently increased progressive-ratio break point values, which varied as a function of the alternative money amount. Consistent with previous studies, the present results demonstrate that alternative reinforcers, depending on magnitude, are effective in reducing heroin use in opioid-dependent individuals.

Topics: Administration, Oral; Adult; Blood Pressure; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Morphine; Narcotics; Psychomotor Performance; Reinforcement, Psychology; Self Administration; Substance Abuse, Intravenous; Surveys and Questionnaires; Token Economy

Topics: Adult; Delta Sleep-Inducing Peptide; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Self-Assessment; Substance Withdrawal Syndrome

To evaluate an experimental heroin maintenance programme.. Randomised trial.. Outpatient clinic in Geneva, Switzerland.. Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments.. Patients in the experimental programme (n=27) received intravenous heroin and other health and psychosocial services. Control patients (n=24) received any other conventional drug treatment (usually methadone maintenance).. Self reported drug use, health status (SF-36), and social functioning.. 25 experimental patients completed 6 months in the programme, receiving a median of 480 mg of heroin daily. One experimental subject and 10 control subjects still used street heroin daily at follow up (difference 44%; 95% confidence interval 16% to 71%). Health status scores that improved significantly more in experimental subjects were mental health (0.58 SD; 0.07 to 1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences. There were no benefits in terms of work, housing situation, somatic health status, and use of other drugs. Unexpectedly, only nine (38%) control subjects entered the heroin maintenance programme at follow up.. A heroin maintenance programme is a feasible and clinically effective treatment for heroin users who fail in conventional drug treatment programmes. Even in this population, however, another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids.

Topics: Adult; Ambulatory Care; Female; Follow-Up Studies; Health Status; Heroin; Heroin Dependence; Humans; Illicit Drugs; Income; Infusions, Intravenous; Interpersonal Relations; Male; Narcotics; Switzerland

Conflicting results, both decreased and increased, have been reported concerning the function of T-lymphocytes in heroin addicts. We investigated the alterations of T-lymphocyte proliferative responses and immunophenotypic markers on lymphoid cells in heroin addicts and during different periods of heroin withdrawal in addicted subjects. This study has demonstrated a decrease in the response of T-lymphocytes to 1.2, 2.5, 5 and 10 microg/ml of phytohemagglutinin stimuli in heroin addicts and 1- to 5-day heroin withdrawal subjects compared with controls. Similarly, in an in vitro study, 10(-4), 10(-6) and 10(-8) M concentrations of morphine were shown to suppress 0.6 and 2.5 microg/ml of PHA-stimulated T-lymphocyte obtained from naive subjects. This inhibitory effect of morphine on PHA stimulation was completely abolished by 100 microM naloxone. The immunological parameters of total T-lymphocytes (CD3), T-helper cells (CD4), cytotoxic T-cells (CD8), B-cells and natural killer cells that are the immunophenotypic markers studied by flow cytometric analysis were altered in heroin addicts, 15- to 21-day and 6- to 24-month heroin withdrawal subjects, when compared with controls. These results suggest that heroin addicts and short period (15 to 21 days and 6 to 24 months) of heroin withdrawal have decreases in their immune system functioning and that the heroin withdrawal subjects seem to gradually reverse their immunological parameters to normal levels when withdrawal was sustained >/=2 years. This is the first report examining immune function in heroin withdrawal subjects using the "cold turkey" method. The results are beneficial for further study of the mechanism responsible for the opioid-induced changes in immune function.

Topics: Adult; B-Lymphocytes; Female; Flow Cytometry; Fluorescent Antibody Technique, Direct; Heroin; Heroin Dependence; Humans; Lymphocyte Count; Male; Narcotics; Phytohemagglutinins; Substance Withdrawal Syndrome; T-Lymphocytes; Time Factors

To compare the clinical efficacy of different doses of levomethadyl acetate hydrochloride (known as LAAM) in the treatment of opioid dependence.. A randomized controlled, double-blind, parallel group, 17-week study.. Outpatient facilities at Johns Hopkins University Bayview Medical Center, Baltimore, Md.. Opioid-dependent volunteers (N=180) applying to a treatment-research clinic.. Thrice-weekly (Monday/Wednesday/Friday) oral LAAM dose conditions of 25/25/35 mg, 50/50/70 mg, and 100/100/140 mg and nonmandatory counseling.. Retention in treatment, self-reported heroin use, and opioid-positive urine specimens.. Retention was independent of subjects' sex and dose. Self-reported heroin use decreased in a dose-related manner. At final assessment, patients in the high-dose condition reported using heroin 2.5 of 30 days as compared with 4.1 or 6.3 days for patients in the medium-dose and low-dose conditions, respectively (high dose vs low dose, P<.05); urinalysis results were similarly dose related. Overall, 20 (34%) of 59 patients in the high-dose condition remained opioid-abstinent for 4 consecutive weeks, as compared with 8 (14%) of 59 in the medium-dose and 7 (11%) of 62 in the low-dose conditions (P<.01). Self-report and urinalysis data are consistent with a greater than 90% reduction in illicit opioid use by the high-dose group relative to pretreatment levels.. Opioid substitution treatment with LAAM substantially reduces illicit opioid use. The clinical efficacy of LAAM is positively related to dose.

Topics: Adult; Analysis of Variance; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin; Heroin Dependence; Humans; Male; Methadyl Acetate; Middle Aged; Narcotics; Substance-Related Disorders; Treatment Outcome

Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients.. To compare three pharmacologic protocols for opioid detoxification in a primary care setting.. Randomized, double-blind clinical trial with random assignment to treatment protocols.. A free-standing primary care clinic affiliated with drug treatment programs.. 162 heroin-dependent patients.. Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine.. Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms.. Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone.. Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups.

Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Buprenorphine; Clonidine; Double-Blind Method; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Primary Health Care; Substance Withdrawal Syndrome

For many years, toxicologists have detected the presence of drugs of abuse in biological materials using blood or urine. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples such as sweat. In a study conducted in a detoxification center, sweat patches were applied to 20 known heroin abusers. Subjects wore the patch with minimal discomfort for five days. During the same period, two urine specimens were also collected. Target drugs analyzed either by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) included opiates (heroin, 6-monoacetylmorphine, morphine, codeine), cocaine (cocaine, benzoylecgonine, ecgonine methyl ester), delta 9-tetrahydrocannabinol, benzodiazepines (nordiazepam, oxazepam), amphetamines (amphetamine, methamphetamine, methylenedioxyamphetamine [MDA], methylenedioxymethamphetamine [MDMA], methylenedioxyethylamphetamine [MDEA]), and buprenorphine. Patches were positive for opiates in 12 cases. Heroin (37-175 ng/patch) and/or 6-acetylmorphine (60-2386 ng/patch) were identified in eight cases, and codeine exposure (67-4018 ng/patch) was determined in four cases. When detected, heroin was always present in lower concentrations than 6-acetylmorphine, which was the major analyte found in sweat. Cocaine (324 ng/patch) and metabolites were found in only one case. delta 9-Tetrahydrocannabinol (4-38 ng/patch) was identified in nine cases. Benzodiazepine concentrations were very low, ranging from 2 to 44 and from 2 to 15 ng/patch for nordiazepam and oxazepam, respectively. MDEA (121 ng/patch) and its metabolite, MDA (22 ng/patch), were detected in one case. Buprenorphine, which was administered as therapy under close medical supervision, was detected in the range 1.3-153.2 ng/patch with no apparent relationship between the daily dose and amount excreted in sweat. All the urine tests were consistent with the sweat findings, but to identify the same drugs it was necessary to test two urine specimens along with only one sweat specimen. It was concluded that sweat testing appears to offer the advantage of being a relatively noninvasive means of obtaining a cumulative estimate of drug exposure over the period of a week. This new technology may find useful applications in the treatment and monitoring of substance abusers, as the patch provides a long-term continuous monitor of drug exposure or noncompliance.

Topics: Amphetamines; Benzodiazepines; Buprenorphine; Cannabinoids; Chromatography, High Pressure Liquid; Cocaine; Codeine; Dose-Response Relationship, Drug; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Illicit Drugs; Morphine; Morphine Derivatives; Reproducibility of Results; Sweat

Our investigation was carried out in subjects intoxicated with heroin or heroin mixtures to find out the time interval during which delayed life-threatening complications become manifest, such as pulmonary oedema or relapse into respiratory depression or coma after naloxone treatment. We studied prospectively all drug intoxications between 1991 and 1992. Of the 538 intoxications, we assessed in detail 160 outpatients who lived within the catchment area of our hospital. The outcome variables studied were (1) rehospitalization for pulmonary oedema, (2) relapse into coma, and/or (3) death and cause within 24 h after release from hospital. Deaths occurring outside our hospital have to be reported, as decreed by law, to the Institute for Forensic Medicine. The results of our investigation showed no rehospitalization owing to pulmonary oedema or coma, but one death, outside the hospital, owing to delayed pulmonary oedema. This delayed complication had an incidence of 0.6% (95% confidence interval 0-3.8%). A reintoxication could be excluded in this patient. Based on reliable report, the pulmonary oedema occurred between approximately 2 1/4 and 8 1/4 hours after intoxication. In the literature, only two cases of delayed pulmonary oedema have been reported with reliable time statements (4 and 6 h after hospitalization). We therefore conclude that surveillance for at least 8 h is essential after successful treatment to exclude delayed pulmonary oedema in patients intoxicated with heroin or heroin mixtures.

Topics: Adolescent; Adult; Benzodiazepines; Cannabis; Drug Interactions; Drug Overdose; Emergency Service, Hospital; Emergency Treatment; Ethanol; Female; Glasgow Coma Scale; Heroin; Heroin Dependence; Humans; Male; Monitoring, Physiologic; Narcotics; Prospective Studies; Survival Rate; Switzerland; Time Factors

Thirty-eight, adult, male, detoxified, Malaysian opiate addicts participated in this double-blind clinical evaluation of naltrexone. Addicts from three ethnic groups: Chinese, Malays, and Indians received a weekly regimen of naltrexone (100 mg on Days 1 and 3, and 150 mg on Day 5). Subjects were randomly assigned to receive intravenous challenge with either 25 mg heroin or placebo 12, 24, 48, and 72 h after the third naltrexone dose. Physiological and subjective parameters were measured at each challenge interval. Results indicated that naltrexone was effective in blocking the physiological and psychological effects of heroin for at least 48 and 72 h, respectively, in detoxified Malaysian opiate addicts. The efficacy of naltrexone did not differ among the three ethnic groups evaluated in this study.

Topics: Adult; Arousal; Cross-Cultural Comparison; Dose-Response Relationship, Drug; Double-Blind Method; Heroin; Heroin Dependence; Humans; Malaysia; Male; Naltrexone; Neurologic Examination; Receptors, Opioid; Substance Abuse, Intravenous

Long-term opioid consumption can induce hypoadrenalism through impairment of the hypothalamic-pituitary-adrenal axis. Results of the present study showed that, in heroin addicts, saliva cortisol concentrations varied according to the amount of recently consumed heroin and the time elapsed since the last self-administration. Hypercortisolism was observed either after abrupt withdrawal of heroin or the last dose of methadone. Post-detoxification hypercortisolism was still present on day 16 after the last opioid consumption, whereas it was not observed in abstinent addicts for a mean period of 4 months. During detoxification treatment, mean AUC8-24 cortisol in saliva of clonidine or guanfacine-treated patients was significantly higher than that in methadone-treated patients. It may be hypothesized that elevated cortisol levels may account for untoward effects of adrenergic agonist therapy which, in turn, may represent an added risk factor for relapse during detoxification. Further studies are necessary to correlate the severity of withdrawal symptoms to cortisol levels in opioid addicts detoxified with alpha 2-adrenergic agonist substitution.

Topics: Adult; Circadian Rhythm; Clonidine; Double-Blind Method; Guanfacine; Heroin; Heroin Dependence; Humans; Hydrocortisone; Male; Methadone; Substance Withdrawal Syndrome

To assess the efficacy of buprenorphine for short-term maintenance/detoxification.. A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase.. Outpatient facilities at the Addiction Research Center, Baltimore, Md.. One hundred sixty-two volunteers seeking treatment for opioid dependence.. In addition to the medication, counseling using a relapse prevention model was offered but not required.. Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence.. Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups.. Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Proportional Hazards Models

Interim methadone maintenance has been proposed as a method of providing clinically effective services to heroin addicts waiting for treatment in standard comprehensive methadone maintenance programs.. A clinic that provided initial medical evaluation, methadone medication, and AIDS education, but did not include formal drug abuse counseling or other social support services was established in New York City. A sample of 301 volunteer subjects recruited from the waiting list for treatment in the Beth Israel methadone program were randomly assigned to immediate entry into the interim clinic or a control group.. There were no differences in initial levels of illicit drug use across the experimental and control groups. One-month urinalysis follow-up data showed a significant reduction in heroin use in the experimental group (from 63% positive at intake to 29% positive) with no change in the control group (62% to 60% positive). No significant change was observed in cocaine urinalyses (approximately 70% positive for both groups at intake and follow-up). A higher percentage of the experimental group were in treatment at 16-month follow-up (72% vs 56%).. Limited services interim methadone maintenance can reduce heroin use among persons awaiting entry into comprehensive treatment and increase the percentage entering treatment.

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; New York City; Regression Analysis; Rehabilitation; Substance Abuse Treatment Centers; Substance Abuse, Intravenous

The levels of opioid physical dependence in a group of long-term heroin addicts were ascertained by measuring the severity of the opioid withdrawal syndrome before and after pharmacological challenge with either 0.4 mg naloxone or placebo. Prior to challenge, patients manifested some subjective symptoms but few objective signs of opioid withdrawal. Patients who received placebo (n = 18) showed a significant increase in the mean score on one of three rating scales used to assess opioid withdrawal. Patients who received naloxone (n = 58) showed significant increases in mean scores on all three rating scales, but this was due primarily to increases observed in a minority of patients. Sixty-one percent of patients failed to manifest clinically significant changes in subjective symptoms, and 74% of patients failed to manifest clinically significant changes in objective signs of opioid withdrawal following naloxone administration. The results suggest that a substantial subgroup of heroin addicts are able to use opioids regularly while maintaining relatively low levels of physical dependence.

Topics: Adult; Drug Tolerance; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Naloxone; Neurologic Examination; Substance Withdrawal Syndrome

We conducted a study to assess the clinical usefulness of transdermal clonidine for heroin detoxification in an outpatient drug treatment clinic. Twenty-two young otherwise healthy heroin addicts participated. Outcome was assessed on the basis of (a) hypotension and other side effects of clonidine; (b) patient retention; (c) concomitant drug use; (d) subjective symptoms of withdrawal; and (e) objective signs of withdrawal. Side effects were present but in no case necessitated discontinuation of treatment. Drop-out rates were equal to conventional treatment offered at the clinic. The availability of clonidine broadens the therapeutic options available to patients and clinicians in treating the opiate-addicted patient. Transdermal clonidine offers several advantages over the oral form: patches can be applied weekly, fewer supplemental medications are required, and patches supply an even blood level of medication. A protocol for use is recommended.

Topics: Administration, Cutaneous; Adult; Ambulatory Care; Clinical Trials as Topic; Clonidine; Female; Heroin; Heroin Dependence; Humans; Male; Prospective Studies; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Chlordiazepoxide; Chlorpromazine; Clinical Trials as Topic; Clonidine; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; India; Male; Random Allocation; Substance Withdrawal Syndrome

A total of 410 patients (342 men and 68 women) addicted to heroin for at least 38 months, with or without previous methadone treatment experience, were treated with sulpiride before the appearance of withdrawal syndrome. The drug was injected intramuscularly in a single administration at a dosage of 600 mg. Successively, sulpiride was injected intramuscularly at a dosage of 200 mg 3 times per day from days 2-21 of hospitalization, and then at a dosage of 100 and 50 mg 3 times per day (days 22-25 and 26-29, respectively). All patients showed a suppression of withdrawal signs and symptoms within 6 days of treatment, as assessed by subjective and objective scores. The effect of sulpiride was compared with that of placebo administered to a control group of 10 heroin addicts. Because prolactin has been shown to reduce the dependence of rats to heroin and the naloxone-precipitated withdrawal syndrome in morphine-addicted animals, the effects of sulpiride on heroin addiction may be related to the hyperprolactinemic action of this drug.

Topics: Adolescent; Adult; Animals; Brain; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Prolactin; Rats; Substance Withdrawal Syndrome; Sulpiride; Synaptic Transmission

Cigarette smoking increased during administration of buprenorphine, an opioid mixed agonist-antagonist, in comparison to drug-free baseline in seven heroin addicts maintained on buprenorphine for 24 days (P less than 0.01-0.001). Ascending buprenorphine doses (0.5 - 8.0 mg/day) were associated with significant increases in cigarette smoking at doses of 2.0 mg/day sc and above. Cigarette smoking during 10 days of buprenorphine maintenance at 8 mg/day was significantly higher than during the buprenorphine induction phase (P less than 0.01). Six subjects given placebo buprenorphine over 14 days showed no change in cigarette smoking. The placebo group self-administered heroin for 10 days, and cigarette smoking increased significantly during heroin use (P less than 0.001). The rate of cigarette smoking defined by intercigarette intervals was highest during the 10 days of high-dose buprenorphine maintenance or placebo plus heroin self-administration. Both groups requested significantly more cigarettes at intervals of 0-10, 11-20, and 21-30 min than during the drug-free baseline. These data confirmed previous findings that opioid agonist administration is associated with increased cigarette smoking and suggest that buprenorphine has primarily agonist effects on cigarette smoking.

Topics: Adult; Buprenorphine; Dextroamphetamine; Dose-Response Relationship, Drug; Endorphins; Ethanol; Heroin; Heroin Dependence; Humans; Male; Methadone; Morphinans; Smoking; Time Factors

A pilot study was conducted at two maintenance programs to test the effect of increasing the methadone dose of clients who continue chronic heroin use after stabilization on methadone. Program 1 subjects (Group 1) received substantial dose increases for a 14-week period; Program 2 subjects (Group 2) received no dose modifications during the same period. Results show Group 1 reported an alleviation of physical and psychological complaints but did not decrease illicit opiate use. Group 2 maintained the low level of complaints reported at baseline and, unexpectedly, decreased opiate abuse. Because the two maintenance programs differed in clinical practices and in enforcement of rules, it was concluded that clients who continue chronic heroin use need not only long-term dosage increases, but also clear, consistently applied program policies.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Methadone; Psychological Tests

Structured, psychotherapeutic counselling during 21-day heroin detoxification was evaluated by randomly assigning a group of 25 heroin addicts to a detoxification treatment regimen with mandatory counselling by a therapist and 25 to a control group who received only standard detoxification without counselling. There was no significant difference between groups in the number who successfully detoxified as measured by conversion of morphine positive urine to morphine negative urine. The counselling intervention group did, however, improve the attendance of subjects while in detoxification treatment, and significantly more patients entered long-term treatment following detoxification. Maximal use of a counselor during 21-day heroin detoxification may best be realized by directing therapy toward engaging patients in long-term care.

Topics: Adolescent; Adult; Counseling; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Psychotherapy

Ninety-six confirmed heroin addicts requesting a heroin maintenance prescription were randomly allocated to treatment with injectable heroin or oral methadone. Progress was monitored throughout the next 12 months by research workers operating independently of the clinic. Heroin can be seen as maintaining the status quo, with the majority continuing to inject heroin regularly and to supplement their maintenance prescription from other sources; it was associated with a continuing intermediate level of involvement with the drug subculture and criminal activity. Refusal to prescribe heroin while offering oral methadone constituted a more confrontational response and resulted in a higher abstinence rate, but also a greater dependence on illegal sources of drugs for these who continued to inject. Those offered oral methadone tended to polarize toward high or low categories of illegal drug use and involvement with the drug subculture, and were more likely to be arrested during the 12-month follow-up. There was no difference between the two groups in terms of employment, health, or consumption of nonopiate drugs. Refusal to prescribe heroin resulted in a significantly greater drop out from regular treatment.

Topics: Adolescent; Adult; Clinical Trials as Topic; Crime; Dose-Response Relationship, Drug; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Outcome and Process Assessment, Health Care; Random Allocation; Social Adjustment; United Kingdom

Sixty-eight heroin addicts maintained for 40 weeks on a regimen of methadyl acetate or methadone hydrochloride in a double-blind study were transferred to a uniform dose of 60 mg of methadone daily at the end of their tenure in the study. They were observed for the ensuing six weeks, during which their daily methadone doses were adjusted according to their clinical needs. Patients were observed for symptoms and signs of discomfort and for the amount of illicit drug use during this period of transition. The results indicate that patients maintained on a regimen of methadyl acetate can be readily restabilized with methadone and that sudden decrease of the methadone dose tends to result in the patient's supplementing with illicit heroin. Conversely, increasing methadone doses resulted in a corresponding reduction in illicit drug use. It is suggested that a chronic covert abstinence syndrome may exist in some patients receiving long-term methadone maintenance therapy, and that while it may contribute to their continued illicit drug use, it may have a different pathophysiologic basis and require different therapeutic considerations.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Heroin; Heroin Dependence; Humans; Male; Methadone; Methadyl Acetate; Middle Aged

1 Intravenous heroin (diamorphine) was administered to volunteers, in doses of 2.5 and 5 mg to non-dependent and doses of 1/6, 1/3 and 1/2 of their prescribed daily dose of opiates to dependent subjects, and heart and respiration rates, blood pressure, body and skin temperature and skin conductance were measured before and for 2 h after injection. 2 Heart rate fell and continued to fall after injection in both groups of subjects although the time course was different in the two groups. This was thought to be a non-specific effect of heroin. 3 Respiration rate fell after injection in both groups. The dependent group showed a faster recovery of pre-drug respiration rate. This was interpreted as being due to tolerance in the dependent group. 4 Systolic blood pressure fell only in the dependent group and diastolic blood pressure only fell after injection of the largest dose of heroin in both groups. 5 Body temperature fell after injection of heroin in a similar way in both groups while neither skin temperature nor skin conductance changed. This was interpreted as a drug-induced alteration in thermo-regulatory mechanisms. 6 Placebo had no effect on any of these measures. There were no differences between the responses of the high and low dose dependent subjects to different doses of heroin nor did prior ingestion of methadone affect any of the measures.

Topics: Blood Pressure; Body Temperature; Heart Rate; Hemodynamics; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Pupil; Respiration

In a double-blind study carried out between 1972 and 1975 in Hong Kong 100 heroin addict volunteers were initially admitted to hospital for two weeks for stabilisation on 60 mg of methadone before being assigned at random to two groups: one group received methadone (range 30--130 mg, average 97 mg/day); those in the other group had their dose of methadone reduced at the rate of 1 mg/day and were then maintained on placebo. All subjects were provided with a broad range of supportive services. After thirty-two weeks 10% of the controls were still on treatment, compared with 76% of those receiving methadone. At the end of the three-year project, only 1 of the original 50 placebo subjects still turned up for treatment (2%), whereas the retention-rate (proportion still on treatment) for methadone subjects was 56%. Subjects who had dropped out of the study and were readmitted for methadone treatment under known conditions had the same retention-rate as the original treatment group.

Topics: Adult; Aged; Ambulatory Care; Clinical Trials as Topic; Double-Blind Method; Follow-Up Studies; Heroin; Heroin Dependence; Hong Kong; Humans; Male; Methadone; Middle Aged; New York City; Patient Dropouts; Placebos; Time Factors

This paper reviews older results on EEG and behavioral effects of heroin and opiate antagonists in exaddicts, and presents new findings on the effects of naltrexone in men who have never been addicted. Ten normal volunteers were given on three separate occasions placebo, 50 mg or 100 mg of naltrexone. The average alpha frequency was significantly slower after naltrexone than after placebo. Naltrexone elicited a significant reduction of breathing rate and oral temperature. Those results indicate that naltrexone does not act as a pure narcotic antagonist in non-addicted men.

Topics: Auditory Threshold; Circadian Rhythm; Electroencephalography; Electrooculography; Heroin; Heroin Dependence; Humans; Male; Naloxone; Naltrexone; Time Factors

A multiclinic controlled trial of naltrexone in opiate-dependent persons led to these conclusions: (1) a narcotic antagonist is an acceptable treatment for a small number of patients undergoing treatment for opiate dependence; (2) the group most likely to be candidates for such treatment are those who are relatively opiate-free ("post-addicts") and well motivated to seek treatment; (3) although differences between patients treated with placebo and naltrexone were slight, both retention in treatment and opiate-free urine tests favored the naltrexone group; (4) adverse effects of relatively short-term treatment were slight, largely being symptoms and signs of precipitated abstinence in patients with residual dependence.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Heroin; Heroin Dependence; Humans; Male; Methadone; Motivation; Naloxone; Naltrexone; Patient Compliance; Placebos; Research Design; Social Adjustment

The development of cross-tolerance between methadone and heroin was studied in postaddict volunteers who had been drug-free for at least 6 weeks. Two methadone dose schedules were used; each was employed in six subjects. One schedule brought the subjects to a dose of 40 mg, while the other brought them to 80 mg of methadone a day. Subjects received injections of heroin (0.214 mg/kg) and placebo at various times before and during methadone treatment. Pupillary and subjective effects of injections were measured. Plasma levels of methadone were determined concurrently. Subjects on both treatment schedules developed an incomplete cross-tolerance to this dose of heroin. As the dose and plasma level of methadone increased with time, the cross-tolerance to all heroin effects increased. Plasma levels did not affect the development of cross-tolerance independently of methadone dose. The most important contribution to the cross-tolerance to pupillary effects was made by the duration of methadone treatment. Furthermore, the cross-tolerance to the subjective effects of heroin developed earlier than that to the pupil effect.

Topics: Adult; Dose-Response Relationship, Drug; Drug Tolerance; Heroin; Heroin Dependence; Humans; Male; Methadone; Pupil

Patients in a methadone maintenance clinic were randomly assigned to two groups: one to have urine tests on-site (by the EMIT system) with immediate feedback of results to patients and staff; the other to have urine specimens sent away to an offsite laboratory for testing by thin-layer chromatography. Although other advantages might justify the adoption of on-site testing in methadone programs, the method appeared to have little or no therapeutic advantage over customary off-site testing. There were negligibly small differences between the groups with respect to illicit drug use.

Topics: Adult; Chromatography, Thin Layer; Consumer Behavior; Feedback; Female; Heroin; Heroin Dependence; Humans; Immunoassay; Male; Methadone; Patient Compliance; Time Factors

Topics: Analgesics; Analgesics, Opioid; Clinical Trials as Topic; Drug Administration Schedule; Drug Evaluation; Drug Tolerance; Heroin; Heroin Dependence; Humans; Kinetics; Methadone; Methadyl Acetate; Morphine; Morphine Dependence; Patient Dropouts; Substance Withdrawal Syndrome; Time Factors

Among the increasing number of recent reports of the use of beta-adrenergic blocking drugs for a variety of psychiatric disorders is a series concluding that propranolol hydrochloride is efficacious in the treatment of opiate dependence. These reports were based on clinical observations of outpatient addicts in an uncontrolled situation. In order to validate these findings, we carried out a series of controlled, double-blind studies with hospitalized volunteers. The results of our studies do not confirm the previous reports. Propranolol neither relieved nor precipitated opiate withdrawal in subjects dependent either on dihydromorphinone hydrochloride or on heroin. It did not effectively block heroin-induced euphoria in dependent or nondependent subjects. In addition, there was no effect on the pattern of self-administration in opiate-dependent subjects, whether they were maintained on propranolol or placebo.

Topics: Adult; Clinical Trials as Topic; Heroin; Heroin Dependence; Humans; Hydromorphone; Male; Propranolol; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Aftercare; Age Factors; Clinical Trials as Topic; Conditioning, Psychological; Drug Administration Schedule; Extinction, Psychological; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Research Design; Self Administration; Time Factors

Topics: Clinical Trials as Topic; Conditioning, Psychological; Cyclazocine; Drug Evaluation; Euphoria; Heroin; Heroin Dependence; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Research; Research Support as Topic; United States; United States Substance Abuse and Mental Health Services Administration

This is a presentation of the results of pilot and controlled research on the effectiveness of the contingent (upon narcotic drug use) administration of 500-2,000 mg daily, of the narcotic antagonist, naloxone (N-allylnoroxymorphone), to paroled narcotic addicts enrolled in a urine monitoring program conducted in a metropolitan-based outpatient clinic. Criteria of effectiveness, which include clinic attendance, the extent of narcotic drug usage, and final disposition at the end of a 6-month treatment period, are viewed in relation to already established baseline results with a sample of patients processed through the same clinic over a 5-year period prior to the introduction of naloxone treatment. Although results of the pilot study are encouraging, indicating longer patient involvement and less reinstitutionalization than baseline values, the results of the controlled evaluation reveal no benefit from contingently administered naloxone beyond placebo reactivity, which appears to be substantial in the contingent approach. The results are discussed in terms of given sample characteristics, and suggestions are offered regarding the development of new narcotic antagonist treatment approaches.

Topics: Adolescent; Adult; Clinical Trials as Topic; Drug Evaluation; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Maryland; Middle Aged; Naloxone; Pilot Projects; Placebos

Topics: Administration, Oral; Affective Symptoms; Clinical Trials as Topic; Cyclazocine; Dose-Response Relationship, Drug; Drug Evaluation; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Placebos; Time Factors

Topics: Acoustic Stimulation; Adult; Alpha Rhythm; Attention; Auditory Perception; Electroencephalography; Emotions; Heart Rate; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Placebos; Pupil; Reaction Time; Respiration; Time Factors

Topics: Adult; Clinical Trials as Topic; Heroin; Heroin Dependence; Humans; Placebos; Propranolol; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis.. Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse.. Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical-striatal-thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse.. MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.

Topics: Brain; Heroin; Heroin Dependence; Humans; Male; Methadone; Opiate Substitution Treatment; Recurrence

The objective was to evaluate outcomes in a heroin-dependent population 35 years after first enrolment in methadone maintenance treatment (MMT).  An ad hoc protocol was used to assess drug misuse, treatment, and drug-related morbidity in the survivor sample. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated.  A total of 214 heroin-dependent patients entered MMT between 1982 and 1984 in the Asturias Public Health Service. Information was received on 195 subjects, of whom 146 were deceased.  Men accounted for 77.5% of the study cohort. Over the 35-year follow-up period, the SMR was 11.75 (95% CI = 9.95 - 13.77). In the survivor sample, 5.7% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 38.77% and hepatitis B/C in 73.46%. No differences were found between sexes in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 35-year follow-up compared with 5.26% of males. In conclusion, our study confirms the high long-term mortality rate of heroin addicts, even after enrollment in MMT.. El objetivo fue evaluar el estado de una población dependiente a la heroína 35 años después de su primera inscripción en un tratamiento de mantenimiento con metadona (TMM). Se utilizó un protocolo ad hoc para evaluar morbilidad, consumo y tratamiento de la adicción en la muestra de supervivientes. Se calculó la razón de mortalidad estandarizada (RME) con un intervalo de confianza (IC) del 95%. Un total de 214 pacientes ingresaron en TMM entre 1982 y 1984 en el Servicio de Salud Pública de Asturias. Se recibió información sobre 195 sujetos, de los cuales 146 habían fallecido. Los hombres representaron el 77,5% de la cohorte del estudio. Durante el período de seguimiento de 35 años, la RME fue de 11,75 (IC 95% = 9,95 – 13,77). En la muestra de supervivientes, el 5,7% todavía estaba inscrito en TMM; el virus de inmunodeficiencia humana (VIH) se diagnosticó en un 38,77% y la hepatitis B/C en un 73,46%; el consumo actual de heroína se informó en un 4,1%. No hubo diferencias de género en la mortalidad o la condición de VIH y hepatitis B/C. Ninguna de las mujeres consumía heroína en el seguimiento de 35 años en comparación con el 5,26% de los hombres. En conclusión, nuestro estudio confirma la alta tasa de mortalidad a largo plazo, incluso después de la inscripción en TMM.

Topics: Female; Follow-Up Studies; Hepatitis B; Hepatitis C; Heroin; Heroin Dependence; HIV Seropositivity; Humans; Male; Methadone; Opiate Substitution Treatment; Spain

Craving and impulsivity are addiction components which explain why heroin-dependant individuals (HDI), continue using heroin despite not wanting to do so. Opioid maintenance treatment (OMT), such as slow-release oral morphine (SROM), is the most effective treatment for opioid dependence. However, the impact of SROM on craving and impulsivity remains unclear. In this observational study, 23 HDI receiving SROM, their usual OMT, took part in the experiment. Each of the participants filled in the perceived level of craving with a visual analog scale. Their impulsivity was assessed via three laboratory tasks, the stop-signal reaction time, the Balloon Analogue Risk Task and delay discounting. Each evaluation was performed before and after SROM administration. Craving was significantly reduced after administration of SROM (difference 2.83; P  = 0.0010), whereas there were no significant differences in performance in the three laboratory tasks. In the long term, we observed an improvement on delay discounting correlated with the duration and dosage of SROM. The acute impact of SROM appears to significantly reduce craving, without impacting impulsivity. Observation of the correlation between delay discounting and the duration and dosage of OMT is of great interest and should be studied further.

Topics: Heroin; Heroin Dependence; Humans; Morphine

To date, few studies have investigated the toxicological effects of the combined use of amphetamine and heroin in the heart. Hence, the aim of this study was to identify indicators for clinical evaluation and prevention of cardiac injury induced by the combined use of amphetamine and heroin. Four different groups were analyzed: (1) normal group (

Topics: Adult; Aged; Amphetamine; Biomarkers; Heart Diseases; Heart Injuries; Heroin; Heroin Dependence; Humans; Insulin-Like Growth Factor I; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Tumor Necrosis Factor-alpha

Heroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM.. This is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated.. Participants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported.. After four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM.

Topics: Analgesics, Opioid; Feasibility Studies; Heroin; Heroin Dependence; Humans; Opioid-Related Disorders; Switzerland

The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based

Topics: Analgesics, Opioid; Animals; Female; Heroin; Heroin Dependence; Male; Nucleus Accumbens; Pain; Rats; Rats, Transgenic; Receptors, Opioid; Receptors, Opioid, mu

We and others have observed reduced volumes of brain regions, including the nucleus accumbens, globus pallidus, hypothalamus, and habenula in opioid addiction. Notably, the insular cortex has been under increasing study in addiction, and a smaller anterior insula has been found in alcohol-addicted cases. Here, we have investigated whether similar effects occur in heroin addicts compared to healthy controls. Volumes of the anterior and posterior insula in heroin addicts (n = 14) and controls (n = 13) were assessed by morphometry of Nissl-myelin-stained serial whole-brain coronal sections. The mean relative volume of the anterior insular cortex was smaller than in non-addicted controls (3010 ± 614 *10

Topics: Brain; Cerebral Cortex; Heroin; Heroin Dependence; Humans; Insular Cortex; Magnetic Resonance Imaging; Male; Nucleus Accumbens

The effects of transcranial magnetic stimulation in treating substance use disorders are gaining attention; however, most existing studies used subjective measures to examine the treatment effects. Objective electroencephalography (EEG)-based microstate analysis is important for measuring the efficacy of transcranial magnetic stimulation in patients with heroin addiction. We investigated dynamic brain activity changes in individuals with heroin addiction after transcranial magnetic stimulation using microstate indicators. Thirty-two patients received intermittent theta-burst stimulation (iTBS) over the left dorsolateral prefrontal cortex. Resting-state EEG data were collected pre-intervention and 10 days post-intervention. The feature values of the significantly different microstate classes were computed using a K-means clustering algorithm. Four EEG microstate classes (A-D) were noted. There were significant increases in the duration, occurrence, and contribution of microstate class A after the iTBS intervention. K-means classification accuracy reached 81.5%. The EEG microstate is an effective improvement indicator in patients with heroin addiction treated with iTBS. Microstates were examined using machine learning; this method effectively classified the pre- and post-intervention cohorts among patients with heroin addiction and healthy individuals. Using EEG microstate to measure heroin addiction and further exploring the effect of iTBS in patients with heroin addiction merit clinical investigation.

Topics: Attention; Electroencephalography; Heroin; Heroin Dependence; Humans; Transcranial Magnetic Stimulation

Detecting undisclosed methamphetamine and heroin abuse is a challenge for life underwriters and medical directors. A common clinical assumption is that if substance abusers experience liver damage, it will be indicated by elevated serum transaminases. The following case suggests that assumption may not be true for heavy substance abusers who consume no or minimal alcohol. This report describes a 44-year-old male with long-term use of inhaled combined methamphetamine and heroin ("speedballs") and minimal alcohol use, whose transaminases remained normal while episodes of acute liver failure and transient hepatic encephalopathy from hyperammonemia were observed. In this case, a fatal motor vehicle accident occurred following the sudden onset of hepatic encephalopathy hours after consuming a "speedball." Normal transaminases may not be proof of a normal healthy liver among methamphetamine and heroin abusers.

Topics: Adult; Hepatic Encephalopathy; Heroin; Heroin Dependence; Humans; Male; Methamphetamine

Attention-deficit/hyperactivity disorder (ADHD) is a childhood neurodevelopmental disorder that can persist into adulthood. The co-occurrence of ADHD and substance use disorders is very frequent and has received considerable attention in recent clinical/scientific investigations. However, few studies have investigated the prevalence of ADHD in heroin addicts. This study aimed to investigate the prevalence of attention-deficit/hyperactivity disorder (ADHD) in a sample of heroin addicts treated with opioid agonists and to report this clinical experience in a public service for addiction. Outpatients over 18 years old and being treated with opioid agonists for heroin addiction were enrolled. Each patient took part in a psychiatric examination and completed an ASRS (Adult ADHD Self-Report Scale) self-assessment. Subjects with positive results were called in for another psychiatric visit, and the Brown ADD scale was used as a second-level test for ADHD; furthermore, the Mini International Neuropsychiatric Interview (MINI) and Hypomania/Mania Checklist (HCL-32) were used for differential diagnoses and to assess comorbidities. In total, 111 patients were enrolled. All were followed up by the psychiatrist, who is also the author of this report and the person who formulated the diagnoses. The prevalence of ADHD in this sample was 18%. Among the 20 patients diagnosed with ADHD, 5 (25%) were female and 15 (75%) were male. The most frequent psychiatric comorbidity was major depression, found in 11 patients (55%), of which 4 presented with hypomania (bipolar disorder). In this sample, making diagnoses was very difficult. Frequently, multiple comorbidities further complicated these cases. In conclusion, the results of this study are consistent with the literature: There seems to be a significant prevalence of ADHD even among heroin addicts, and often, the diagnosis is difficult to make. We also do not know the exact effect of opioid agonist therapy on ADHD symptoms. Hypotheses have been put forward, but studies are needed.

Topics: Adolescent; Adult; Analgesics, Opioid; Attention Deficit Disorder with Hyperactivity; Child; Comorbidity; Female; Heroin; Heroin Dependence; Humans; Male; Mania; Prevalence

Treatment strategies that aim to promote abstinence to heroin use and reduce vulnerability to drug-use resumption are limited in sustainability and long-term efficacy. We have previously shown that environmental enrichment (EE), when implemented after drug self-administration, reduces drug-seeking and promotes abstinence to cocaine and heroin in male rats. Here, we tested the effects of EE on abstinence in an animal conflict model in males and females, and after periods where incubation of craving may occur.. Male and female rats were trained to self-administer heroin followed by 3 or 21 days of a no-event-interval (NEI). Following NEI, rats were permanently moved to environmental enrichment (EE) or new standard (nEE) housing 3 days prior to resuming self-administration in the presence of an electric barrier adjacent to the drug access lever. Electric barrier current was increased daily until rats ceased self-administration.. We found that 21 days of NEI led to significantly greater heroin self-administration and a trend toward shorter latencies to emit the first active lever press in the first abstinence session compared to 3 days of NEI. EE, when compared to nEE, led to longer latencies in the first abstinence session. Also, EE groups of both sexes and in both NEIs achieved abstinence criteria in significantly fewer numbers of sessions.. EE facilitates abstinence in males and females and after periods where incubation of craving may occur. This suggests that EE may benefit individuals attempting to abstain from heroin use and may aid in the development of long term treatment strategies.

Topics: Animals; Cocaine; Craving; Cues; Female; Heroin; Heroin Dependence; Male; Rats; Rats, Sprague-Dawley; Self Administration

Injection and inhalational heroin use are associated with different levels of brain exposure to heroin and its metabolites and differences in the severity of dependence, which might lead to differential impacts on neuropsychological functions. We examined the difference and the magnitude of difference in the neuropsychological functions between inhalational and injection heroin-dependent subjects and also compared them with healthy controls.. The study sample comprised three groups: 73 subjects with injection heroin dependence, 74 with inhalational heroin dependence, and 75 healthy controls (HC). We excluded patients with HIV, head injury, epilepsy, and severe mental illness. Neuropsychological assessments were done by Standard Progressive Matrices, Wisconsin Card Sorting Test (WCST), Iowa Gambling Task, Trail-Making Tests A and B (TMT), and Verbal and Visual Memory 1 and 2 Backtests (NBT). We estimated independent effects of the groups on various neuropsychological test parameters, adjusted for age and duration of dependence.. In the WCST, the inhalational heroin-dependent group took more trials to complete the first category and had higher scores in the failure to maintain set than controls. The intravenous group had higher total errors than controls in verbal working memory tests and Visual Working Memory 2 Backtest. This group scored higher commission errors in the Verbal 2 Backtest than the controls. The two groups of heroin users differed in failure to maintain set and Verbal Working Memory 2 Backtests. The effect sizes of the group differences were modest.. Either route of heroin use is associated with cognitive impairments; inhalational and injection use involve different cognitive domains.

Topics: Heroin; Heroin Dependence; Humans; Memory, Short-Term; Neuropsychological Tests; Wisconsin Card Sorting Test

To understand the geopolitics of the supply of fentanyl and heroin.. In our practice, the percent of fentanyl positive drug tests increased from years 2016 to 2022, but heroin positive drug tests decreased by 80% in the same period.. Fentanyl has replaced heroin as a street drug for opioid dependent drug users.

Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Heroin Dependence; Humans

In the present study, performed on a sample of Heroin Use Disorder (HUD) patients undergoing Opioid Agonist Treatment (OAT), we attempted to explore the relationships between stress sensitivity and heroin addiction-related clinical aspects. HUD patients' stress sensitivity was evaluated with the Heroin/PTSD-Spectrum questionnaire (H/PSTD-S). The Drug Addiction History Questionnaire (DAH-Q), the Symptomatological Check List-90 (SCL-90), and The Behavioural Covariate of Heroin Craving inventory (CRAV-HERO) were all used, as were the Deltito Subjective Wellness Scale (D-SWS), a self-report scale evaluating subjective well-being; the Cocaine Problem Severity Index (CPSI), a questionnaire determining the extent of a cocaine problem; and the Marijuana Craving Questionnaire (MC-Q), an instrument assessing craving for cannabinoids. We checked correlations between stress sensitivity and the extent of HUD clinical features and compared patients with and without problematic stress sensitivity. H/PTSD-S was positively correlated with patients' income, altered mental status, legal problems, the lifetime different treatments index, the current treatment load index, and all SCL-90 indexes and factors. Regarding subjective well-being, stress sensitivity negatively correlated with the contrast best week (last five years) index. Patients with high-stress sensitivity were females with a low income. They exhibited a more severe mental status at treatment entry, greater difficulty in working adaptation, and legal problems during treatment. Additionally, these patients showed a higher level of psychopathology, more impairment in well-being, and more risky behaviours during treatment. Stress sensitivity, as H/PTSD-S, must be considered an outcome of HUD. HUD's addiction history and clinical features are significant risk factors for H/PTSD-S. Therefore, social and behavioural impairment in HUD patients could be considered the clinical expression of the H/PTSD spectrum. In summary, the long-term outcome of HUD is not represented by drug-taking behaviours. Rather, the inability to cope with the contingent environmental conditions is the key feature of such a disorder. H/PTSD-S, therefore, should be seen as a syndrome caused by an acquired inability (increased salience) concerning regular (daily) life events.

Topics: Analgesics, Opioid; Cocaine; Female; Heroin; Heroin Dependence; Humans; Male; Opiate Substitution Treatment

Reverse takotsubo cardiomyopathy is triggered by emotional or physical stress and has a presentation similar to that of acute coronary syndrome. A 39-year-old woman with a history of heroin use disorder presented with intractable nausea, vomiting, and diarrhea. She was diagnosed with heroin withdrawal and started on buprenorphine-naloxone. On day 2 of her hospitalization, she developed chest heaviness and had an elevated troponin I level of 3.2 ng/mL (reference range, 0.015-0.045 ng/mL); electrocardiography showed new T-wave inversions in the anterior and inferior leads. Emergent coronary angiography showed patent coronary arteries, and left ventriculography showed basal hypokinesis and apical hyperkinesis, consistent with reverse takotsubo cardiomyopathy secondary to heroin withdrawal. She was started on antihypertensive agents, and her buprenorphine-naloxone dose was increased. At her 3-month follow-up visit, she reported no symptoms consistent with angina or heart failure. This appears to be the first report of heroin withdrawal causing reverse takotsubo cardiomyopathy. Awareness of this association can lead to earlier recognition and treatment of reverse takotsubo cardiomyopathy.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Electrocardiography; Female; Heroin; Heroin Dependence; Humans; Takotsubo Cardiomyopathy

Heroin-Assisted Treatment (HAT) is well evidenced internationally to improve health and social outcomes for people dependent on opioids who have not been helped by traditional treatment options. Despite this evidence base, England has been slow to implement HAT. The first service outside of a trial setting opened in 2019, providing twice-daily supervised injections of medical-grade heroin (diamorphine) to a select sample of high-risk heroin users in Middlesbrough. This paper explores their experiences, including the negotiation of the strict regularly controls required of a novel intervention in the UK context.. We conducted in-depth interviews with service providers and users of the Middlesbrough HAT service between September and November 2021. Data from each group were thematically analysed and reported separately. This paper details the experiences of the twelve heroin dependent men and women accessing HAT.. Participants' accounts of HAT treatment evidenced a tension between the regulatory constraints and uncertainty of treatment provision, and the positive outcomes experienced through supportive service provision and an injectable treatment option. Limited confidence was held in treatment efficacy, longevity of funding, and personal capacity for treatment success. This was counteracted by a strong motivation to cease engagement with the illicit drug market. While attendance requirements placed restrictions on daily activities, participants also experienced benefits from strong, supportive bonds built with the service providers through their continued engagement.. The Middlesbrough HAT programme provided benefits to a high-risk population of opioid dependent people who were unable or disinclined to participate in conventional opioid substitution treatments. The findings in this paper highlight the potential for service modifications to further enhance engagement. The closure of this programme in 2022 prohibits this opportunity for the Middlesbrough community, but holds potential to inform advocacy and innovation for future HAT interventions in England.

Topics: Analgesics, Opioid; England; Female; Heroin; Heroin Dependence; Humans; Male; Opiate Substitution Treatment

Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats.. Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain.. Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA).. The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.

Topics: Animals; Cholinergic Agents; Conditioning, Operant; Cues; Donepezil; Extinction, Psychological; Heroin; Heroin Dependence; Nootropic Agents; Rats; Rats, Sprague-Dawley; Receptors, Dopamine

Topics: Atropa belladonna; COVID-19; Heroin; Heroin Dependence; Humans; Ivermectin; Substance Withdrawal Syndrome

Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose death rates since at least 2013 and rising co-use of methamphetamine with opioids has played a greater role in deaths over the last 5 years.. This study used rapid ethnography to examine methods and motivations behind opioids and methamphetamine co-use from the viewpoint of their consumers. Participants (n = 30) were people who injected heroin/fentanyl also using methamphetamine who participated in semi-structured interviews.. We found multiple methods of co-using opioids and methamphetamine, whether alternately or simultaneously and in varying order. Most prioritized opioids, with motives for using methamphetamine forming three thematic categories: 'intrinsic use', encompassing both inherent pleasure of combined use greater than using both drugs separately or for self-medication of particular conditions; 'opioid assisting use' in which methamphetamine helped people manage their existing heroin/fentanyl use; and 'reluctant or indifferent use' for social participation, reflecting methamphetamine's low cost and easy availability.. Methamphetamine serves multiple functions among people using opioids in WV. Beliefs persist that methamphetamine can play a role in preventing and reversing opioid overdose, including some arguments for sequential use being protective of overdose. 'Reluctant' uptake attests to methamphetamine's social use and the influence of supply. The impact on overdose risk of the many varied co-use patterns needs further investigation.

Topics: Adult; Female; Fentanyl; Health Knowledge, Attitudes, Practice; Heroin; Heroin Dependence; Humans; Interviews as Topic; Male; Methamphetamine; Motivation; Pleasure; Self Medication; Social Interaction; West Virginia

In recent years, fatal and non-fatal heroin-related overdoses have increased in northeastern Italy, and the change in potency of heroin available at street level has been identified as a prominent factor associated with acute toxicity. Two very different products, high-potency and low-potency heroin were becoming available on the street, and no clear morphological characteristics could be used to easily distinguish them. A theoretical model for predicting heroin potency from rapid analysis of cigarette filters was developed as part of an overdose prevention project. The model was derived from the analysis of real heroin samples and exploits the common presence of caffeine in heroin as an adulterant. It was tested on laboratory prepared filters, real filters used to prepare heroin injections, and other paraphernalia. The model showed strong predictive ability and was used to implement a rapid alert system to inform drug users and healthcare institutions about the potency of heroin or other psychoactive substances circulating in the area. Cigarette filters were used as standard material, but other paraphernalia were successfully tested. The developed model is a dynamic tool whose parameters can be updated according to the market characteristics, so it can be useful for laboratories involved in drug analysis and similar prevention programs.

Topics: Drug Overdose; Drug Users; Heroin; Heroin Dependence; Humans; Narcotics

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (

Topics: Brain; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Methadone

Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP-1 analogue, liraglutide (LIR), in reducing heroin addiction-like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self-administration, prevents escalation of heroin self-administration and reduces drug-induced reinstatement of heroin-seeking behaviour in rats. A 1-h pretreatment time, however, was too short to reduce cue-induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR-paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin-naïve or heroin-experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain.

Topics: Animals; Cues; Glucagon-Like Peptide-1 Receptor; Heroin; Heroin Dependence; Liraglutide; Rats; Self Administration

Low-income African Americans residing in impoverished neighborhoods confront myriad barriers to adhering to antihypertensive regimens. Substance use may thwart medication adherence and lifestyle modification efforts, which has implications for excess cardiovascular disease mortality. The Inner-City Hypertension and Body Organ Damage (ICHABOD) Study was a longitudinal cohort study that evaluated causes of mortality among African Americans who lived in urban areas, had severe, poorly controlled hypertension, and were admitted to a local hospital between 1999-2001 and 2002-2004. The authors employed Cox proportional hazards models to assess mortality associated with illicit substance use, including use of heroin and cocaine, as well as by use of tobacco and alcohol. Among192 participants with poorly controlled hypertension, 30% were active illicit substance users (specifically, 22.7% heroin users, 19.8% were cocaine users, and 30.7% were both cocaine and heroin users). The mean age among substance non-users was 52.3 years versus 48.7 years among those reporting current use. Mortality over 7.6 years of follow-up was 52.5% among substance users and 33.8% among nonusers (p-value, 0.01). After adjusting for potential confounders, the hazard ratio (HR) for cocaine use was 2.52 (95% confidence interval (CI) 1.38-4.59), while the HR for heroin use was 2.47 (95% CI 1.42-4.28) and the HR for both was 2.75 (95% CI 1.60-4.73). Substance use was associated with increased mortality among urban black Americans with poorly controlled hypertension. These data suggest the need for targeted interventions to support African Americans who have poorly controlled hypertension and use illicit substances, as a means of reducing excess mortality.

Topics: Black or African American; Cocaine; Heroin; Heroin Dependence; Humans; Hypertension; Longitudinal Studies; Middle Aged; Mortality, Premature; Prospective Studies

Methadone maintenance therapy (MMT) is a well-established and effective treatment for heroin use disorders. Whether frontal lobe function and demoralization serve as suitable prognostic and outcome assessment factors remains unknown. A quasi-experimental study was conducted with a single-group repeated-measures design at a medical center and mental hospital in Taiwan. We enrolled 70 participants (39 completed treatments and 31 dropped out). Frontal lobe function, demoralization, depression, and craving at three time points were analyzed. There were differences between patients who completed the treatment (n = 39) and those who did not (n = 31). Thirty-nine patients completed the treatment (average age, 45.5 years; 89.7% men; average duration of heroin use, 27.21 years; MMT, 38.18 mg/day). Post-MMT (6 months), frontal lobe function, demoralization, depression, and craving significantly improved. Dropouts had higher frontal lobe function, lower demoralization, higher craving, younger age, and earlier onset age than patients who completed the pretest treatment. Clinicians should be aware of the severity of demoralization. Clinicians may select suitable patients for MMT by assessing frontal lobe function, demoralization, craving, age, and onset age. A 6-month course of MMT improved demoralization, frontal lobe function, depression, and addiction. Six months of treatment was more effective than 3 months. Suitable patient identification and continuous treatment are important in MMT.

Topics: Craving; Demoralization; Depression; Female; Frontal Lobe; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Prognosis

The punishment-imposed abstinence procedure models the self-imposed abstinence that humans initiate due to the adverse consequences associated with drug-taking. This model has been implemented in experiments using different types of substances of abuse such as methamphetamine, cocaine, and alcohol. However, punishment-induced abstinence in heroin-trained animals has not been demonstrated. Furthermore, acute stress is a key trigger for relapse in humans and animal models. It was previously demonstrated that acute food deprivation robustly induced reinstatement of extinguished cocaine and heroin seeking. The procedure described here can be used to assess the effects of acute stress exposure on heroin seeking after punishment-imposed abstinence. A total of 8 rats were implanted with chronic intravenous (i.v.) catheters and trained to self-administer heroin (0.1 mg/kg/infusion) for 18 days under a seek-take chained schedule. Completing the seek link gave access to the take lever, which was paired with a heroin infusion. The seek lever was programmed with a variable interval 60 schedule of reinforcement (VI60), and the take lever was programmed with a fixed-ratio 1 reinforcement schedule (FR1). Following self-administration training, a mild foot shock was delivered on 30% of the completed seek links instead of the extension of the take lever. Footshock intensity was increased by 0.1 mA per daily session from 0.2 mA to 1.0 mA. Heroin-seeking tests were performed after 24 h of food deprivation (FD) or sated conditions. Rats under acute food deprivation condition robustly increased heroin seeking after punishment-imposed abstinence.

Topics: Animals; Cocaine; Extinction, Psychological; Heroin; Heroin Dependence; Punishment; Rats; Recurrence; Self Administration

Traditionally, opioid-related disease burden was primarily due to heroin use. However, increases in extra-medical (or non-medicinal use of prescription opioids; NMPOs) use has precipitated the current overdose epidemic in North America. We aim to examine the state-level prevalence of heroin and NMPO dependence and their associations with opioid-related mortality and state-level socio-demographic profiles. Data were pooled from the 2005-2014 National Survey on Drug Use and Health (NSDUH). We examine opioid-related mortality from CDC WONDER (Cause of Death database) by the past year prevalence of DSM-IV heroin and NMPO dependence, by age and sex, and their associations with state-level socio-demographic characteristics from census data. State-level rates of heroin dependence were associated with opioid-related death rates in young and mid-aged adults, while rates of NMPO dependence were associated with opioid-related death rates across all ages. The prevalence of heroin dependence was positively associated with state-level GDP/capita and urbanity. State-level NMPO dependence prevalence was associated with higher unemployment, lower GDP/capita, and a lower high-school completion rate. The prevalence of heroin and NMPO dependence are associated with a broad range of geographical and socio-demographic groups. Taking a wider view of populations affected by the opioid epidemic, inclusive interventions for all are needed to reduce opioid-related disease burden.

Topics: Adult; Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Middle Aged; Opioid-Related Disorders; Prevalence; United States

Opioid addiction is a worldwide problem accentuated in the USA and European countries by the COVID-19 pandemic. The nucleus accumbens (NAc) plays an outstanding neurobiological role in opioid addiction as a part of the striatum and key component of brain reward system. The striatal GABAergic medium spiny projection neurons (MSNs) are the main neuronal type in the NAc where addiction-specific synaptic plasticity occurs. The activity of ribosomal DNA (rDNA) transcription is crucial for neural plasticity and molecular studies suggest its increase in the NAc of heroin addicts. Silver-stained argyrophilic nucleolar organizer region (AgNOR) areas visualised in neuronal nuclei in paraffin-embedded brain sections are reliable morphological estimators of rDNA transcription and thus surrogate markers for the activity of brain regions. Our study revealed increased AgNOR areas in MSNs of the left NAc in 11 heroin addicts versus 11 healthy controls from the Magdeburg Brain Bank (U-test P = 0.007). No differences were observed in another investigated part of the striatum, namely the head of caudate nucleus, which is located closely to the NAc. The results were not confounded by significant differences in the age, brain volume and time of formalin fixation existing between compared groups. Our findings suggest an increased NAc activity in heroin addicts, which is consistent with human and animal experimental data.

Topics: Animals; COVID-19; DNA, Ribosomal; Heroin; Heroin Dependence; Humans; Male; Nucleus Accumbens; Pandemics

Abuse of heroin vapour inhalation known as "chasing the dragon" is associated with toxic spongiform leukoencephalopathy. However, similar clinical and imaging findings may occur also after intravenous heroin abuse. We report on a 32-year-old male suffering from extensive toxic spongiform leukoencephalopathy after intravenous heroin abuse resulting in acute impairment of consciousness and a global state of confusion. MRI disclosed broad and nearly symmetrical diffusion restriction of the supratentorial white matter indicating cytotoxic oedema. In an emergency setting, differential diagnosis of acute impairment of consciousness and broad symmetrical white matter lesions in neuroimaging should also include toxic leukoencephalopathy due to intravenous heroin application.. Der als „Chasing the Dragon“ beschriebene Heroinmissbrauch durch Inhalation kann eine toxische spongiforme Leukoenzephalopathie verursachen. Wir berichten über einen 32-jährigen Mann, bei dem auch nach intravenösem Heroinmissbrauch eine toxische spongiforme Leukoenzephalopathie auftrat, die zu einer akuten Bewusstseinsstörung und einem globalen Verwirrungszustand führte. Kernspintomographisch zeigte sich eine ausgedehnte und nahezu symmetrische Diffusionsrestriktion der supratentoriellen weißen Substanz als Ausdruck eines zytotoxischen Ödems. In einer Notfallsituation sollte die Differentialdiagnose einer akuten Bewusstseinsstörung mit Nachweis symmetrischer zytotoxischer Läsionen der weißen Substanz im MRT auch eine toxische Leukoenzephalopathie aufgrund intravenöser Heroinverabreichung mit einschließen.

Topics: Adult; Consciousness; Diagnosis, Differential; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male

Traditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset ("rush") but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts.. A 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff.. Nasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.

Topics: Administration, Intranasal; Adult; Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Morphine

This qualitative study aimed to explore how the development of tolerance to both the psychoactive and respiratory depressant effects of heroin on re-exposure are experienced by people who use heroin.. Semi-structured one-to-one interviews were conducted with 20 adults who currently or previously used heroin (for at least 6 months), with any type of administration (injected, smoked) and experience of abstinence (at least 2 weeks) and relapse. Topic guides explored the participants understanding of tolerance, their experience of developing tolerance to heroin and of tolerance following relapse. Interviews were audio-recorded and transcribed. Thematic analysis was used to generate salient themes.. The analysis produced three broad themes: lay understanding of tolerance; tolerating tolerance; and rapid tolerance development following relapse. Tolerance was defined as the body adapting to regular drug use, so that the drug no longer produced the same level of effect. Tolerance was experienced as interacting and co-developing with physical dependence and the symptoms of withdrawal. Indeed, several participants did not differentiate between tolerance and dependence. Most participants did not notice tolerance to respiratory depression. Tolerance levels fluctuated-increasing over periods of regular use and reducing when abstinent. Using more drug was the most common response to increasing tolerance to the desired effects. On re-use following abstinence, tolerance was experienced as developing more quickly in the most recent relapse compared to the first. Tolerance was also perceived to return more quickly with each abstinence-relapse cycle.. Qualitative accounts of tolerance report that tolerance returns more quickly with each relapse episode. By elucidating the mechanism(s) involved and potentially discovering how they could be switched on prior to relapse occurring we might be able to develop a beneficial harm reduction treatment for people in abstinence that would protect against overdose occurring on subsequent relapse.

Topics: Adult; Analgesics, Opioid; Drug Tolerance; Heroin; Heroin Dependence; Humans; Recurrence

Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport at different stages of heroin addiction. Rat models of heroin addiction (HA) and prolonged heroin addiction (PHA) were established by injecting rats with heroin at different stages. Heroin-induced learning and memory deficits were evaluated in the Morris water maze (MWM), and MEMRI was used to dynamically evaluate axonal transport in the olfactory pathway. The expression of proteins related to axonal structure and function was also assessed by Western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes, and protein levels of neurofilament heavy chain (NF-H) were analyzed by immunofluorescence staining. HA rats, especially PHA rats, exhibited worse spatial learning and memory than control rats. Compared with HA rats and control rats, PHA rats exhibited significantly longer escape latencies, significantly fewer platform-location crossings, and significantly more time in the target quadrant during the MWM test. Mn

Topics: Animals; Axonal Transport; Brain; Heroin; Heroin Dependence; Kinesins; Magnetic Resonance Imaging; Rats

Methadone maintenance treatment (MMT) is considered as an effective and mainstream therapy for heroin dependence. However, whether long-term MMT would improve the coupling among the three core large-scale brain networks (salience, default mode, and executive control) and its relationship with the craving for heroin is unknown.. Forty-four male heroin-dependent individuals during long-term MMT, 27 male heroin-dependent individuals after short-term detoxification/abstinence (SA), and 26 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging. We analyzed the difference in coupling among the salience, default mode, and executive control networks among the three groups and examined how the coupling among these large-scale networks was associated with craving before and after drug-cue exposure.. Compared with the SA group, the MMT group showed lower craving before and after cue exposure and stronger connectivity between the dorsal anterior cingulate cortex (a key node of the salience network) and key regions of the bilateral executive control network, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and dorsomedial prefrontal cortex. Among the heroin-dependent individuals, the functional connectivity was negatively correlated with the craving before and after heroin-cue exposure.. Our findings suggest that long-term MMT could increase the coupling between the salience and bilateral executive control networks and decrease craving for heroin. These findings contribute to the understanding of the neural mechanism of MMT, from the perspective of large-scale brain networks.

Topics: Brain; Brain Mapping; Cues; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Methadone

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Topics: Antibodies; Heroin; Heroin Dependence; Humans; Morphine Derivatives

Orexins regulate the reward-seeking pathway and also play a role in drug addiction. The aim of this study was an investigation of the changes in serum level of orexin-A as well as changes in the functional brain network in heroin use disorder (HUD) patients undergoing harm reduction therapy (HRT). Twenty-five HUD patients undergoing HRT that included methadone and buprenorphine, and 31 healthy control (HC) subjects, were enrolled for this study. Serum orexin-A levels and brain-derived neurotrophic factor were measured with assay kits. The functional brain network in HUD patients and HC was investigated and assessed using seed-based analysis and functional brain MRI scans. t Tested orexin-A levels were found to be significantly higher in HUD patients undergoing HRT than in HCs (P < .05). Analysis showed the functional activity of the right ventral anterior insula (RVAI) in HUD patients to be significantly lower than in HCs (P < .05, Family-Wise Error) corrected). In addition, the internetwork functional connectivity was significantly lower in the left nucleus accumbens and left dorsal anterior insula in the HUD subjects than in HCs (P < .05, Family-Wise Error corrected). In this study, no significant correlation between orexin-A levels and functional brain networks was found. However, the results suggest that HRT might increase orexin-A levels and decrease functional activity in RVAI in HUD patients.

Topics: Brain; Buprenorphine; Harm Reduction; Heroin; Heroin Dependence; Humans; Methadone; Orexins

The ongoing rise in opioid use disorder (OUD) has made it imperative to better model the individual variation within the human population that contributes to OUD vulnerability. Using animal models that capture such variation can be a useful tool. Individual variation in novelty-induced locomotion is predictive of substance use disorder (SUD) propensity. In this model, rats are characterized as high-responders (HR) or low-responders (LR) using a median split based on distance travelled during a locomotor test, and HR rats are generally found to exhibit a more SUD vulnerable behavioral phenotype.. The HR/LR model has commonly been used to assess behaviors in male rats using psychostimulants, with limited knowledge of the predictive efficacy of this model in females or the use of an opioid as the reward. In the current study, we assessed several behaviors across the different phases of drug addiction (heroin taking, refraining, and seeking) in over 500 male and female heterogeneous stock rats run at two geographically separate locations. Rats were characterized as HRs or LRs within each sex for analysis.. Overall, females exhibit a more OUD vulnerable phenotype relative to males. Additionally, the HR/LR model was predictive of OUD-like behaviors in male, but not female rats. Furthermore, phenotypes did not differ in anxiety-related behaviors, reacquisition of heroin-taking, or punished heroin-taking behavior in either sex.. These results emphasize the importance of assessing females in models of individual variation in SUD and highlight limitations in using the HR/LR model to assess OUD propensity.

Topics: Analgesics, Opioid; Animals; Exploratory Behavior; Female; Heroin; Heroin Dependence; Humans; Male; Motor Activity; Rats

The phenomenon of brain recovery after long-term abstinence has been reported in substance use disorders. However, few longitudinal studies have been conducted to observe the potential recovery in heroin users, and little is known about the neural mechanism underlying the decreased craving after prolonged abstinence. The 8-month longitudinal study was carried out in 29 heroin users and 30 healthy controls. By choosing the L_DLPFC, which was activated by the heroin cue as the seeding region, different brain connection patterns were compared between healthy controls and heroin users by using Granger causality analysis (GCA) at baseline. Then, a paired t test was employed to detect the potential recovery of L_DLPFC circuits after prolonged abstinence. The visual analog scale (VAS) and trail-making test-A (TMT-A) were adopted to investigate craving and cognitive control impairment, respectively. The neuroimaging changes were then correlated with behavioral improvements. Similar analyses were applied for the mirrored right DLPFC to verify the lateralization hypothesis of the DLPFC in addiction. In the longitudinal study, enhanced GCA coefficients were observed in the L_DLPFC-R_insula circuit of heroin users after long-term abstinence and were associated with craving score changes. At baseline, decreased GCA coefficients from the left DLPFC to the bilateral SMA and right putamen, together with the reduced GCA strength from the bilateral OFC to the left DLPFC, were found between HUs and HCs. Our findings extended the brain recovery phenomenon into the field of heroin and suggested that the increased regulation of the L_DLPFC over the insula after prolonged abstinence was important for craving inhibition.

Topics: Craving; Dorsolateral Prefrontal Cortex; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Magnetic Resonance Imaging

Heroin pipe distribution may encourage people who use heroin (PWUH) to transition from injecting to smoking heroin, reducing harms associated with injection drug use. A syringe services program (SSP) in Seattle, Washington, led by people who use drugs developed a heroin pipe distribution program.. We conducted a pretest-posttest quasi-experimental study to evaluate the impact of heroin pipe distribution on drug consumption behaviors among PWUH between March and December 2019. SSP clients were surveyed during three weeklong timepoints before and four weeklong timepoints after heroin pipe distribution. Primary outcomes were change in proportion of SSP clients who exclusively injected heroin, exclusively smoked heroin, and both injected and smoked heroin in the past seven days comparing the pre- and post-intervention periods.. Across the seven observation timepoints, 694 unique respondents completed 957 surveys. Multiple responses from a single respondent in a given period were collapsed, resulting in 360 pre-intervention and 430 post-intervention records. Heroin use was reported in over half of pre-intervention (56%, 201/360) and post-intervention records (58%, 251/430). Compared to pre-intervention behaviors, the proportion of respondents who exclusively injected heroin was lower after the start of heroin pipe distribution (32%, 80/251 vs 43%, 86/201, p = 0.02), while the proportion of respondents who both injected and smoked heroin was higher (45%, 113/251 vs 36%, 72/201, p = 0.048). Just under half (44%, 110/251) of respondents who used heroin during the post-intervention period used a heroin pipe obtained from the SSP, of which 34% (37/110) reported heroin pipe distribution had reduced their heroin injection frequency. Self-reported hospitalization for a pulmonary cause was not associated with using a heroin pipe.. The proportion of SSP clients who exclusively injected heroin was lower after implementation of heroin pipe distribution. Randomized studies with longer follow-up are needed to investigate whether heroin pipe distribution reduces heroin injection and improves health outcomes associated with drug use. Limited intervention exposure, loss to follow-up, and pipe availability from other sources pose methodological challenges to evaluations of route transition interventions in community settings. This pilot highlights the potential for organizations led by people who use drugs to develop, implement, and evaluate novel public health programming.

Topics: Drug Users; Heroin; Heroin Dependence; Humans; Public Health; Substance Abuse, Intravenous

Methadone and buprenorphine are the two maintenance treatments in opiate addicts authorised in France since the end of the 1990's. More recently, some African countries such as Senegal have implemented a new health policy focused on reducing the risks by encouraging the use of methadone as maintenance treatment. The objectives of maintenance therapy are to reduce morbidity and mortality related to the consumption of heroin and other street opioids, to promote the integration of drug users into the healthcare system, and more generally, to improve their social integration. However, this strategy might have limitations in practice. Here, we report the experience of the Integrated Addiction Treatment Center in Dakar, Senegal, and discuss ethical considerations at both the individual and collective levels, which may improve care of opiate-dependent users in practice, especially in Africa.. Traitement de substitution des usagers dépendants des opiacés - L’expérience du Centre de prise en charge intégré des addictions de Dakar.. La méthadone et la buprénorphine sont les deux traitements de substitution des opiacés autorisés en France depuis la fin des années 1990. Plus récemment, certains pays africains, comme le Sénégal, ont mis en place une nouvelle politique de santé axée sur la réduction des risques, en encourageant le recours aux traitements de substitution des opiacés. Les objectifs de la substitution sont de réduire la morbi-mortalité liée à la consommation d’héroïne ou d’autres opioïdes de rue, de favoriser l’insertion des usagers de drogue dans le système de soins, et, plus généralement, de faciliter leur insertion sociale. Cette nouvelle stratégie trouve néanmoins des limites dans la pratique. Nous rapportons dans cette revue l’expérience du Centre de prise en charge intégré des addictions de Dakar, au Sénégal, et proposons une réflexion éthique, tant individuelle que collective, afin d’améliorer le traitement de substitution des opiacés, notamment en Afrique.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Opiate Alkaloids; Senegal

Persons with dual severe opioid and cocaine use disorders are at risk of considerable morbidity, and the bidirectional relationship of escalation of mu-opioid agonists and cocaine use is not well understood. The aim of this study was to examine the bidirectional relationship between escalation of heroin and cocaine use in volunteers dually diagnosed with opioid and cocaine dependence (OD + CD). Volunteers from New York with OD + CD (total

Topics: Adolescent; Analgesics, Opioid; Cocaine; Cocaine-Related Disorders; Female; Heroin; Heroin Dependence; Humans; Infant; Male; Opioid-Related Disorders

A case of feline intoxication and fatality with the illicit drug heroin is described. A 5-year-old castrated male domestic shorthair cat was recently diagnosed with an active pneumonitis and left at home for a couple of days under the care of another resident. Upon return, the owner found his cat dead with strong suspicion of foul play. The cat was necropsied by a local veterinary clinic to retrieve the liver for diagnostic toxicology. The postmortem liver sample screened positive for 6-acetylmorphine and 6-acetylcodeine by gas chromatography mass spectrometry. Deconvolution techniques were applied to chromatograms, which revealed the additional presence of morphine and mirtazapine. Subsequent quantitation of mirtazapine, heroin, morphine, 6-acetylmorphine and 6-acetylcodeine was performed by gas chromatography--tandem quadrupole mass spectrometry. Although companion animal fatalities arising from toxicities are a likely consequence of drug abuse in a home, this is the first reported case of a malicious feline fatality resulting from heroin with quantitation of heroin metabolites.

Topics: Animals; Cats; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Liver; Male; Morphine; Morphine Derivatives; Substance Abuse Detection; Tandem Mass Spectrometry

Pregabalin (PGL) is a gabapentinoid used to treat epilepsy, neuropathic pain and generalized anxiety disorder. PGL is also misused by heroin users as it enhances the effects of heroin. While it is thought those who misuse PGL take it in amounts greater than the recommended therapeutic dose, it is unknown whether there is a significant difference between the amounts of PGL used by heroin users compared to non-heroin users. This study hypothesized that the PGL concentrations in postmortem (PM) samples taken from heroin users positive for PGL would be higher than those in non-heroin users. Between 1 January 2016 and 31 December 2016, a routine drug screen and a specific screen for PGL were carried out on femoral-vein bloods from 3,750 PM Coroners' cases. Of the cases screened, 354 were heroin users, of which 264 cases were negative for gabapentinoids and therefore used as the control-heroin-user group. PGL was positive in 229 cases, of which 69 were heroin users and 160 were non-heroin users. On comparing the PGL concentrations, statistically higher concentrations were observed in the heroin users compared to non-heroin users (P = 0.002). There was no correlation between the concentrations of PGL and morphine (from heroin) in the heroin users (P = 0.95), and the amount of heroin (morphine) consumed was not dependant on whether PGL was consumed or not (P = 0.98). The prevalence of anti-depressants, benzodiazepines, methadone and non-heroin-related opioids was seen to be significantly higher in heroin users that were positive for PGL than the control-heroin users (P = < 0.001 for all drugs). This study suggests that heroin users are using greater amounts of PGL compared to non-heroin users; however, the magnitude of the difference in use may not be sufficient to conclude that heroin users are at substantially greater risk of PGL toxicity compared to non-heroin users. Results indicate that heroin users who take PGL are more likely to use multiple depressant drugs, hence increasing the risk of multi-drug toxicity and death in this population.

Topics: Autopsy; Heroin; Heroin Dependence; Humans; Morphine; Pregabalin

Heroin overdose is a leading cause of mortality among drug users. This paper aims to identify individual and contextual factors associated with lethal and non-lethal heroin-related overdoses on the basis of case reports and semi-structured proxy interviews. Typical patterns within these cases are determined by means of cluster analysis.. Within the CaRe (Case Reports of heroin-related overdoses) study, case reports (100 proxy reports of overdose events from 36 different facilities) were gathered and evaluated as part of a nationwide survey of experts conducted in Germany in 2019. Following initial descriptive analyses a two-step cluster analysis with the four binary variables of gender, age, time and place was conducted to identify patterns within the reported cases.. The case reports grouped into five clusters: 1) Younger male drug users, found in a public space during the daytime; 2) Female drug users; 3) Older male drug users, found in a public space during the daytime; 4) Drug users found at home at night; 5) Drug users found outside at night. Overdoses by female drug users and those which occurred at home and/or at night were significantly more likely to have a fatal outcome.. Future prevention and intervention measures should aim to consider the context, i.e. typical constellations of risk, and attempt to inhibit this through appropriate counter measures.

Topics: Drug Overdose; Drug Users; Female; Heroin; Heroin Dependence; Humans; Male; Opiate Overdose

Opioid use disorder is a complicated brain disease with high heritability. The underlying mechanisms of the genetic underpinnings in the susceptibility and treatment response of opioid use disorder remain elusive.. To reveal the potential associations of genotypes and gene methylations of dopaminergic system genes, as well as roles of them in opioid use disorder. In the present study, we detected the DNA methylation in the promoter regions of five representative dopaminergic system genes (DRD1, DRD2, SLC6A3, TH, and COMT) between 120 patients with heroin use disorder in methadone maintenance treatment (MMT) program and 111 healthy controls. The associations of 25 SNPs in the above genes and methylation of 237 CpG sites, known as methylation quantitative trait loci (mQTLs), were determined. Then, the correlations of the above mQTLs and traits of heroin use disorder were analyzed in a sample set of 801 patients with heroin use disorder and 930 healthy controls.. Our results demonstrated that several mQTLs in the DRD1 and DRD2 genes were identified both in the heroin use disorder and healthy control groups. Interestingly, rs4867798-CpG_174872884 and rs5326-CpG_174872884 in the DRD1 gene were the unique SNP-CpG pairs in the patients with heroin use disorder. Furthermore, mQTL rs5326 was associated with the susceptibility and effective dosage of MMT for heroin use disorder, and demonstrated allele-specific correlation with the expression of the DRD1 gene in the human caudate.. Our findings suggest that some mQTLs may be associated with traits of opioid use disorder by implicating the DNA methylation and gene expression.

Topics: DNA Methylation; Dopamine Plasma Membrane Transport Proteins; Heroin; Heroin Dependence; Humans; Methadone; Polymorphism, Single Nucleotide; Quantitative Trait Loci

Heroin is a semi-synthetic opioid that is commonly abused drugs in the world. It can cause hepatic injury and lead to multiple organs dysfunction to its addicts. Only a few reports exist on the metabolic changes and mechanisms in the liver of heroin-addicted mice with hepatic injury.. Twelve adult male Kunming mice (30-40 g) were divided into two groups randomly. The mice in the heroin-addicted group were injected subcutaneously in the first ten days with an increased dosage of heroin from 10 mg/kg to 55 mg/kg. The dosage was then stabilized at 55 mg/kg for three days. The control group was injected with the same amount of saline in the same manner. The hepatic injury was confirmed through the combination of histopathological observation and aminotransferase (AST) and alanine aminotransferase (ALT) determination. The withdrawal symptoms were recorded and used for assessment of heroin addiction. Eventually, liver metabolic biomarkers of heroin-addicted mice with hepatotoxicity were measured using UHPLC-MS/MS.. Biochemical analysis and histopathological observation showed that heroin-addicted mice had a liver injury. The liver metabolites of heroin-addicted mice changed significantly. Metabonomics analysis revealed 41 metabolites in the liver of addicted heroin mice as biomarkers involving 34 metabolic pathways. Among them, glutathione metabolism, taurine and hypotaurine metabolism, vitamin B2 metabolism, riboflavin metabolism, and single-carbon metabolism pathways were markedly dispruted.. Heroin damages the liver and disrupts the liver's metabolic pathways. Glutathione, taurine, riboflavin, 4-pyridoxate, folic acid, and methionine are important metabolic biomarkers, which may be key targets of heroin-induced liver damage. Thus, this study provides an in-depth understanding of the mechanisms of heroin-induced hepatotoxicity and potential biomarkers of liver damage.

Topics: Animals; Animals, Outbred Strains; Biomarkers; Chemical and Drug Induced Liver Injury; Heroin; Heroin Dependence; Liver; Male; Metabolomics; Mice; Phenotype

Intramuscular (IM) injection of drugs is associated with high rates of injecting-related injuries and diseases. However, little is known about the role of this route of administration in heroin-assisted treatment. The aim of this study was to determine the prevalence of IM diacetylmorphine administration and associated complications as well as to explore patients' views and opinions on the topic and the underlying reasons for this practice.. The research site was a Swiss outpatient treatment centre specialised in heroin-assisted treatment. We conducted in-depth interviews with two patients who intramuscularly inject diacetylmorphine. Interviews were analysed qualitatively, and emerging themes were used to develop a 38-item questionnaire on IM injections. We then offered this questionnaire to all patients in the treatment centre.. Five main themes emerged from the in-depth interviews: poor venous access, side effects, subjective effects, procedure for IM injection, and consideration of alternatives to IM. These themes covered the rationale for using this route of administration, complications, subjective effects of IM diacetylmorphine, hygiene and safety measures as well as alternative routes of administration. Fifty-three patients filled in the questionnaire. The lifetime prevalence of IM injections was 60.4% (n = 32) and 34.4% (n = 11) of the patients stated that IM injection was their primary route of administration. No participant reported using the IM route for street drugs. The main reason for IM injections was poor vein access. Other reasons given were time saving and less risk of injuries. Complications included induration of muscle tissue and pain, whereas more severe complications like thrombosis and infections of the injection site were reported much less often.. As the population of opioid-dependent individuals is aging and the deterioration of access veins is likely to increase, the frequency of IM injecting will equally increase. Even though our data show that the IM injection of diacetylmorphine in a clinical setting is a common practice and appears to be relatively safe, research on alternative routes of administration is needed to provide potentially less harmful alternative routes of administration in heroin-assisted treatment.

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Illicit Drugs; Injections, Intramuscular

Different substance dependences have common effects on reward pathway and molecular adaptations, however little is known regarding their shared genetic factors. We aimed to identify the risk genetic variants that are shared for substance dependence (SD). First, promising genome-wide significant loci were identified from 3296 patients (521 alcoholic/1026 heroin/1749 methamphetamine) vs 2859 healthy controls and independently replicated using 1954 patients vs 1904 controls. Second, the functional effects of promising variants on gene expression, addiction characteristics, brain structure (gray and white matter), and addiction behaviors in addiction animal models (chronic administration and self-administration) were assessed. In addition, we assessed the genetic correlation among the three SDs using LD score regression. We identified and replicated three novel loci that were associated with the common risk of heroin, methamphetamine addiction, and alcoholism: ANKS1B rs2133896 (P

Topics: Alcoholism; Amphetamine-Related Disorders; Animals; Heroin; Heroin Dependence; Humans; Methamphetamine; Rats

Treatment guidelines emphasize patients' readiness for transitioning from opiate substitution treatment (OST) to opiate withdrawal and abstinence. Psychological preparedness indicators for this transition were examined.. Patients (all male) were recruited from three treatment settings: prison, an inpatient detoxification unit, and an outpatient clinic. Time 1 (T1) was admission to methadone-assisted withdrawal in all settings. Time 2 (T2) was a 6-month follow-up. With n = 24 at T1 for each group (N = 72), a battery of instruments relevant to psychological preparedness was administered.. At T1, inpatients had higher self-efficacy beliefs for successful treatment completion than prison patients. For patients contactable at T2, T1 self-efficacy positively predicted T2 opiate abstinence. No other variable improved prediction. T1 SOCRATES (Stages of Change Readiness and Treatment Eagerness Scale) ambivalence scores, age, and lifetime heroin use duration predicted maintenance of contact or not with treatment services and contactability by the researcher. Measures of mood did not differ between groups at T1 or predict T2 outcomes.. Self-efficacy beliefs are a potentially useful indicator of readiness for transitioning from OST to a medically assisted opiate withdrawal and subsequent abstinence. Ambivalence regarding change, age, and lifetime heroin use duration are potentially useful predictors of patients maintaining contact with services, and of being retained in research.. These findings advance existing literature and knowledge by highlighting the importance of self-efficacy in psychological preparedness for opiate abstinence, and the predictive utility to clinicians of this and other variables measurable at admission, in the clinical management of opiate users. (© 2020 The Authors. The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry). (Am J Addict 2021;30:11-20).

Topics: Adult; Analgesics, Opioid; Deprescriptions; Heroin; Heroin Dependence; Humans; Inpatients; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Outpatients; Prisoners; Self Efficacy; Substance Withdrawal Syndrome

Quality of life (QOL) is a relevant and quantifiable outcome of drug dependence treatment. We assessed health-related QOL for people released from three centre-based compulsory treatment (CCT) centres in Vietnam, using the EQ-5D. The study aimed to examine the prognostic value of health-related QOL in relation to time to relapse to heroin use among the participants.. Two hundred and eight CCT participants with heroin dependence were interviewed at release, and at 3, 6 and 12 months post-release. Health-related QOL was measured with the EQ-5D. Kaplan-Meier survival models were fitted using Cox modelling to examine the rate, timing and prediction of the number of days to heroin relapse and to examine the predictability of the health-related QOL measures for days to relapse. Relapse was defined as first time of heroin use.. The study found a substantial relapse rate (85.6%) among participants within 12 months following release from CCT centres; the mean number of days to relapse was 57.7 (SD = 31.6). There was no statistically significant change over time in the mean values of health-related QOL (P = 0.11). While the total index score (across the five pre-specified EQ-5D domains) did not have a significant effect in predicting cumulative relapse, lower scores on the Visual Analogue Scale of the EQ-5D were significantly (P < 0.05) predictive of cumulative relapse, with adjusted hazard ratios for relapse of 0.987 (P = 0.013).. EQ-5D Visual Analogue Scale score is a useful predictor of cumulative heroin relapse among participants released from CCT centres.

Topics: Heroin; Heroin Dependence; Humans; Male; Quality of Life; Recurrence; Rehabilitation Centers; Surveys and Questionnaires; Vietnam

Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long-term abstinence (LA) would improve the coupling among three core brain networks (salience, default mode, and executive control) and decrease craving in treated heroin addicts. Forty-three heroin addicts with LA, 27 heroin addicts with short-term abstinence (SA), and 46 demographically matched healthy controls (HC) participated in the resting-state functional magnetic resonance imaging study. The authors compared the functional connectivity among the three groups and examined how the coupling among salience, default mode, and executive control networks related to duration of abstinence and craving before and after drug cue exposure among heroin addicts. Compared with the SA group, with a tendency toward the HC group, the LA group showed lower drug cue-induced craving, stronger connectivity between the dorsal anterior cingulate cortex (a key node of salience network) and left dorsolateral prefrontal cortex and right posterior parietal cortex (key nodes of executive control network), and stronger connectivity between the right dorsolateral prefrontal cortex and precuneus (a key node of default mode network). Meanwhile, the right dorsolateral prefrontal cortex-precuneus connectivity positively correlated with duration of abstinence. The LA and SA groups demonstrated lower connectivity between the left anterior insula (a key node of salience network) and dorsolateral prefrontal cortex and lower connectivity within the left dorsolateral prefrontal cortex, compared with the HC group. Our findings revealed that LA is associated with lower drug cue induced craving and improve the coupling among the three core brain networks in heroin addicts.

Topics: Adult; Brain; Brain Mapping; Craving; Cues; Dorsolateral Prefrontal Cortex; Gyrus Cinguli; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Young Adult

Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of corticothalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.

Topics: Animals; Behavior, Addictive; Cerebral Cortex; Clozapine; Drug-Seeking Behavior; Food Deprivation; Heroin; Heroin Dependence; Male; Motor Activity; Narcotics; Neural Pathways; Nucleus Accumbens; Rats; Rats, Long-Evans; Recurrence; Self Administration; Substance Withdrawal Syndrome; Thalamus

Heroin dependence may result in suppression of adaptive immune responses. Previously, we demonstrated an increase in relative numbers of inhibitory CD4

Topics: Adult; Analgesics, Opioid; Cell Proliferation; Cytokines; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; T-Lymphocytes, Regulatory

There has long been an international interest in the eradication of drug markets-particularly heroin markets-given their documented connection to the deterioration of local community and social amenity. Recent interest in focused drug law enforcement strategies has reinvigorated debate about the potential for deterrence; however, there exists no large-scale effort to document the risk perceptions of those who transact in heroin markets.. We use data from 2,257 police detainees interviewed as part of the Australian Institute of Criminology's (AIC) Drug Use Monitoring in Australia (DUMA) program. We employ a multilevel generalised ordinal logistic regression model to explore the geographical and temporal heterogeneity of risk, controlling for individual demographic covariates.. With one exception, we find a surprising degree of homogeneity at the high end of the risk perception scale, with between 30 and 35 percent of respondents rating their local heroin market as very risky. At the low end, there was greater geographical and temporal variability with between 15 and 30 percent of respondents rating their market as not at all risky. One location stands out as anomalous, being perceived as considerably more risky. Of the demographic and drug-use covariates, only age and gender were statistically significant. Neither the length nor frequency of association with the heroin market predicted lower levels of risk perception.. A little over half of all heroin market participants consider transacting in their local market to be somewhat or very risky-the others consider it not at all or only a little risky. With few exceptions, this broad pattern appears consistent over time and between geographical locations, although an individual's personal perception is not tied to their degree of exposure to the heroin market. The policy implications of these findings are discussed.

Topics: Australia; Heroin; Heroin Dependence; Humans; Perception; Police; Self Report

The striatum mediates reward processing in addiction, and previous fMRI (functional Magnetic Resonance Imaging) studies have revealed abnormal striatofrontal functional connectivity in heroin addiction. However, little is known about whether there is abnormal structural connectivity of the striatal circuit in heroin addiction. This study investigated the structural connectivity of striatal circuits in abstinent heroin-dependent individuals (HDIs) without methadone treatment.. Forty-three (age: 38.8 ± 7.1) male HDIs and twenty-one (age: 42.4 ± 7.9) matched healthy controls underwent high-resolution T1 and whole-brain diffusion tensor imaging (64 directions) magnetic resonance imaging. Connectivity-based seed classification probabilistic tractography was used to detect the tract strengths of striatal circuits with 10 a priori target masks. Tract strengths were compared between groups and correlated with impulsivity behavior, evaluated using the Barratt Impulsivity Scale (BIS), and craving, measured on visual analogue scale (VAS).. HDIs showed significantly weaker tract strength of the left striatum-medial orbitofrontal cortex (mOFC) (Bonferroni corrected, p < 0.05/20 = 0.0025) and significantly higher BIS total, attention, motor, and non-planning scores (Bonferroni corrected, p < 0.05/4 = 0.0125) than controls. In HDIs, negative correlations were observed between the left striatum- mOFC tract strengths and the BIS total, attention and non-planning scores (r. HDIs displayed decreased structural connectivity of the striatum-mOFC circuit and higher impulsivity. Higher impulsive behavior was associated with decreased left striatal circuit connectivity. These findings suggest that the striatal circuit tract strengths might be a novel potential biomarker in heroin and, potentially, general opioid addiction.

Topics: Adult; Behavior, Addictive; Biomarkers; Brain; Brain Mapping; Case-Control Studies; Cerebral Cortex; Corpus Striatum; Craving; Diffusion Tensor Imaging; Gyrus Cinguli; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Magnetic Resonance Imaging; Male; Middle Aged; Opioid-Related Disorders; Reward

Cocaine and heroin cause impairment of neural plasticity in the brain including striatum. This study aimed to identify genes differentially expressed in the striatum of cynomolgus monkeys in response to cocaine and heroin. After chronic administration of cocaine and heroin in the monkeys, we performed large-scale transcriptome profiling in the striatum using RNA-Seq technology and analysed functional annotation. We found that 547 and 1238 transcripts were more than 1.5-fold up- or down-regulated in cocaine- and heroin-treated groups, respectively, compared to the control group, and 3432 transcripts exhibited differential expression between cocaine- and heroin-treated groups. Functional annotation analysis indicated that genes associated with nervous system development (NAGLU, MOBP and TTL7) and stress granule disassembly (KIF5B and KLC1) were differentially expressed in the cocaine-treated group compared to the control group, whereas gene associated with neuron apoptotic process (ERBB3) was differentially expressed in the heroin-treated group. In addition, IPA network analysis indicated that genes (TRAF6 and TRAF3IP2) associated with inflammation were increased by the chronic administration of cocaine and heroin. These results provide insight into the correlated molecular mechanisms as well as the upregulation and down-regulation of genes in the striatum after chronic exposure to cocaine and heroin.

Topics: Animals; Cocaine; Cocaine-Related Disorders; Corpus Striatum; Disease Models, Animal; Female; Gene Expression Regulation; Heroin; Heroin Dependence; Humans; Kinesins; Macaca fascicularis; Neuronal Plasticity; RNA-Seq; Self Administration; Transcriptome

The neural substrates underlying the relapse behavior of heroin dependents (HD) who received long-term methadone maintenance treatment (MMT) have yet to be thoroughly expounded. This study investigated the relapse-related intrinsic functional hubs of HD and their functional integration feature at whole brain network level.. 57 male HD receiving MMT and 49 matched healthy controls (HC) were enrolled. All of the subjects received resting-state functional magnetic resonance imaging scan. And the 57 patients were assigned a 26-month follow-up for collecting illegal drug use information. Of them, 11 were non-relapsers and 46 relapsers. We analyzed the voxel-based degree centrality (DC) to reveal the differences in nodule centrality between HD and HC, conducted Pearson partial-correlation analysis to confirm the relationship between relapse frequency and DC value of the nodes with significant intergroup differences, and finally compared the functional connectivity (FC) of the relapse-related hubs between non-relapsers and relapsers.. We found the DC values of right insula and left nucleus accumbens (NAc) were negatively correlated with relapse frequency. Compared with the non-relapsers, the relapsers had a significant decreased FC between left NAc and inhibitory control circuitry, including left dorsolateral prefrontal cortex, left inferior frontal gyrus and motor regions.. These findings suggest that the neural substrates of relapse vulnerability in HD undergoing MMT are the intrinsic functional hubs of introceptive and reward systems and the latter modulates relapse behavior via interaction with inhibitory control circuit.

Topics: Adult; Brain; Brain Mapping; Cerebral Cortex; Chronic Disease; Female; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Prefrontal Cortex; Recurrence

Opiate addiction is a major health challenge with substantial societal cost. Though harm minimisation strategies have been effective, there is a growing need for new treatments for detoxification and relapse prevention. Preclinical research has found neurokinin 1 (NK. This study aims to assess the impact of NK

Topics: Adult; Amygdala; Analgesics, Opioid; Brain; Brain Mapping; Conditioning, Psychological; Craving; Cues; Female; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Neurokinin-1 Receptor Antagonists; Opiate Alkaloids; Opioid-Related Disorders; Receptors, Neurokinin-1; Reward; Young Adult

Heroin use disorder is a chronic relapsing brain disease containing multiple phenotypes. These phenotypes vary among heroin users and might be influenced by genetic factors. Single-nucleotide polymorphisms (SNPs) of catechol-O-methyltransferase (COMT) and alpha-1-adrenergic receptor (ADRA1A) genes are associated with heroin use disorder. However, it has not been clarified which phenotypes of heroin use disorder are related to these genes. To address this question, we recruited 801 unrelated heroin users and divided them into different subgroups according to four important phenotypes of heroin use disorder. Then 7 SNPs in the functional region of these genes were systematically screened and genotyped using a SNaPshot assay. We found that the A allele of ADRA1A rs1048101 was associated with a shorter duration of transition from first use to addiction. Subjects with the C allele of ADRA1A rs3808585 were more susceptible to memory impairment after heroin use disorder. Subjects with the G allele of COMT rs769224 were more likely to take a higher dose of heroin every day. Our study confirmed the association between polymorphisms of COMT and ADRA1A with those specific phenotypes of heroin use disorder, which will be instructive for the precise treatment of the disease.

Topics: Alleles; Case-Control Studies; Catechol O-Methyltransferase; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Heroin; Heroin Dependence; Humans; Male; Phenotype; Polymorphism, Single Nucleotide

Akt is initially identified as one of the downstream targets of phosphatidylinositol-3 kinase (PI3K) and is involved in morphine reward and tolerance. However, whether phospholyration of Akt (p-Akt) mediates heroin relapse remains unclear. Here, we aimed to explore the role of p-Akt in the nucleus accumbens (NAc) in cue-induced heroin-seeking behaviors after withdrawal. First, rats were trained to self-administer heroin for 14 days, after which we assessed heroin-seeking behaviors induced by a context cue (CC) or by discrete conditioned cues (CS) after 1 day or 14 days of withdrawal. We found that the active responses induced by CC or CS after 14 days of withdrawal were higher than those after 1 day of withdrawal. Meanwhile, the expression of p-Akt in the NAc was also greatest when rats were exposed to the CS after 14 days of withdrawal. Additionally, a microinjection of LY294002, an inhibitor of PI3K, into the NAc inhibited the CS-induced heroin-seeking behaviors after 14 days of withdrawal, paralleling the decreased levels of p-Akt in the NAc. Finally, Akt1 or β-arrestin 2 was downregulated via a lentiviral injection to assess the effect on heroin seeking after 14 days of withdrawal. CS-induced heroin-seeking behavior was inhibited by downregulation of Akt1, but not β-arrestin 2, in the NAc. These data demonstrate that Akt phosphorylation in the NAc may play an important role in the incubation of heroin-seeking behavior, suggesting that the PI3K/Akt pathways may be involved in the process of heroin relapse and addiction.

Topics: Animals; Cues; Drug-Seeking Behavior; Heroin; Heroin Dependence; Male; Nucleus Accumbens; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Reward; Self Administration; Substance Withdrawal Syndrome

Topics: Eye Movement Desensitization Reprocessing; Heroin; Heroin Dependence; Humans

Sub-Saharan Africa is one of the top three regions with the highest rates of opioid-related premature mortality. Nyaope is the street name for what is believed to be a drug cocktail in South Africa although recent research suggests that it is predominantly heroin. Nyaope powder is most commonly smoked together with cannabis, a drug-use pattern unique to the region. Due to the increasing burden of this drug in low-income communities and the absence of human structural neuroimaging data of combination heroin and cannabis use disorder, we initiated an important cohort study in order to identify neuroanatomical sequelae. Twenty-eight male nyaope users and thirty healthy, matched controls were recruited from drug rehabilitation centers and the community, respectively. T1-weighted MRI images were obtained using a 3 T General Electric Discovery and cortical thickness was examined and compared. Nyaope users displayed extensive grey matter atrophy in the right hemispheric medial orbitofrontal, rostral middle frontal, superior temporal, superior frontal, and supramarginal gyri (two-sided t-test, p < 0.05, corrected for multiple comparisons). Our findings indicate cortical abnormality in nyaope users in regions involved in impulse control, decision making, social- and self-perception, and working memory. Importantly, affected brain regions show large overlap with the pattern of cortical abnormalities shown in heroin use disorder.

Topics: Adult; Atrophy; Cannabis; Case-Control Studies; Cerebral Cortex; Cohort Studies; Gray Matter; Heroin; Heroin Dependence; Humans; Illicit Drugs; Magnetic Resonance Imaging; Male; Marijuana Abuse; Neuroimaging; South Africa

α7 Nicotinic acetylcholine receptors are implicated in the reinstatement of drug-seeking, an important component of relapse. We showed previously that the α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, specifically attenuated morphine-primed reinstatement of conditioned place preference in rodents and this effect was mediated in the ventral hippocampus.. The purpose of this study was to evaluate α7 nicotinic acetylcholine receptor antagonism in reinstatement of the conditioned place preference for the more widely abused opioid, heroin, and to compare the effect of α7 nicotinic acetylcholine receptor blockade on reinstatement of heroin-seeking and heroin self-administration in an intravenous self-administration model of addictive behaviour.. Rats were trained to acquire heroin conditioned place preference or heroin self-administration; both followed by extinction of responding. Methyllycaconitine or saline was given prior to reinstatement of drug-primed conditioned place preference, or drug-prime plus cue-induced reinstatement of intravenous self-administration, using two protocols: without delivery of heroin in response to lever pressing to model heroin-seeking, or with heroin self-administration, using fixed and progressive ratio reward schedules, to model relapse.. Methyllycaconitine had no effect on acquisition of heroin conditioned place preference or lever-pressing for food rewards. Methyllycaconitine blocked reinstatement of heroin-primed conditioned place preference. Methyllycaconitine did not prevent drug-prime plus cue-induced reinstatement of heroin-seeking, reinstatement of heroin self-administration, or diminish the reinforcing effect of heroin.. The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, prevented reinstatement of the opioid conditioned place preference, consistent with a role for α7 nicotinic acetylcholine receptors in the retrieval of associative memories of drug liking. The lack of effect of methyllycaconitine in heroin-dependent rats in two intravenous self-administration models suggests that α7 nicotinic acetylcholine receptors do not play a role in later stages of heroin abuse.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Behavior, Addictive; Conditioning, Psychological; Cues; Drug-Seeking Behavior; Extinction, Psychological; Heroin; Heroin Dependence; Male; Nicotinic Antagonists; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reinforcement, Psychology; Reward; Self Administration

Acetyl fentanyl (AF) is a Schedule I fentanyl analog that has been increasingly seen in heroin and fentanyl polydrug toxicity overdoses in Michigan (MI). Drug users are often unaware of the presence of AF in their drugs because it is often sold mixed into or disguised as heroin. High levels of AF in heroin drug products can cause increased incidence of overdose. This article describes data from a longitudinal opioid surveillance program and details 102 decedents in MI who were found to have evidence of heroin in their postmortem blood. A large portion of these decedents were also found to have evidence of fentanyl and AF. Our data further show significant overlap in incidence rates of AF and heroin-related overdose deaths in several MI counties, suggesting that AF is becoming enmeshed in heroin trafficking. Furthermore, we report unprecedented high incidence rates of AF and heroin-related overdose deaths in Calhoun county, and we propose that it is a high-intensity drug trafficking area. Highways US-131 and US-31 are likely used to transport these drugs. More study is needed into the drug trafficking trends in MI to ascertain drug sources and monitor the ever developing and dangerous polydrug heroin combinations.

Topics: Adult; Analgesics, Opioid; Chromatography, Liquid; Drug Overdose; Drug Trafficking; Female; Fentanyl; Forensic Toxicology; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Michigan; Middle Aged; Population Surveillance; Substance Abuse Detection; Tandem Mass Spectrometry

Topics: Breast Neoplasms; Female; Heroin; Heroin Dependence; Humans; Mastectomy; Pain, Postoperative

The choice of opioid-assisted treatments for patients with heroin dependence is particularly diverse in Switzerland. Since 1994, diacetylmorphine assisted treatments are available. The rules for prescribing and dispensing diacetylmorphine, as laid down by the FOPH, are particularly strict, requiring patients to attend the treatment center several times a day. Thanks to a legislative amendment by the Federal Council, it became possible to extend the dispensing of diacetylmorphine during the Covid-19 epidemic, allowing patients to take the treatment with them for longer periods and thus reducing the number of visits to the clinic. The time freed up could then be invested in other activities, allowing therapies to be refocused more on the patients' life project.. L’offre des traitements assistés par opioïdes pour les personnes avec dépendance à l’héroïne est particulièrement diversifiée en Suisse. Les traitements basés sur la prescription de diacétylmorphine y sont ainsi proposés depuis 1994, dont les règles de prescription et de remise au patient régies par l’Office fédéral de la santé publique sont particulièrement strictes, imposant aux patients un passage au centre de soins plusieurs fois par jour. Grâce aux modifications législatives du Conseil fédéral, permettant aux patients d’emporter le traitement pour des durées plus longues pendant la pandémie de Covid-19, les passages à la consultation ont été réduits. Cela a eu pour effet indirect de libérer du temps, qui a pu être investi dans d’autres activités, notamment le recentrage des thérapies davantage autour des projets de vie des patients.

Topics: COVID-19; Heroin; Heroin Dependence; Humans; SARS-CoV-2; Switzerland

Topics: Gene Frequency; Genetic Predisposition to Disease; Genotype; Heroin; Heroin Dependence; Humans; Minisatellite Repeats; Polymorphism, Genetic; Telomerase

Topics: Heroin; Heroin Dependence; Humans; Pharmaceutical Preparations; Prevalence; Research Design

As fatal overdoses from synthetic opioids continue to rise, we need to understand decision-making processes underlying heroin and synthetic opioid use. This study evaluated the influence of sample impurity and fatal overdose risk on hypothetical heroin use. Individuals who currently use heroin (n = 69) were recruited online. Participants completed two probability-discounting tasks evaluating the likelihood of using a sample of heroin based on the likelihood of sample impurity and likelihood of fatal overdose, where greater discounting represented reduced use likelihood. Prior to completing the probability-discounting tasks, participants were randomized to read one of four prompts varying by the presence of information on heroin effects and active (e.g., fentanyl) or inert impurities. Influence of prompts on discounting processes and associations among probability-discounting measures, opioid use behaviors, and dependence severity were evaluated. Heroin use likelihood decreased with increased impurity or overdose risk and in a generally orderly fashion. Discounting was greater (i.e., reduced heroin use likelihood) when overdose risk, compared to sample impurity, was manipulated. Less discounting was associated with more severe opioid dependence. Discounting did not differ among prompts for either task. Individuals might adjust their heroin-use behavior to reduce harm with risk-related information. Greater discounting elicited by overdose relative to impurity risk suggests that equating adulteration and overdose risk is essential for harm reduction. Expanded access to drug checking services, which inform impurity and overdose risk, can reduce fatal overdoses. Due to fear of legal sanctions for these services, legislation and judicial decisions should explicitly protect these services. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Topics: Adult; Analgesics, Opioid; Attitude to Death; Drug Contamination; Drug Overdose; Female; Fentanyl; Harm Reduction; Heroin; Heroin Dependence; Humans; Male; Probability; Risk

Heroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown.. A total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. We performed metabolic profiling of plasma samples based on ultraperformance liquid chromatography coupled to tandem mass spectrometry to explore the potential biomarkers and mechanisms of heroin withdrawal.. Among the metabolites analyzed, omega-6 polyunsaturated fatty acids (linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, n-6 docosapentaenoic acid), omega-3 polyunsaturated fatty acids (docosahexaenoic acid, docosapentaenoic acid), aromatic amino acids (phenylalanine, tyrosine, tryptophan), and intermediates of the tricarboxylic acid cycle (oxoglutaric acid, isocitric acid) were significantly reduced during acute heroin withdrawal. Although majority of the metabolite changes could recover after months of withdrawal, the levels of alpha-aminobutyric acid, alloisoleucine, ketoleucine, and oxalic acid do not recover.. In conclusion, the plasma metabolites undergo tremendous changes during heroin withdrawal. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and withdrawal stages in heroin addicts.

Topics: Adult; Amino Acids, Aromatic; Biomarkers; Case-Control Studies; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Heroin; Heroin Dependence; Humans; Male; Metabolomics; Substance Withdrawal Syndrome; Tricarboxylic Acids

Activity in numerous brain regions drives heroin seeking, but no circuits that limit heroin seeking have been identified. Furthermore, the neural circuits controlling opioid choice are unknown. In this study, we examined the role of the infralimbic cortex (IL) to nucleus accumbens shell (NAshell) pathway during heroin choice and relapse. This model yielded subpopulations of heroin versus food preferring rats during choice, and choice was unrelated to subsequent relapse rates to heroin versus food cues, suggesting that choice and relapse are distinct behavioral constructs. Supporting this, inactivation of the IL with muscimol produced differential effects on opioid choice versus relapse. A pathway-specific chemogenetic approach revealed, however, that the IL-NAshell pathway acts as a common limiter of opioid choice and relapse. Furthermore, dendritic spines in IL-NAshell neurons encode distinct aspects of heroin versus food reinforcement. Thus, opioid choice and relapse share a common addiction-limiting circuit in the IL-NAshell pathway.

Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Behavior, Animal; Brain; Cerebral Cortex; Cues; Decision Making; Drug-Seeking Behavior; Eating; Extinction, Psychological; Food; Heroin; Heroin Dependence; Male; Neural Pathways; Nucleus Accumbens; Opioid-Related Disorders; Rats; Recurrence; Reinforcement, Psychology; Rodentia; Self Administration

Due to their small sample sizes, geographic specificity and limited examination of socio-demographic characteristics, recent studies of methamphetamine use among people using heroin in the United States are limited in their ability to identify national and regional trends and to characterize populations at risk for using heroin and methamphetamine. This study aimed to examine trends and correlates of methamphetamine use among heroin treatment admissions in the United States.. Longitudinal analysis of data from the 2008 to 2017 Treatment Episode Data Set. Descriptive statistics, trend analyses and multivariable logistic regression were used to examine characteristics associated with methamphetamine use among heroin treatment admissions.. United States.. Treatment admissions of people aged ≥ 12 years whose primary substance of use is heroin.. Primary measurement was heroin treatment admissions involving methamphetamine. Secondary measurements were demographics of sex, age, race/ethnicity, US census region, living arrangement and employment status.. The percentage of primary heroin treatment admissions reporting methamphetamine use increased each year from 2.1% in 2008 to 12.4% in 2017, a relative percentage increase of 490% and an annual percentage change (APC) of 23.4% (P < 0.001). During the study period, increases were seen among males and females and among all demographic and geographic groups examined. Among primary heroin treatment admissions reporting methamphetamine use in 2017, 47.1% reported injecting, 46.0% reported smoking, 5.1% reporting snorting and 1.8% reported oral/other as their usual route of methamphetamine use.. Methamphetamine use among heroin treatment admissions in the United States increased from one in 50 primary heroin treatment admissions in 2008 to one in 8 admissions in 2017.

Topics: Adolescent; Adult; Datasets as Topic; Female; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methamphetamine; Middle Aged; Patient Admission; Substance Abuse Treatment Centers; United States; Young Adult

Nationally, it was estimated that 11.4 million people misused opioids in 2017 with more than 47,000 opioid-related deaths. Although medication-assisted treatment (MAT) has been effective in enhancing treatment retention and decreasing frequency of opioid use, relapse rates for opioids and other substances remain high, emphasizing the importance of investigating novel interventions to augment MAT. One potential treatment approach is repetitive transcranial magnetic stimulation (rTMS)-a noninvasive, electrophysiological method of neuromodulation. Recently published studies of rTMS in individuals with alcohol, nicotine, and cocaine use disorder have suggested that this treatment shows promise in reducing cravings and substance use. The literature specific to rTMS and opioid use disorder (OUD) is limited to a single published study in heroin users, which showed that a single session of rTMS to the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving, with a further reduction following 5 consecutive days of rTMS. The following case report involved a 25-year-old Caucasian male diagnosed with OUD and cocaine use disorder. This subject continued to demonstrate ongoing substance use despite participating in comprehensive MAT with buprenorphine/naloxone in combination with psychosocial interventions. He was administered 7 separate sessions of rTMS targeting the left DLPFC. Substance-related cues were presented prior to, during, and following these rTMS administration sessions and the subject rated his substance cravings via a 100-point Visual Analog Scale. When compared with his cue-induced craving ratings, there was a mean reduction in craving for heroin and cocaine by ∼60% to 82% following the 7 administration sessions. Although this is a single case, further investigation of rTMS as an augmentation strategy for OUD and polysubstance use is warranted. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Topics: Adult; Cocaine; Cocaine-Related Disorders; Craving; Cues; Heroin; Heroin Dependence; Humans; Male; Prefrontal Cortex; Substance-Related Disorders; Transcranial Magnetic Stimulation

Opioid addiction has been declared a public health emergency, with fatal overdoses following relapse reaching epidemic proportions and disease-associated costs continuing to escalate. Relapse is often triggered by re-exposure to drug-associated cues, and though the neural substrates responsible for relapse in vulnerable individuals remains ambiguous, the nucleus accumbens (NAc) has been shown to play a central role. NAc direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) can have oppositional control over reward-seeking and associative learning and are critically involved in reinstatement of psychostimulant-seeking. However, whether these pathways similarly regulate reinstatement of opioid-seeking remains unknown, as is their role in modulating motivation to take opioids. Here, we describe a method for classifying addiction severity in outbred rats following intermittent-access heroin self-administration that identifies subgroups as addiction-vulnerable (high-risk) or addiction-resistant (low-risk). Using dual viral-mediated gene transfer of DREADDs, we show that transient inactivation of dMSNs or activation of iMSNs is capable of suppressing cue-induced reinstatement of heroin-seeking in high- but not low-risk rats. Surprisingly, however, the motivation to self-administer heroin was unchanged, indicating a divergence in the encoding of heroin-taking and heroin-seeking in rats. We further show that transient activation of dMSNs or inactivation of iMSNs exacerbates cue-induced reinstatement of heroin-seeking in high- but not low-risk rats, again with no effect on motivation. These findings demonstrate a critical role for dMSNs and iMSNs in encoding vulnerability to reinstatement of heroin-seeking and provide insight into the specific neurobiological changes that occur in vulnerable groups following heroin self-administration.

Topics: Animals; Cues; Extinction, Psychological; Heroin; Heroin Dependence; Nucleus Accumbens; Rats; Reward; Self Administration

Caloric restriction increases the risk of relapse in abstinent drug users. Hormones involved in the regulation of energy balance and food intake, such as leptin and ghrelin, are implicated in drug-related behaviors.. We investigated the role of leptin and ghrelin in the augmentation of heroin seeking induced by chronic food restriction.. Rats self-administered heroin (0.1 mg/kg/infusion) for 10 days followed by 14 days of drug withdrawal. During withdrawal, rats were food restricted to 90% of their original body weight or were given free access to food. In experiment 1, we measured the plasma concentrations of leptin and ghrelin following heroin self-administration and withdrawal. In experiment 2, leptin was administered centrally (2.0 or 4.0 μg; i.c.v.) prior to a heroin-seeking test under extinction conditions. High density of both leptin and ghrelin receptors was previously identified in the ventral tegmental area (VTA), suggesting a direct effect on reward and motivation. Hence, we administered leptin (experiment 3; 0.125 or 0.250 μg/side), or ghrelin receptor antagonist JMV 2959 (experiment 4; 2.0 or 10.0 μg/side) directly into the VTA prior to the heroin-seeking test.. Chronic food restriction significantly decreased plasma levels of leptin and elevated plasma levels of ghrelin. Central administration of leptin had no statistically significant effect on heroin seeking. Intra-VTA administration of either leptin or JMV 2959 dose-dependently and selectively decreased heroin seeking in the food-restricted rats.. Leptin and ghrelin transmission in the VTA can modulate the augmentation of heroin seeking induced by chronic food restriction.

Topics: Animals; Conditioning, Operant; Drug-Seeking Behavior; Food Deprivation; Ghrelin; Heroin; Heroin Dependence; Leptin; Male; Motivation; Rats; Rats, Long-Evans; Self Administration; Ventral Tegmental Area

The majority of opioid-related deaths are accidental. However, the number of opioid-related suicidal deaths is likely under recognized. Presented here is a case of suicide by heroin overdose. The manner of death would have likely been deemed accidental if not for critical information shared by the decedent's family during follow-up telephone interviews between the forensic pathologist and the decedent's family, which included text messages that were sent by the decedent just before his death that were not known at the time of the initial medicolegal death scene investigation. This case highlights that when a forensic pathologist establishes an engaged relationship with the decedent's family, the information elucidated can prove to be invaluable in reaching an informed opinion about the manner of death. For overdose cases, identifying an accurate manner of death allows the design of public health efforts that adequately address the health risks in the community. For aid in the determination of the manner of death for overdose cases, we propose a five-step checklist that may assist forensic pathologists and medicolegal death investigators when approaching similar cases.

Topics: Adult; Communication; Drug Overdose; Heroin; Heroin Dependence; Humans; Male; Narcotics; Professional-Family Relations; Suicide, Completed; Text Messaging

Deficits in response inhibition associated with heroin use could last several months after abstinence in heroin users, and their response inhibition can also be interfered with task-irrelevant drug-related cues. However, it is unclear whether exposure to drug-related cues affects subsequent response inhibition in heroin users following abstinence.. The present study aimed to investigate how drug-related cues with different durations between stimulus presentations, referred to as stimulus onset asynchronies (SOAs), affect subsequent response inhibition in heroin abstainers (HAs) with different length of abstinence.. Sixty-seven male HAs performed a modified Go/NoGo task in which a motor response to frequent Go targets and no response to rare NoGo targets were required and a Go or NoGo target was displayed after either a heroin-related or a neutral picture presented for the 200 ms and 600 ms SOAs.. The HAs responded significantly faster to Go targets following the neutral pictures for the 600 ms SOA compared to other conditions. They also made more commission errors following heroin-related pictures compared to neutral pictures regardless of the SOAs. The shorter-term HAs made more commission errors compared to the longer-term HAs following the 200 ms SOA, and it was only a trend when the SOA was 600 ms. Additionally, negative correlations between the duration of current abstinence and commission errors were observed following cues with the 200 ms SOA.. Impaired response inhibition in HAs can be improved through protracted drug abstinence. However, that effect can be reduced by exposure to drug-related cues, which may increase the risk of relapse.

Topics: Adult; Cues; Heroin; Heroin Dependence; Humans; Inhibition, Psychological; Male; Middle Aged; Photic Stimulation; Reaction Time; Time Factors

Heroin addiction is a chronic relapsing brain disorder with negative social consequences. Histone acetylation serves a role in drug‑induced behavior and neuroplasticity impairment. Brahma/SWI2‑related gene‑1 (BRG1) participates in cerebellar development, embryogenesis and transcriptional regulation of neuronal genes concurrent with histone modifications. However, little is known about the relationship between histone H3 lysine 9 acetylation (H3K9ac) and BRG1 in response to heroin. The present study aimed to assess the contribution of histone 3 lysine 9 acetylation of BRG1 to heroin self‑administration. The present study established a Sprague‑Dawley rat model of heroin self‑administration under a fixed‑ratio‑1 paradigm. Chromatin immunoprecipitation followed by reverse transcription‑quantitative PCR (RT‑qPCR) was used to detect the accumulation of H3K9ac on BRG1 in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) following heroin self‑administration. The relative expression levels of BRG1 were analyzed by RT‑qPCR. H3K9ac at the promoter region of BRG1 was significantly elevated (P=0.002), and the expression of BRG1 in the mPFC increased 1.47‑fold in the heroin self‑administration group compared with the control group. No significant difference in H3K9ac at the BRG1 locus was observed in the NAc (P=0.323), with the expression of BRG1 decreasing 1.38‑fold in the heroin self‑administering rats compared with the control group. H3K9ac is associated with transcriptional activation, and the increased BRG1 expression suggested an essential and novel role for BRG1 and its H3K9ac‑mediated regulation in the mPFC after heroin self‑administration; and this may function through epigenetically modulating the activation of neuroplasticity‑associated genes. This association may provide a novel therapeutic target for the treatment of heroin addiction.

Topics: Acetylation; Animals; Chromatin Immunoprecipitation; DNA Helicases; Epigenesis, Genetic; Heroin; Heroin Dependence; Histone Code; Histones; Lysine; Male; Nucleus Accumbens; Prefrontal Cortex; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; Self Administration; Transcription Factors; Transcriptional Activation

Childhood trauma is of importance for the manifestation of substance-related disorders and maintenance of hypothalamic-pituitary-adrenal (HPA)-axis disorders. Since stress plays a crucial role in opioid compliance and craving, we investigated the immediate effects of diacetylmorphine application on the HPA axis. In particular, adrenocorticotropic hormone (ACTH) and cortisol secretion, as well as satiety regulating proopiomelanocortin peptides α-melanocyte-stimulating hormone (MSH) and β-endorphin (END) in a cohort of opioid-dependent patients in diamorphine maintenance treatment concerning the clinical severity of their childhood trauma.. We compared the serum levels of ACTH, cortisol, MSH, and END in 15 opioid-dependent patients. All participants received treatment with diamorphine and were observed at 5 timepoints before and after injection. We split the cohort into 2 subgroups concerning childhood trauma measured by the Childhood Trauma Questionnaire.. Splitting in 2 subgroups for mild (5) and severe trauma (10), we found that while both groups show a significant reduction of ACTH and cortisol levels over time, slopes display different progressions over time for cortisol (F[1.6] = 9.38, p = 0.02), while remaining identical for ACTH (F[1.6] = 1.69, p = 0.24). Also, levels of both MSH and END were significantly lower in severely traumatized patients.. For the first time, we present a detailed representation of stress- and addiction-related proteins for the first 5 h after diamorphine application, demonstrating the interrelationship between stress hormones and childhood trauma as well as its potential effects on the progression of addictions such as opioid dependence.

Topics: Adrenocorticotropic Hormone; Adult; Adverse Childhood Experiences; beta-Endorphin; Child; Cohort Studies; Female; Heroin; Heroin Dependence; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Stress, Psychological; Surveys and Questionnaires; Wounds and Injuries

Topics: Animals; Compulsive Behavior; Corpus Striatum; Heroin; Heroin Dependence; Nucleus Accumbens; Rats

There is a lack of research examining what prevents people who smoke heroin from transitioning to regular injection. This qualitative study aims to improve understanding of environmental influences preventing people who smoke heroin from transitioning to regular injection.. In-depth, semi-structured interviews (n = 15) were conducted with people who currently smoked heroin but never injected (n = 10) and those who injected on a few occasions but did not transition to regular injection (n = 5) in Northern Ireland. Multiple recruitment strategies were utilized to generate a community-based sample. Interviews were thematically analysed.. Participants identified two main, interconnected influences preventing transition to injecting heroin. Firstly, resistance towards injecting was rooted in micro level perceptions of risks primarily arising from meso level social interactions with people who inject drugs and, to a lesser extent, harm reduction agencies. Secondly, participants identified meso and macro environments defined as changing social contexts and normative beliefs surrounding the acceptability of injecting within their drug-using social networks, facilitated by expanding heron markets, negative interactions with people who inject drugs and new groups of people choosing to smoke heroin due to perceptions of injection risks.. Findings illuminate environmental influences surrounding and shaping drug consumption practices. Harm reduction strategies should develop and implement safer smoking rooms, community and peer interventions, and improve accessibility to opioid substitution therapy and low threshold outreach services to prevent transitioning to regular heroin injecting.

Topics: Adult; Drug Users; Female; Harm Reduction; Heroin; Heroin Dependence; Humans; Male; Northern Ireland; Perception; Qualitative Research; Social Environment; Substance Abuse, Intravenous; Young Adult

It is widely reported that drug addiction involves the strengthening of specific reward circuits through N-methyl-d-aspartic acid receptor (NMDAR)-dependent synaptic potentiation, and several lines of evidence strongly implicate NMDA receptor 2 (NR2) subunits in drug abuse. To explore the potential mechanism of heroin dependence, this study examined changes in the expression levels of NR2 subunits NR2A-D in the prelimbic (PL) region of the medial prefrontal cortex (mPFC) after repeated heroin administration and subsequent abstinence. The conditioned place preference (CPP) test confirmed successful induction of heroin dependence and withdrawal. Western blotting and qRT-PCR revealed no differences in NR2A subunit expression among heroin-exposure, heroin-withdrawal, and control group rats; in contrast, expression of NR2B was significantly higher in the heroin-exposure group, whereas expression levels of NR2C and NR2D were significantly higher in the heroin-withdrawal group relative to the controls. Further studies are needed to identify the functional significance based on alterations of NR2 subunits.

Topics: Animals; Gene Expression; Heroin; Heroin Dependence; Male; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome

Drug abuse is one of the most severe global social and public health problems, especially in China. However, objective blood biomarkers that are easy to detect are still in great need. This study was aim to explore the expression pattern of circulating microRNAs (miRNAs) in subjects with drug addiction and test the potential of altered serum miRNAs as noninvasive diagnostic tools for drug abuse.. Serum samples were obtained from 42 heroin abusers, 42 methamphetamine (MA) abusers and 42 controls. Microarray-based miRNA analysis was first applied to screen unique serum miRNA profiles in drug abusers on a training set of serum samples from 12 heroin abusers, 12 MA abusers and 12 control subjects. The expression levels of selected candidate miRNAs were subsequently verified in individual samples of the training set and further confirmed independently in a validation set of samples from 30 heroin abusers, 30 MA abusers and 30 controls using real-time quantitative polymerase chain reaction (RT-qPCR).. Microarray analysis identified 116 and 109 significantly altered miRNAs in heroin abusers and MA abusers, respectively. Three miRNAs, including let-7b-5p, miR-206 and miR-486-5p, were verified to be significantly and steadily increased in heroin abusers, and miR-9-3p was significantly increased in MA abusers compared with normal controls. The areas under the curve (AUCs) of the ROC curve of these miRNAs ranged from 0.718 to 0.867.. Our study raises the possibility that the altered serum miRNAs could potentially be used as an auxiliary tool to identify individuals in drug abuse and addiction.

Topics: Adult; Amphetamine-Related Disorders; Biomarkers; Female; Gene Expression Profiling; Heroin; Heroin Dependence; Humans; Male; Methamphetamine; MicroRNAs; Middle Aged

Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment.. A single-subject study over 5 years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses.. A clinical research facility. Participant Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction.. Physiological measures of oxygen saturation (SpO. (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20 sec (maximum 56 sec), elevated ETCO. With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Tapering; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Respiratory Insufficiency

There is a robust relationship between anxiety disorders, including post-traumatic stress disorder (PTSD) and substance abuse. In fact, 30-50% of people seeking treatment for substance abuse have a comorbid diagnosis for PTSD. Heroin use is at epic proportions in the USA and is commonly used by people with co-occurring PTSD symptoms and substance use disorder.. Here, we combined animal assays of acute restraint stress and contingent heroin self-administration (SA) to study comorbidity between stress disorders and opioid use disorder and identify shifts in anxiety-like behaviors following stress and/or heroin in response to a stress-conditioned cue. Our objective for this approach was to determine the long-term impact of acute restraint stress and heroin self-administration on stress reactivity and basic reward processes.. We used 2-h acute restraint stress paired with an odor stimulus to condition a stress cue (CS) for testing of subsequent stress reactivity in a burying task and reinstatement and extinction to heroin seeking. Rats were also tested for social place preference for measures of social reward and anxiety-like behaviors.. Stress rats exhibited multiple levels of disrupted behavior including enhanced acquisition of heroin intake and reinstatement in response to the stress CS, as well as delayed extinction in response to the stress CS. All rats developed a social place preference, but stress rats spent more time in nose-to-nose contact with the unfamiliar rat while heroin rats spent time exploring the chamber. In the burying task, stress shortened latencies to bury the CS and increased burying and immobility in male and female rats relative to sham counterparts.. Acute restraint stress results in anxiety-like behaviors and a stress-associated cue is sufficient to reinstate extinguished heroin seeking. This project has the potential to elucidate the complex relationship between stress/anxiety disorders, including some PTSD-like characteristics, and the onset, maintenance, and relapse to heroin seeking.

Topics: Animals; Cues; Extinction, Psychological; Female; Heroin; Heroin Dependence; Male; Odorants; Random Allocation; Rats; Rats, Sprague-Dawley; Restraint, Physical; Self Administration; Stress, Psychological

It is unknown if targeted risk reduction counseling in the health care setting, after documented exposure to fentanyl, can affect behavior change to reduce risks and increase utilization of evidence-based overdose prevention strategies.. We conducted a retrospective analysis of results (7/2018-6/2019) from questionnaire-facilitated counseling by recovery coaches in the emergency department (ED) and primary care settings following disclosure of a urine toxicology positive for fentanyl.. Seventy-five percent of N = 101 respondents were neither aware of nor expecting fentanyl in their substances of use. Fifty-three (70 %) of those initially unaware answered that learning about exposure to and the risks from fentanyl changed their thoughts about reducing or abstaining from use. A greater proportion of patients seen in the ED expressed desire to stop or reduce opioid use as compared to ambulatory clinic patients (91 % vs. 46 %, p < 0.001). Of those not already engaged in treatment, 18 % and 15 % were interested in medication and behavioural health treatment, respectively, and each of them indicated a change in thought based on the counseling. Forty-five percent of individuals not yet receiving naloxone endorsed interest in receiving it, and 22 % of all respondents were somewhat or very interested in access to safe consumption sites.. This study suggests a novel clinical utility in toxicology screens to inform behavior in the setting of illicit fentanyl exposure. In addition to linkages to evidence-based treatment, linkages to harm-mitigating strategies associated with ongoing substance use may be critical to a comprehensive overdose prevention strategy in the clinical setting.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Emergency Service, Hospital; Female; Fentanyl; Health Knowledge, Attitudes, Practice; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Retrospective Studies; Risk Reduction Behavior; Surveys and Questionnaires; Young Adult

The prescribing of heroin has a long and contentious history as a method for treating people with heroin problems. This paper revisits a controversial 'experiment' with heroin prescribing in Northwest England between 1982 and 1995, led by the psychiatrist Dr. John Marks. Marks' work has been shrouded in myth and misinformation for many years and the paper presents an evidence-based reconstruction of this episode, drawing on archival sources, published and unpublished documents, and a small number of interviews with key informants. During this 13-year period, Marks worked across clinics in Liverpool and two neighbouring towns, founding his practice on the long-term maintenance prescribing of opiates, including injectable heroin and smokable heroin reefers. The high media profile of the work, in the context of a febrile local politics in Liverpool, a powerful British addiction psychiatry establishment and an always-heated international politics of drug control, brought immense political pressure and led eventually to the closure of the clinics. The Marks 'experiment' raises important challenges to the premises, practices and philosophy of heroin maintenance - particularly the questions of thresholds and criteria for access, and the purposes of intervention - as well as to the wider regime of prohibitive drug laws.

Topics: Analgesics, Opioid; Drug and Narcotic Control; England; Heroin; Heroin Dependence; Humans

The relationship between past drug use trajectory and long-term relapse risk after rehabilitation among heroin-dependent patients remain understudied. The primary objectives were to identify longitudinal heroin use patterns of heroin-dependent patients, to determine the associative factors with trajectories and to investigate the impact of trajectory groups on relapse after finishing compulsory rehabilitation programs.. A total of 564 heroin-dependent patients were recruited from 4 compulsory rehabilitation facilities in Shanghai, China between 2007 and 2008. The baseline data was linked to participants' follow-up data on relapse from official records. Group-based trajectory model was used to identify distinctive drug use trajectory groups. The association between the identified group and heroin relapse risk was then analyzed to understand the role of past drug use trajectory on relapse.. Five trajectory groups were identified in this cohort: (1) Rapid Decrease (9.9%); (2) Persistent High (32.0%); (3) Slow Decrease (34.1%); (4) Gradual Increase (4.5%); (5) Persistent Low (19.5%). Gender, age, education, and impulsivity were found to be different between the five groups. During the 5 years after discharged from the compulsory program, 291 (59.0%) individuals relapsed. Multivariate logistic regression analysis showed that the persistent high group (OR: 2.77 [1.46-5.24]), slow decrease group (OR: 2.31 [1.32-4.06]) and gradual increase group (OR: 3.50 [1.18-10.39]) was positively associated with the heroin relapse risk when compared to the persistent low group.. Heroin use trajectories vary among heroin-dependent patients in China. The trajectories of heroin use before compulsory rehabilitation are associated with subsequent long-term relapse risk.

Topics: Adult; China; Chronic Disease; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Prognosis; Recurrence

Not Available.

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Illicit Drugs; Italy

Patient satisfaction with methadone or buprenorphine-naloxone can be multidimensionally and specifically assessed by using, respectively, the Scale to Assess Satisfaction with Medications for Addiction Treatment-Methadone for Heroin addiction (SASMAT-METHER) or the SASMAT-Buprenorphine-Naloxone for Heroin addiction (SASMAT-BUNHER). The factor structures of the SASMAT-METHER and SASMAT-BUNHER show substantial commonalities. The objective of the present study is to evaluate the replicability of the SASMAT-METHER factor structure using data from the SASMAT-BUNHER development study in order to obtain an instrument that can be used to compare patient satisfaction with methadone vs. buprenorphine-naloxone.. Secondary analysis of SASMAT-BUNHER data provided by 205 participants in the original validation study of that scale (Pérez de los Cobos et al., 2018). Using the SASMAT-METHER component solution (17 items, 3 factors) as the target structure, a principal component analysis was performed on the data set comprised of the corresponding 17 SASMAT-BUNHER items using an oblique semi-specified Procrustean rotation. Additionally, Tucker congruence coefficients were computed to examine the correspondence between the two solutions.. The factor structures of SASMAT-METHER and the 17-item version of the SASMAT-BUNHER can be considered equal given that the overall Tucker's congruence coefficient of factorial similarity was 0.972, with individual component congruencies ranging from 0.960 to 0.995.. The SASMAT-METHER component solution can serve as a single common tool to compare methadone vs. buprenorphine-naloxone in terms of patient satisfaction. This finding supports the feasibility of using a common metric to specifically assess satisfaction with medications to treat heroin dependence.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Patient Satisfaction; Spain

People who inject drugs often get bacterial infections. Few longitudinal studies have reported the incidence and treatment costs of these infections.. For a cohort of 2335 people who inject heroin entering treatment for drug dependence between 2006 and 2017 in London, England, we reported the rates of hospitalisation or death with primary causes of cutaneous abscess, cellulitis, phlebitis, septicaemia, osteomyelitis, septic arthritis, endocarditis, or necrotising fasciitis. We compared these rates to the general population. We also used NHS reference costs to calculate the cost of admissions.. During a median of 8.0 years of follow-up, 24 % of patients (570/2335) had a severe bacterial infection, most commonly presenting with cutaneous abscesses or cellulitis. Bacterial infections accounted for 13 % of all hospital admissions. The rate was 73 per 1000 person-years (95 % CI 69-77); 50 times the general population, and the rate remained high throughout follow-up. The rate of severe bacterial infections for women was 1.50 (95 % CI 1.32-1.69) times the rate for men. The mean cost per admission was £4980, and we estimate that the annual cost of hospital treatment for people who inject heroin in London is £4.5 million.. People who inject heroin have extreme and long-term risk of severe bacterial infections.

Topics: Adolescent; Adult; Bacterial Infections; Cohort Studies; England; Female; Follow-Up Studies; Health Care Costs; Heroin; Heroin Dependence; Hospitalization; Humans; Incidence; London; Male; Middle Aged; Patient Admission; Severity of Illness Index; Substance Abuse, Intravenous; Young Adult

With opioid abuse becoming a nationwide epidemic, it is important to understand what is contributing to societal views of opioid dependence. Difference in stigmatization of drug users may exist between sexes, ages and type of drugs being used. Social perceptions may impact drug use and recovery. To assess which opioid users are stigmatized most, we administered an experimenter-created vignette that experimentally manipulated the type of opioid (Prescribed Vicodin vs. Non-prescribed Vicodin vs. heroin) as well as the sex of the opioid user (Male vs. Female) and the age of the user (23 years-old vs. 53 years-old) to 4300 people on Amazon's Mechanical Turk (a survey hosting website). Participants were told in a vignette that the target person they were reviewing was "addicted". Results confirmed that the stigmatization of drug use is dependent on a series of items, including type of opioid, as well as the age and sex of the participant. Specifically, prescribed opioids were least stigmatized, while heroin was most stigmatized. Also, there was a significant difference between heroin, non-prescribed Vicodin and prescribed Vicodin use and whether or not participants stigmatized the opioid user as an "addict". More specifically, participants were more likely to identify heroin and non-prescribed Vicodin users as having an opioid addiction. Lastly, young male opioid users were stigmatized more than any other group. Results are discussed.

Topics: Adult; Analgesics, Opioid; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Opioid-Related Disorders; Prescriptions; Stereotyping; Young Adult

: Toxic leukoencephalopathy is a rare illness that causes diffuse white matter destruction, and as a result may mimic psychiatric disorders. Multiple causes have been identified including nerve related injury from exposure to a toxin. When symptoms present, they typically improve after the offending agent is eliminated. However, the clinical presentation in this report is unique in that the syndrome got worse several weeks after the toxin was removed. Research indicates that supportive supplements and vitamins can be used to facilitate neurological recovery. This report outlines a case of toxic leukoencephalopathy following heroin overdose that was treated with vitamin supplementation.

Topics: Adult; Female; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; White Matter

To investigate the manifestations and incidence of headaches caused by heroin in Chinese women.. This was a survey study conducted from 29 June to 3 July 2015 with women attending the Shanxi Drug Rehabilitation Centre for Women (China). All study subjects were newly admitted and had not begun their drug rehabilitation. Demographic characteristics, heroin usage and headache episodes within the previous 3 months were surveyed, especially the presence of a headache within 2 hours of heroin use. Details of the severity, location, premonitory symptoms and characteristics of headaches were recorded.. Of the 90 heroin-dependent patients, 74 experienced headache attacks within 2 hours of heroin use, and the headaches subsided within 72 hours of discontinuation of heroin use. Most heroin-induced headaches were similar to migraines and manifested as pulsating pain in 54 patients (51/74, 68.9%); bilateral pain was reported by 46 patients (46/74, 62.2%). Approximately half of the patients with heroin-induced headaches also reported accompanying symptoms of nausea, vomiting, and light and sound sensitivity.. Heroin-induced headache may eventually be listed as a new class of headache in the International Classification of Headache Disorders.

Topics: Adult; China; Female; Headache Disorders; Heroin; Heroin Dependence; Humans; Incidence; Nausea; Photophobia; Self Report; Severity of Illness Index; Vomiting; Young Adult

Topics: Adult; Amphetamine-Related Disorders; Comorbidity; Cross-Sectional Studies; Female; Hepatitis C; Heroin; Heroin Dependence; Humans; Male; Methadone; Methamphetamine; Middle Aged; Narcotics; Opiate Substitution Treatment; Outcome Assessment, Health Care; Patient Readmission; Program Evaluation; Retrospective Studies; Sex Factors; Young Adult

Whoonga is a smoked heroin-based street drug that first emerged in South Africa a decade ago. While previous scientific reports suggest that use is growing and youth are particularly vulnerable, trajectories of initiation are not well characterized.. In 2015, 30 men undergoing residential addiction treatment for this smoked heroin drug in KwaZulu-Natal, South Africa participated in semi-structured interviews about their experiences using the drug. Interview data were coded using qualitative content analysis.. Participant trajectories to initiating smoked heroin were "vertical" in the context of marijuana use or "horizontal" in the context of other hard drug use. Participants reporting vertical trajectories began smoking heroin as youth at school or in other settings where people were smoking marijuana. Several participants with horizontal trajectories started smoking heroin to address symptoms of other drug or alcohol addiction. Social influences on initiation emerged as an overarching theme. Members of participants' social networks who were smoking or distributing heroin figured prominently in initiation narratives. Surprisingly, references to injection drug use were absent from initiation narratives. Participants reported people who smoke heroin differ from those who inject heroin by race.. Consistent with theories implicating social and structural influences on substance use initiation, people who started smoking heroin had social contacts who smoked heroin and frequented places where substance use was common. Smoked heroin initiation for several participants with horizontal trajectories may have been averted if they accessed evidence-based treatments for stimulant or alcohol use disorders. With increasing reports of heroin use across Africa, a coordinated approach to address this growing epidemic is needed. However, because smoked heroin and injection heroin use occur in distinct risk environments, interventions tailored to people who use smoked heroin will be needed to prevent smoked heroin use, prevent transition to injection use, and mitigate other social harms.

Topics: Adolescent; Alcoholism; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; South Africa; Substance Abuse, Intravenous

Covertly using heroin during methadone maintenance treatment (MMT) is very common among heroin-dependent patients, which has posed threats to the physical health of heroin-dependent patients and social safety. Covertly using heroin may be influenced by many factors, especially social capital. Therefore, we aimed to investigate the relationship between behaviors of covertly using heroin during MMT and social capital heroin-dependent patients in Sichuan Province, China. A cross-sectional study was conducted between October and November 2018, with a total of 581 heroin-dependent patients participating in the study. In addition to socio-demographic characteristics and heroin use related behaviors, the questionnaire also included the measures of social capital: social network (SN), social support (SP), community participation (CP) and social trust (ST). Multivariate logistic regression analyses were used to estimate the association between different measures of social capital and heroin use. The prevalence of covertly using heroin of heroin during MMT was 31.0% among our participants in the 6 months before the study. After adjusting for socio-demographic factors and heroin-use related variables, SN (OR = 0.85, 95% CI: 0.76-0.95), SP (OR = 0.89, 95% CI: 0.83-0.95), and ST (OR = 0.88, 95% CI: 0.81-0.95) were significantly associated with heroin use. Results suggest that social capital may have a protective effect on behavior of covertly using heroin during MMT, which should be consider in the interventions for heroin-dependent patients, in order to reduce the incidence of heroin use during MMT as well as improve the compliance of MMT.

Topics: Adult; China; Community Participation; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Patient Compliance; Prevalence; Social Capital; Social Networking; Social Support

Cholinergic systems modulate dopaminergic function in brain pathways are thought to mediate heroin addiction. This study investigated whether huperzine A, an acetylcholinesterase inhibitor, has beneficial effects on heroin reward and heroin-seeking behavior. Rats were trained to self-administer heroin (50 μg/kg/infusion) under the fixed ratio 1 schedule for 14 days and then drug-seeking was extinguished for 10 days, after which reinstatement of drug-seeking was induced by conditioned cues or heroin priming. Acute treatment with huperzine A at dose from 0.05 to 0.2 mg/kg potently and dose-dependently suppressed the cue- and heroin-induced reinstatement of heroin-seeking behavior following extinction. Huperzine A at these doses failed to alter either heroin rewarding effect or spontaneous locomotion activity. The study demonstrated that acute treatment with huperzine A inhibited heroin-seeking behavior, suggesting that huperzine A may be used as an adjuvant treatment for heroin relapse and addiction.

Topics: Alkaloids; Animals; Behavior, Animal; Cholinesterase Inhibitors; Cues; Drug-Seeking Behavior; Heroin; Heroin Dependence; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Reward; Sesquiterpenes

A common phenomenon shows that ingestion of opium poppy shell-containing drugs can result in a "false-positive" urinalysis test result for mandatory or workplace heroin abuse screening. Owing to the short detection window (8 h in urine) of the characteristic heroin metabolite 6-monoacetylmorphine (6-MAM) confirmation or exclusion of heroin abusers still presents major challenges for toxicologists. In this work, we developed an ultra-performance liquid chromatography-time-of-flight mass spectrometry method (UPLC-TOF-MS) with online data acquisition and multiple post-data-mining technologies combined with a multivariate statistical and batch validation analysis workflow to assess the characteristic urine metabolites of heroin abusers. Based on the proposed methods, 28 characteristic metabolites were structurally identified, and their fragmentation patterns and metabolite pathways were also summarized. Correlation analysis was used to investigate the internal relationship and similarities among the identified metabolites, and seven representative metabolites were selected as "Target-metabolites". Multi-batch urine of samples of heroin abusers were certified based on the UPLC-MS/MS method for further validation of the practicability of using this method for routine analysis. Overall, the target-metabolites can be utilized as assistant "biomarkers" in workplace or mandatory drug screenings. This approach encourages further studies on the development of the "false-positive" identification system.

Topics: Chromatography, High Pressure Liquid; Data Mining; Female; Heroin; Heroin Dependence; Humans; Male; Mass Spectrometry; Morphine Derivatives; Reproducibility of Results; Substance Abuse Detection

Previous imaging studies on heroin addiction have reported brain morphological alterations. However, the effects of heroin exposure on gray matter volume varied among different studies due to different factors such as substitution treatment or mandatory abstinence. Meanwhile, the relationship between gray matter and heroin use history remains unknown. Thirty-three male heroin-dependent (HD) individuals who are not under any substitution treatment or mandatory abstinence and 40 male healthy controls (HC) were included in this structural magnetic resonance imaging study. With an atlas-based approach, gray matter structures up to individual functional area were delineated, and the differences in their volumes between the HD and HC groups were analyzed. In addition, the relationship between gray matter volume and duration of heroin use was explored. The HD group demonstrated significantly lower cortical volume mainly in the prefrontal cortex and mesolimbic dopaminergic regions across different parcellation levels, whereas several visual and somatosensory cortical regions in the HD group had greater volume relative to the HC group at a more detailed parcellation level. The duration of heroin use was negatively correlated with the gray matter volume of prefrontal cortex. These findings suggest that heroin addiction be related to gray matter alteration and might be related to damage/maladaption of the inhibitory control, reward, visual, and somatosensory functions of the brain, although cognitive correlates are warranted in future study. In addition, the atlas-based morphology analysis is a potential tool to help researchers search biomarkers of heroin addiction.

Topics: Brain; Gray Matter; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Prefrontal Cortex

Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence.. A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions.. We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence.. Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.

Topics: Adult; Dopamine; Euphoria; Female; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Heroin; Heroin Dependence; Humans; Male; Memory; Methadone; Phenotype; Polymorphism, Single Nucleotide

Opioid prescribing guidelines recommend reducing or discontinuing opioids for chronic pain if harms of opioid treatment outweigh benefits. As opioid discontinuation becomes more prevalent, it is important to understand whether opioid discontinuation is associated with heroin use. In this study, we sought to assess the association between opioid discontinuation and heroin use documented in the medical record.. A matched nested case-control study was conducted in an integrated health plan and delivery system in Colorado. Patients receiving opioid therapy in the study period (January 2006-June 2018) were included. Opioid discontinuation was defined as ≥45 days with no opioids dispensed after initiating opioid therapy. The heroin use onset date represented the index date. Case patients were matched to up to 20 randomly selected patients without heroin use (control patients) by age, sex, calendar time, and time between initiating opioid therapy and the index date. Conditional logistic regression models estimated matched odds ratios (mOR) for the association between an opioid discontinuation prior to the index date and heroin use.. Among 22,962 patients prescribed opioid therapy, 125 patients (0.54%) used heroin after initiating opioid therapy, of which 74 met criteria for inclusion in the analysis. The odds of opioid discontinuation were approximately two times higher in case patients (n = 74) than control patients (n = 1045; mOR = 2.19; 95% CI 1.27-3.78).. Among patients prescribed chronic opioid therapy, the observed increased risk for heroin use associated with opioid discontinuation should be balanced with potential benefits.

Topics: Adult; Aged; Analgesics, Opioid; Case-Control Studies; Chronic Pain; Cohort Studies; Colorado; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Risk Factors; Withholding Treatment

The current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches. Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls. Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase FYN as the most affected region in neurons. FYN expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro. Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents. Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder.

Topics: Animals; Base Sequence; Behavior, Animal; Chromatin; Corpus Striatum; Cues; Genome; HEK293 Cells; Heroin; Heroin Dependence; Humans; Male; Molecular Targeted Therapy; Neurons; Phosphorylation; Promoter Regions, Genetic; Proto-Oncogene Proteins c-fyn; Rats, Long-Evans; Self Administration; tau Proteins; Transcription, Genetic

Psychiatric comorbidities are frequent among people who inject drugs, they are associated with a poorer prognosis and need to be addressed. Their interaction with daily heroin injection requires clarification.. A cross-sectional survey was conducted among PWID recruited in the city of Haiphong, Vietnam, by respondent-driven sampling. The inclusion criteria were age 18 or older and current injection drug use, verified by skin marks and positive urine tests for heroin or methamphetamine. Data on socio-demographic characteristics, drug use, sexual behaviour and access to treatment were collected using face-to-face questionnaires by trained interviewers. PWID were screened by trained psychiatrists for depression, psychotic disorder and suicidality, using the MINI questionnaire.. 418 participants were included in the analyses. All were injected heroin users, 21 % were diagnosed with a current major depressive disorder, 15 % with a current psychotic disorder and 12 % presented a suicide risk. In the bivariate analyses, regular meth use, cannabis use and ketamine use were positively associated with presenting at least one psychiatric condition while daily heroin injection and being currently treated with methadone were negatively associated. In the multivariate model, poly-substance use was positively associated with depression (methamphetamine and drinking in addition to heroin) and psychotic disorder (methamphetamine and/or hazardous drinking in addition to heroin) while daily heroin injection and current methadone treatment were negatively and independently associated with depression and psychotic syndrome.. Our survey confirms the burden of methamphetamine use and the protective effect of methadone but also a possible protective effect of daily heroin injection.

Topics: Adult; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Male; Mental Disorders; Middle Aged; Substance Abuse, Intravenous; Surveys and Questionnaires; Vietnam

In the context of the current US opioid crisis and the compelling fact that a quarter to a third of all those addicted to heroin pass through its prisons and jails each year, the care of incarcerated opioid-using individuals (OUI) needs to be improved.. Little has been published on the effectiveness or outcomes of heroin-assisted treatment (HAT), a treatment option for severely dependent OUI delivered in a prison setting. The aim of this study was therefore to evaluate such treatment since its implementation. The primary objective was to investigate whether heroin-assisted treatment was associated with severe detrimental health outcomes. The secondary objective was to compare the heroin-assisted treatment group with the general prison population in terms of occupational functioning.. Retrospective cohort study SETTING: An open prison with 120 places SUBJECTS: Data on 1885 male prisoners with a total of 2239 imprisonment periods between 2000 and 2015 was available. Ninety-seven inmates in heroin-assisted treatment were compared with 1788 inmates from the general prison population (reference group).. Mortality, medical complications (including overdoses), and work performance (days worked, sick days, and monthly wages earned).. Inmates receiving HAT were on average 1 year younger (33.8 vs. 34.9 years), had longer prison stays (7.3 vs. 3.0 months), were more often of Swiss nationality (68.0% vs. 28.9%), and had committed more drug- and property-related offenses (49.5% vs. 23.2% and 63.9% vs. 38.3%, respectively) compared to the reference group. No serious heroin-related medical complication occurred during the 15-year window of observation among inmates with heroin-assisted treatment. Their work performance was comparable to that of the reference group.. This study shows that heroin-assisted treatment can be a valuable treatment option for severely dependent OUI during imprisonment, can be delivered safely by prison health staff over extended periods of time, and allows OUI in treatment to achieve work performance rates comparable to that of the general prison population.

Topics: Adult; Buprenorphine; Heroin; Heroin Dependence; Humans; Male; Prisoners; Prisons; Program Evaluation; Retrospective Studies; Switzerland; Treatment Outcome; Work Performance

Drug addiction is a chronic disorder that is characterized by compulsive drug seeking and involves cycling between periods of compulsive drug use, abstinence, and relapse. In both human addicts and animal models of addiction, chronic food restriction has been shown to increase rates of relapse. Previously, our laboratory has demonstrated a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated rats. To date, the neural mechanisms that mediate the effect of chronic food restriction on drug seeking have not been elucidated. However, the paraventricular nucleus of the thalamus (PVT) appears to be a promising target to investigate. The objective of the current study was to examine the role of the PVT in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 days. Rats were then removed from the training chambers and experienced a 14-day withdrawal period with either unrestricted (sated) or mildly restricted (FDR) access to food. On day 14, rats underwent a 1-hour heroin-seeking test under extinction conditions, during which neural activity in the PVT was either inhibited or increased using pharmacological or chemogenetic approaches. Unexpectedly, inhibition of the PVT did not alter heroin seeking in food-restricted or sated rats, while enhancing neural activity in the PVT-attenuated heroin seeking in food-restricted rats. These results indicate that PVT activity can modulate heroin seeking induced by chronic food restriction.

Topics: Animals; Behavior, Animal; Disease Models, Animal; Food Deprivation; Heroin; Heroin Dependence; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Long-Evans

Heroin abuse is a serious problem that endangers human health and affects social stability. Though often being used as confirmation of heroin use, 6-monoacetylmorphine (6-MAM) has limitations due to its short detection window. To compare the detection windows of heroin metabolites (morphine (MOR), 6-MAM, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G)) in human urine, an automated online solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated. The limits of detections (LODs) of the four metabolites were in the range of 1.25-5 ng/mL. Intra and inter-day precision for all the metabolites was 0.4-6.7% and 1.8-7.3%, respectively. Accuracy ranged from 92.9 to 101.7%. This method was then applied to the analysis of urine samples of 20 male heroin abusers. M3G was detected 9-11 days after admission to the drug rehabilitation institute in 40% of heroin users while MOR or M6G was not always detected. The detection window of M3G was thus the longest. Furthermore, M3G had a much higher concentration than MOR and M6G. Therefore, M3G could provide diagnostic information with regard to heroin exposure in the combination with other clues (e.g., heroin seizures at the scene).

Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Heroin; Heroin Dependence; Humans; Limit of Detection; Morphine Derivatives; Solid Phase Extraction; Substance Abuse Detection; Tandem Mass Spectrometry

Dopamine D1 receptors (encoded by DRD1) are implicated in drug addiction and high-risk behaviors. Delay discounting (DD) procedures measure decisional balance between choosing smaller/sooner rewards vs larger/later rewards. Individuals with higher DD (rapid discounting) are prone to maladaptive behaviors that provide immediate reinforcement (eg, substance use). DRD1 variants have been linked with increased DD (in healthy volunteers) and opioid abuse. This study determined whether four dopaminergic functional variants modulated heroin DD and impulsivity.. Substance use, DD, and genotype data (DRD1 rs686 and rs5326, DRD3 rs6280, COMT rs4680) were obtained from 106 current heroin users. Subjects completed an array of DD choices during two imagined conditions: heroin satiation and withdrawal. Rewards were expressed as $10 heroin bag units, with maximum delayed amount of 30 bags. Delays progressively increased from 3 to 96 hours.. DRD1 rs686 (A/A, n = 25; G/A, n = 56; G/G, n = 25) was linearly related to the difference in heroin DD (area under the curve; AUC) between the heroin satiation and withdrawal conditions; specifically, G/G homozygotes had a significantly smaller (satiation minus withdrawal) AUC difference score had higher drug-use impulsivity questionnaire scores, relative to A/A homozygotes, with G/A intermediate. DRD3 and COMT variants were not associated with these DD and impulsivity outcomes.. DRD1 rs686 modulated the difference in heroin DD score between pharmacological states and was associated with drug-use impulsivity. These data support a role of DRD1 in opioid DD and impulsive behaviors.

Topics: Adult; Black or African American; Catechol O-Methyltransferase; Delay Discounting; Female; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Male; Middle Aged; Receptors, Dopamine D1; Receptors, Dopamine D3; Substance Abuse, Intravenous; White People

Postretrieval extinction procedures are effective nonpharmacological interventions for disrupting drug-associated memories. Nonetheless, the conditioned stimulus (CS) memory retrieval-extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval-extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1 hour before the extinction sessions decreased the heroin-priming-induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28 days of withdrawal (ie, remote heroin-associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval-extinction procedure on heroin-priming-induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval-extinction procedure resembled the inhibitory effect of UCS retrieval-extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval-extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin-associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug-associated memories.

Topics: Animals; Basolateral Nuclear Complex; Central Amygdaloid Nucleus; Drug-Seeking Behavior; Endocytosis; Extinction, Psychological; Heroin; Heroin Dependence; Male; Memory Consolidation; Narcotics; Rats; Receptors, AMPA; Time Factors

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

Topics: Animals; Behavior, Animal; Brain; Disease Models, Animal; Drug-Seeking Behavior; Electroacupuncture; Extinction, Psychological; Heroin; Heroin Dependence; Locomotion; Male; Narcotic Antagonists; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Recurrence; Self Administration; Signal Transduction

Topics: Drug Overdose; Epidemics; Europe; Heroin; Heroin Dependence; Humans; Illicit Drugs; Opiate Substitution Treatment; Prescription Drugs; Randomized Controlled Trials as Topic; United States

Emerging evidence suggests that non-medical prescription opioid (NMPO) use may be a risk factor for initiating heroin use; however, pathways from PO to heroin use among youth remain underexplored. We sought to examine the association between NMPO use and heroin initiation.. Between September 2005 and June 2017 data were derived from an open prospective cohort of street-involved youth aged 14-28 who use illegal drugs in Vancouver, Canada. The study included 526 youth who had never used non-injection heroin, and 652 youth who had never used injection heroin at baseline. We used Cox proportional hazards regressions to examine the association between NMPO use - in addition to other substance use patterns - and subsequent initiation into non-injection and injection heroin use.. Among those who had never used non-injection heroin at baseline, 133 (25.3%) initiated non-injection heroin use during the study period. Among those who had never injected heroin at baseline, 137 (21.0%) initiated heroin injection during the study period. In multivariable analyses, NMPO use, crack use, and crystal methamphetamine use predicted non-injection heroin initiation (all p < 0.05). In separate multivariable analyses, non-injection heroin and crystal methamphetamine predicted heroin injection initiation (all p < 0.05).. Among street-involved youth in this setting, NMPO use predicted initiation into non-injection heroin use but not initiation into heroin injection. Interestingly, crack cocaine and crystal methamphetamine use were stronger predictors of heroin initiation than NMPO use was, suggesting that stimulant use may carry greater risks for heroin initiation than NMPO use.

Topics: Adolescent; Adult; Canada; Cohort Studies; Female; Follow-Up Studies; Heroin; Heroin Dependence; Homeless Youth; Humans; Longitudinal Studies; Male; Opioid-Related Disorders; Prospective Studies; Risk Factors; Substance Abuse, Intravenous; Surveys and Questionnaires; Young Adult

Prescription drug monitoring programs (PDMP), by reducing access to prescribed opioids (POs), may contribute to a policy environment in which some people with opioid dependence are at increased risk for transitioning from POs to heroin/other illegal opioids. This study examines how PDMP adoption and changes in the characteristics of PDMPs over time contribute to changes in fatal heroin poisoning in counties within states from 2002 to 2016.. Latent transition analysis to classify PDMPs into latent classes (Cooperative, Proactive, and Weak) for each state and year, across three intervals (1999-2004, 2005-2009, 2010-2016). We examined the association between probability of PDMP latent class membership and the rate of county-level heroin poisoning death.. After adjustment for potential county-level confounders and co-occurring policy changes, adoption of a PDMP was significantly associated with increased heroin poisoning rates (22% increase by third year post-adoption). Findings varied by PDMP type. From 2010-2016, states with Cooperative PDMPs (those more likely to share data with other states, to require more frequent reporting, and include more drug schedules) had 19% higher heroin poisoning rates than states with Weak PDMPs (adjusted rate ratio [ARR] = 1.19; 95% CI = 1.14, 1.25). States with Proactive PDMPs (those more likely to report outlying prescribing and dispensing and provide broader access to law enforcement) had 6% lower heroin poisoning rates than states with No/Weak PDMPs (ARR = 0.94; 95% CI = 0.90, 0.98).. There is a consistent, positive association between state PDMP adoption and heroin poisoning mortality. However, this varies by PDMP type, with Proactive PDMPs associated with a small reduction in heroin poisoning deaths. This raises questions about the potential for PDMPs to support efforts to decrease heroin overdose risk, particularly by using proactive alerts to identify patients in need of treatment for opioid use disorder. Future research on mechanisms explaining the reduction in heroin poisonings after enactment of Proactive PDMPs is merited.

Topics: Analgesics, Opioid; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Opioid-Related Disorders; Prescription Drug Misuse; Prescription Drug Monitoring Programs; United States

Individuals with heroin addiction are prone to dysfunctional decision-making. They frequently choose the short-term rewarding option of drug intake despite experiencing long-term negative consequences. Opioid maintenance treatment (OMT) is the most common treatment of heroin addiction.. In this study, 38 individuals in an early stage of abstinence from heroin addiction (ESA-HA individuals) at the end of inpatient detoxification treatment and 41 individuals in long-term OMT were examined. Decision-making was assessed by (I) a modified version of the Iowa Gambling Task (IGT) with drug-related stimuli focusing on decision-making under ambiguity and (II) the Game of Dice Task (GDT) assessing decision-making under objective risk.. OMT-individuals showed significantly better performance in the IGT than the ESA-HA-individuals. They also showed significantly less craving under exposure of drug-related pictures. In the GDT, OMT-individuals showed significantly less risky decision-making than ESA-HA-individuals.. The results suggest that patients receiving OMT show better functional decision-making and lower craving reactions. It could be assumed that the effectiveness of OMT in preventing relapse is linked to better decision-making and lower craving among these patients.

Topics: Adult; Analgesics, Opioid; Craving; Decision Making; Female; Gambling; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Opiate Substitution Treatment; Reward; Secondary Prevention; Temperance

To date, there have been very limited studies regarding the clinical epidemiology of attempted suicide in Chinese individuals with heroin-dependence. The objective of this study was to examine the prevalence and correlates of suicide attempt in Chinese individuals receiving methadone maintenance treatment for heroin dependence. Demographic, clinical, and psychosocial data of 603 methadone-maintained patients with heroin dependence were collected with a standardized self-administered questionnaire. The presence of suicide attempt and antisocial personality disorder was assessed by using a single question and the Mini-International Neuropsychiatric Interview 5.0. The one-month and lifetime prevalence rates of suicide attempt were 9.5% and 34.2%, respectively. In multivariable logistic regression, lifetime suicide attempt was significantly associated with female gender (OR = 2.81), being 20-39 years old (OR = 2.73), an education level of primary school or lower (OR = 2.07), poor economic status (OR = 3.06), injecting heroin before methadone maintenance treatment (OR = 2.92), depressive symptoms (OR = 3.46), anxiety symptoms (OR = 1.88), and antisocial personality disorder (OR = 2.85). Suicide attempt is very prevalent among Chinese individuals receiving methadone maintenance treatment for heroin dependence. Services for patients with heroin dependence in methadone maintenance treatment clinics in China should include psychosocial supports, periodic screening for suicide attempt and other suicidal behaviors and, when needed, psychiatric treatment and crisis intervention.

Topics: Adult; Antisocial Personality Disorder; Anxiety; China; Depressive Disorder, Major; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Opiate Substitution Treatment; Prevalence; Psychiatric Status Rating Scales; Risk Factors; Suicidal Ideation; Suicide, Attempted; Surveys and Questionnaires

Methadone maintenance treatment (MMT) services have been used in China for treatment of heroin dependence. But no study has been conducted to assess the appropriateness of MMT distribution and the potential abuse of methadone in China. This study aims to do that through a nationwide estimation of methadone consumption in China via wastewater-based epidemiology and subsequently compare it with MMT data and level of heroin abuse.. Wastewater samples were collected from 53 wastewater treatment plants in 27 major cities that cover all geographic regions of China. Methadone and pure heroin consumptions were estimated based on influent concentrations of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), morphine and codeine.. Drug residues were detected in most samples. The ratio of EDDP/methadone was around 2 in influents and methadone and EDDP loads were strongly correlated, indicating that they originated from human consumption. Both influent methadone and EDDP loads in Southwest and Northwest China were significantly higher than those in other regions. The highest estimated consumptions of methadone and heroin in China were 22.0 ± 2.1 mg/1000 in./d and 263.9 ± 115.9 mg/1000 in./d, respectively. There was a significant positive correlation between methadone and heroin consumptions.. Consumption of methadone in China was primarily from MMT services. The use of methadone and heroin displayed a clear geographical pattern: it is higher in the western inland regions than in the eastern regions. This study has shown that the distribution of MMT services is reflective of the level of heroin abuse in different regions of China.

Topics: Adult; Analgesics, Opioid; China; Cities; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Opiate Substitution Treatment; Wastewater; Wastewater-Based Epidemiological Monitoring

Forensic pathologists are requested to select matrices alternative to blood in cases of toxicological interest in which blood is not available for different reasons. We evaluated morphine concentrations in blood, bile, and liver samples in 52 cases of heroin overdoses, relating them to each other, to understand the information that could be derived from their analysis. Gas chromatography/mass spectrometry analysis was performed for all the samples positive on screening for opiates. Shapiro-Wilk test, nonparametric Mann-Whitney test, linear regression analysis, and Bland-Altman test were used for analysis. Linear regression demonstrated that there was not a statistically significant association in morphine concentrations between blood and bile and blood and liver. Mean liver/blood ratio was 2.76, varying from 0.131 to 13.379, and bile/blood ratio was 28.79, varying from 0.28 to 559.16. According to these results, bile analysis is a "screening test"; biliary or hepatic concentration of morphine cannot provide information on hematic concentration at the time of death, having no forensic value taken individually.

Topics: Adolescent; Adult; Bile; Drug Overdose; Female; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Linear Models; Liver; Male; Morphine; Substance Abuse Detection; Young Adult

Opioid misuse and deaths are increasing in the United States. In 2017, Ohio had the second highest overdose rates in the US, with the city of Cincinnati experiencing a 50% rise in opioid overdoses since 2015. Understanding the temporal and geographic variation in overdose emergencies may help guide public policy responses to the opioid epidemic.. We used a publicly available data set of suspected heroin-related emergency calls (n = 6,246) to map overdose incidents to 280 census block groups in Cincinnati between August 1, 2015, and January 30, 2019. We used a Bayesian space-time Poisson regression model to examine the relationship between demographic and environmental characteristics and the number of calls within block groups. Higher numbers of heroin-related incidents were found to be associated with features of the built environment, including the proportion of parks (relative risk [RR] = 2.233; 95% credible interval [CI]: [1.075-4.643]), commercial (RR = 13.200; 95% CI: [4.584-38.169]), manufacturing (RR = 4.775; 95% CI: [1.958-11.683]), and downtown development zones (RR = 11.362; 95% CI: [3.796-34.015]). The number of suspected heroin-related emergency calls was also positively associated with the proportion of male population, the population aged 35-49 years, and distance to pharmacies and was negatively associated with the proportion aged 18-24 years, the proportion of the population with a bachelor's degree or higher, median household income, the number of fast food restaurants, distance to hospitals, and distance to opioid treatment programs. Significant spatial and temporal heterogeneity in the risks of incidents remained after adjusting for covariates. Limitations of this study include lack of information about the nature of incidents after dispatch, which may differ from the initial classification of being related to heroin, and lack of information on local policy changes and interventions.. We identified areas with high numbers of reported heroin-related incidents and features of the built environment and demographic characteristics that are associated with these events in the city of Cincinnati. Publicly available information about opiate overdoses, combined with data on spatiotemporal risk factors, may help municipalities plan, implement, and target harm-reduction measures. In the US, more work is necessary to improve data availability in other cities and states and the compatibility of data from different sources in order to adequately measure and monitor the risk of overdose and inform health policies.

Topics: Bayes Theorem; Databases, Factual; Drug Overdose; Emergency Medical Services; Emergency Service, Hospital; Female; Heroin; Heroin Dependence; Humans; Male; Ohio; Risk Factors; Spatio-Temporal Analysis; Substance-Related Disorders; United States

On a national level, heroin-related hospital admissions have reached an all-time high. With the foot being the fourth most common injection site, heroin-related lower-extremity infections have become more prevalent owing to many factors, including drug preparation, injection practices, and unknown additives.. We present a 16-month case series in which eight patients with lower-extremity infections secondary to heroin abuse presented to The Jewish Hospital in Cincinnati, Ohio.. Three cases of osteomyelitis were seen. All of the infections were cultured and yielded a wide array of microbes, including. This case series brings to light many considerations in the diagnosis and management of the heroin user, including multivariable attenuation of immunity, existing predisposition to infection backed by unsterile drug preparation and injection practices, innocuous presentation of deep infections, microbial spectrum, and recommendations on antimicrobial intervention, noncompliance, and poor follow-up. By having greater knowledge in unique considerations of diagnosis and treatment, more efficient care can be provided to this unique patient population.

Topics: Adult; Anti-Bacterial Agents; Female; Heroin; Heroin Dependence; Humans; Hyperalgesia; Lower Extremity; Magnetic Resonance Imaging; Male; Middle Aged; Osteomyelitis; Pain Management; Patient Compliance; Radiography; Soft Tissue Infections; Substance Abuse, Intravenous

Using mathematical modeling to illustrate and predict how different heroin source-forms: "black tar" (BTH) and powder heroin (PH) can affect HIV transmission in the context of contrasting injecting practices. By quantifying HIV risk by these two heroin source-types we show how each affects the incidence and prevalence of HIV over time. From 1997 to 2010 PH reaching the United States was manufactured overwhelmingly by Colombian suppliers and distributed in the eastern states of the United States. Recently Mexican cartels that supply the western U.S. states have started to produce PH too, replacing Colombian distribution to the east. This raises the possibility that BTH in the western U.S. may be replaced by PH in the future.. We used an agent-based model to evaluate the impact of use of different heroin formulations in high- and low-risk populations of persons who inject drugs (PWID) who use different types of syringes (high vs. low dead space) and injecting practices. We obtained model parameters from peer-reviewed publications and ethnographic research.. Heating of BTH, additional syringe rinsing, and subcutaneous injection can substantially decrease the risk of HIV transmission. Simulation analysis shows that HIV transmission risk may be strongly affected by the type of heroin used. We reproduced historic differences in HIV prevalence and incidence. The protective effect of BTH is much stronger in high-risk compared with low-risk populations. Simulation of future outbreaks show that when PH replaces BTH we expect a long-term overall increase in HIV prevalence. In a population of PWID with mixed low- and high-risk clusters we find that local HIV outbreaks can occur even when the overall prevalence and incidence are low. The results are dependent on evidence-supported assumptions.. The results support harm-reduction measures focused on a reduction in syringe sharing and promoting protective measures of syringe rinsing and drug solution heating.

Topics: Harm Reduction; Heroin; Heroin Dependence; HIV Infections; Humans; Incidence; Models, Theoretical; Needle Sharing; Prevalence; Risk Factors; Risk-Taking; Substance Abuse, Intravenous; Syringes; United States; Viral Load

Polydrug use involving heroin and benzodiazepines is common. The potential risk of additive pharmacological effects may be associated with poorer outcomes in patients who use benzodiazepines together with heroin. The aim of this study was to determine the clinical picture of patients presenting to the emergency department following acute drug toxicity involving heroin and benzodiazepines.. Exposure information, clinical data and outcome of acute drug toxicity presentations were collected between 1 October 2013 and 30 September 2014 as part of the European Drug Emergencies Network (Euro-DEN) project. The database was interrogated to identify patients who had taken heroin with or without benzodiazepine(s).. A total of 1345 presentations involving acute heroin toxicity were identified: 492 had used one or more non-heroin/benzodiazepine drug and were not further considered in this study; 662 were lone heroin users and 191 had co-used heroin with one or more benzodiazepines. Co-users were more likely than lone heroin users to have reduced respiratory rate at presentation 12.7 ± 4.9 vs 13.6 ± 4.4 (p = 0.02) and require admission to hospital 18.3 vs 9.8% (p < 0.01). There were no differences in critical care admission rates 3.1 vs 3.9% (p = 0.83) or length of stay 4 h 59 min vs 5 h 32 min (p = 0.23). The 3 most common benzodiazepines were clonazepam, diazepam, and alprazolam. No differences were observed for clinical features between the three benzodiazepines.. This study shows that co-use of heroin and benzodiazepines is common, although the overall outcomes between co-users of heroin and benzodiazepines and heroin-only users were similar.

Topics: Adolescent; Adult; Benzodiazepines; Critical Care; Emergency Service, Hospital; Europe; Female; Heroin; Heroin Dependence; Hospitalization; Humans; Male; Middle Aged; Prevalence; Respiratory Insufficiency; Risk Assessment; Young Adult

Susceptibility to heroin dependence is strongly influenced by genetic factors with heritability estimates as high as 0.7. A number of genes, as well as environmental factors, are likely to contribute to its etiology. Not all individuals who have ever tried heroin at some stage during their lifetime become dependent on heroin. It has been suggested that genetic factors might be more important in the transition stage to heroin dependence rather than in environmental exposures and experimenting with heroin. As the features of substance dependence and memory formation have been found to be strikingly similar, we have focused on a key enzyme involved in long-term potentiation and synaptic plasticity, namely the calcium-dependent/calmodulin-dependent protein kinase IIα (CAMKIIa). We hypothesized, that CamK2A genetic variation may play a role in the transition from occasional to regular heroin use.. Using quantitative trait association analysis, we addressed this hypothesis by correlating the self-reported time interval between occasional and regular heroin use with the frequency of 12 single nucleotide polymorphisms located within the genomic region of the CamK2A gene. A sample of 570 Caucasian patients was available for analysis.. Single marker association analysis (rs10066581, P=0.007), as well as haplotype analysis (global P=0.005), suggested an association with the quantitative trait 'time interval from occasional to regular heroin use.'. Our results propose that genetic variants located in the genomic region of the CamK2A gene may be involved in transition time from occasional to regular heroin use.

Topics: Adolescent; Adult; Australia; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Case-Control Studies; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Heroin; Heroin Dependence; Humans; Linkage Disequilibrium; Male; Polymorphism, Single Nucleotide; Risk Factors; Young Adult

Toxic leukoencephalopathy is a rare but critical neurological disorder in heroin abusers. Our aim is to compare the clinical manifestations, brain MRIs and prognoses of heroin-induced leukoencephalopathy by different intake routes.. We present two patients with toxic leukoencephalopathy caused by intravenous (IV) injection of heroin and 48 additional cases from systematic reviews of the literature published between 1994 and 2018.. Among the 50 heroin abusers who developed leukoencephalopathy, inhalation was the most popular route (60%), followed by IV injection (30%) and snorting (10%). Mental changes, mutism and urine/fecal incontinence were the major symptoms in patients who IV injected heroin, while cerebellar ataxia and dysarthria were more common among those who inhaled heroin. Delayed-onset encephalopathy uniquely occurred in those who IV injected heroin, whereas progressive encephalopathy was more commonly observed in those who inhaled heroin. Clinical improvement was observed in 60% of patients, the overall mortality rate was 12%, and higher mortality was observed in patients who used the inhalation route (16.7%). The hallmarks on the MRIs of those who inhaled heroin were posterior to anterior involvement of the cerebral white matter and lesions in the posterior limbs of the internal capsules, cerebellum and brainstem. In contrast, those who IV injected heroin had more frequent lesions in the subcortical U fibers and the genu of the internal capsules.. These data could help physicians make an early diagnosis and predict prognosis and suggest that prompt antioxidative or symptomatic treatments might reduce the long-term consequences and mortality of heroin-induced leukoencephalopathy.

Topics: Administration, Inhalation; Administration, Intranasal; Administration, Intravenous; Adult; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Narcotics

Globally, women who use drugs often practice sex work and experience multiple health and social harms that complicate their drug treatment needs. In East Africa, understanding the emergence of heroin use among women is critical in efforts to build effective drug treatment programming, including the ongoing scale-up of medication-assisted treatment (MAT). We explored heroin use among women engaged in sex work in Kenya to inform services.. In a qualitative study of 45 female sex workers reporting substance use in Kisumu, Kenya, 32 reported lifetime heroin use and comprise the focus of this analysis. Semi-structured interviews explored histories of substance use and sex work and health programming needs. Thematic analysis focused on the contexts and meanings of heroin use.. Among 32 women, median age was 28 (range: 18-37). Women commonly smoked cocktails containing heroin while using alcohol and other drugs prior to sex work. Most women perceived heroin to engender "morale" and "courage" to engage in sex work and "fight" potentially abusive clients. Sex work reinforced drug use in ways that both managed and created new risks.. Drawing on the concept of "paradoxical autonomy," we suggest that heroin use engenders new forms of autonomy allowing women to support themselves in conditions of uncertainty, yet does not enable them to entirely overcome their vulnerabilities. Drug treatment programs for sex workers should address the situated logics of substance use in contexts of sexual risk, including patterns of poly-substance use that may render MAT inappropriate for some women who use heroin.

Topics: Adolescent; Adult; Female; Heroin; Heroin Dependence; Humans; Kenya; Qualitative Research; Sex Work; Sex Workers; Substance Abuse, Intravenous; Young Adult

Topics: Biometry; Drug Overdose; Heroin; Heroin Dependence; Humans

Some countries allow physicians to prescribe pharmaceutical-grade diamorphine to dependent users who have previously undergone treatment but are still using street-sourced heroin; this is not allowed in the US. This study provides the first nationally representative US data concerning public support for prescribing diamorphine to dependent users. We also test the hypothesis that calling it "diamorphine" instead of "heroin" increases support for this approach.. The RAND American Life Panel is a nationally representative, probability-based survey of US adults. Of the 3345 panel members invited to take the survey, 2530 (75.6%) provided a valid response to our question module. Respondents were randomly assigned to have the question refer to the prescribed drug as either "heroin" or "diamorphine." The groups did not significantly differ on sex, age, race/ethnicity, or education. We compare the distribution of responses for the two groups and conduct Pearson's chi-squared test with the Rao-Scott correction.. For those asked whether the US should try prescribing pharmaceutical-grade "heroin," the share answering "Yes" (20.8%) was 15 percentage points lower than those responding "No" (35.8%). When the question asked about "diamorphine," the results were nearly reversed: the share answering "Yes" (30.6%) was almost 12 percentage points higher than those responding "No" (18.9%). The distributions of responses were significantly different (p < 0.001).. Support for prescribing diamorphine to dependent users is low in the US. While the results are consistent with the hypothesis that referring to heroin as diamorphine may reduce stigma associated with the substance and increase support for prescribing it, opinions may change as individuals learn they are different names for the same substance.

Topics: Adult; Analgesics, Opioid; Drug Prescriptions; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Surveys and Questionnaires; United States; Young Adult

Topics: Heroin; Heroin Dependence; Humans; Pulmonary Disease, Chronic Obstructive; Smokers; Spirometry

This article examined the differences in causes and health consequences between synthetic drug and heroin abuse in urban China. Two-group comparisons were conducted to quantify differences in individual characteristics, causes of drug use, and HIV/STI risky sexual behavior between synthetic drug and heroin users; logistic regressions were employed to assess the net effect of synthetic drug use on risky sexual behavior. Results revealed that causes of synthetic drug use differed from those of heroin use; a combination of the knowledge gap concerning the harmful impact of synthetic drugs and the lesser punishment for their use appeared a main reason behind the shift from heroin to synthetic drugs; and synthetic drug use was a significant and powerful risk factor for HIV/STI risky sexual behavior. Educational and behavioral interventions are urgently needed to prevent the initiation of synthetic drug use among users to reduce their HIV/STI risky sexual behavior.

Topics: Adult; China; Drug Users; Female; Heroin; Heroin Dependence; HIV Infections; Humans; Logistic Models; Male; Risk Factors; Risk-Taking; Sexual Behavior; Substance-Related Disorders; Synthetic Drugs; Urban Population

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Opioid Epidemic; Smoking; United States

Opioid use disorder is a serious public health issue in the United States. Animal models of opioid dependence are fundamental for studying the etiology of addictive behaviors. We tested the hypothesis that extended access to heroin self-administration leads to increases in heroin intake and produces somatic signs of opioid dependence in both male and female mice. Adult C57BL/6J mice were trained to nosepoke (fixed-ratio 1) to obtain intravenous heroin in six daily 1-h sessions (30-60 μg/kg/infusion). The mice were divided into short access (ShA; 1 h) and long access (LgA; 6 h) groups. Immediately after the 10th escalation session, the mice received a challenge dose of naloxone (1 mg/kg), and somatic signs of withdrawal were recorded. The mice readily acquired intravenous heroin self-administration. LgA mice escalated their drug intake in the first hour across sessions and had significantly higher scores of somatic signs of naloxone-precipitated opioid withdrawal compared with ShA mice. Female mice exhibited increases in heroin intake compared with male mice. Male and female mice exhibited similar levels of somatic signs of withdrawal. Because of the wide availability of genetically modified mouse lines, the present mouse model may be particularly useful for better understanding genetic and sex differences that underlie the transition to compulsive-like opioid taking and seeking.

Topics: Animals; Behavior, Addictive; Behavior, Animal; Female; Heroin; Heroin Dependence; Male; Mice; Narcotics; Rats, Wistar; Self Administration

Detection of heroin use is among the major tasks for drug testing and can be best performed by using 6-acetylmorphine as the target analyte. This study was performed to document analytical findings in oral fluid after OF heroin intake.. The samples were from routine drug testing of patients in substitution treatment. The analytical investigation was made with a forensic accredited liquid chromatography-tandem mass spectrometry method.. Out of 2814 samples, from 1875 patients, sent for routine drug testing, 406 contained one or more opiate in the drug screening when applying a cutoff limit of 1 ng/mL neat OF. Out of these 406, 314 had a measured 6-AM concentration in neat OF ≥ 1 ng/mL. The study demonstrated that 6-AM is a viable parameter in oral fluid drug testing with an about 80% sensitivity compared to using morphine and codeine as biomarkers. An additional value of using 6-AM is the confidence in concluding a heroin intake. The 6-AM concentrations varied between 1 and >1000 ng/mL, with a median value of 18.6 ng/mL. Heroin was measured in 35 samples with a median value of 0.72 ng/mL. The positive rate for opiates in urine and OF drug testing was the same, 13.5%, in similar populations of patients.. 6-AM is a preferred parameter in OF drug testing for monitoring heroin use and makes OF drug testing for detecting heroin use more effective than urine drug testing when using highly sensitive mass spectrometry methods.

Topics: Biomarkers; Chromatography, Liquid; Codeine; Female; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Male; Morphine; Morphine Derivatives; Narcotics; Opiate Substitution Treatment; Saliva; Sensitivity and Specificity; Substance Abuse Detection; Time Factors

Polymorphism of the dopamine D2 receptor TaqIA gene is related to reward response, relapse risks and effect of therapy for drug addiction. Whether the cue-induced craving and brain response was related to dopamine D2 receptor TaqIA gene is unknown.. Forty-nine male heroin-dependent individuals [31 with A1 allele of the TaqIA (A1+), 18 A2 allele carriers (A1-)] under methadone maintenance treatment and 20 healthy control subjects performed a heroin cue-reactivity task during functional magnetic resonance imaging. Cue-elicited craving was measured. Difference in cue induced craving and brain response were analyzed among the three groups. Correlation analyses between craving and differential brain response, heroin use and treatment history were performed within A1+ and A1- group respectively.. Compared with A1- group, A1+ group showed greater cue-induced response in the ventrolateral prefrontal cortex, medial orbitofrontal gyrus, dorsomedial prefrontal cortex, pallidum, putamen, thalamus, superior parietal lobule and superior occipital gyrus. No difference in craving was found. The response in right thalamus positively correlated with daily heroin and methadone dose in A1+ group. For A1- group, response in left ventral orbitofrontal cortex, medial orbitofrontal gyrus, ventral anterior cingulate cortex, caudate, precuneus, calcarine and bilateral pallidum negatively correlated with duration of heroin use. The response in left ventral orbitofrontal cortex, medial orbitofrontal gyrus, bilateral calcarine and right cerebellum negatively correlated with duration of methadone maintenance treatment in A1- group.. The findings supported that A1 allele of the TaqIA is associated with higher salience allocation to heroin-related cues in heroin-dependent patients.

Topics: Adult; Alleles; Analgesics, Opioid; Brain; Craving; Cues; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Pharmacogenomic Variants; Polymorphism, Genetic; Receptors, Dopamine D2; Recurrence; Reward

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Opioid Epidemic; Smoking; United States

Emergency departments (EDs) are experiencing an increasing number of heroin overdose visits. Currently, there is no generally agreed upon ED observation period for heroin overdose patients who receive naloxone.. We aimed to determine the safety of a 2-h observation period for heroin overdose patients who receive naloxone.. We performed a chart review of all patients who presented with any opioid-related complaint between 2009 and 2014 to our urban academic trauma center. Subset analysis of patients with isolated heroin overdose who received naloxone was performed, with the intent of excluding patients intoxicated with long-acting/enteral opioids. The primary outcome was the number of patients who required delayed intervention-specifically, additional naloxone or supplemental oxygen.. Between 2009 and 2014, we recorded 806 visits to our ED for heroin use after receiving naloxone. Twenty-nine patients (3.6%) received a repeat dose of naloxone, and 17 patients (2%) received oxygen ≥2 h after initial naloxone administration. Our 2-h intervention rate was 4.6% (N = 37). This decreased to 1.9% (N = 15) after 3 h and 0.9% (N = 7) after 4 h. Patients with polysubstance use were more likely to receive repeat naloxone (p < 0.01), but not oxygen (p = 0.10). Preexisting cardiopulmonary conditions did not correlate with a need for supplemental oxygen (p = 0.24) or repeat naloxone (p = 0.30).. A 2-h ED observation period for heroin overdose patients reversed with naloxone resulted in a delayed intervention rate of 5%. Clinicians may consider a 3-h observation period, with extra scrutiny in polysubstance abuse.

Topics: Adult; Emergency Service, Hospital; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oxygen; Retrospective Studies; Time Factors; Time-to-Treatment

Heroin addiction is associated with poor oral health. Oral and dental care in heroin addiction might be complicated by altered mental status, negative attitude towards oral health, dental anxiety and fear, drug interaction, and associated medical co-morbidity. We present the oral findings and discuss the dental, behavioural, and anaesthetic management considerations in a 46-year-old man who had dental anxiety and had been an intravenous heroin user for the past 23 years.

Topics: Dental Care; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Oral Health

To describe changes in suspected heroin overdose emergency department (ED) visits.

Topics: Age Factors; Drug Overdose; Emergency Service, Hospital; Heroin; Heroin Dependence; Humans; Rural Population; United States; Urban Population

Sharing of injection drug use paraphernalia is a dyadic process linked to the transmission of HIV and hepatitis C virus (HCV). Despite this, limited research exists identifying specific dyadic interpersonal factors driving injecting partners' engagement in needle/syringe and ancillary injecting equipment sharing among young adults. Using semi-structured in-depth interview data collected between 2014 and 2015 from twenty-seven people who inject drugs (PWID), we applied an inductive approach to identify key injection drug-related interpersonal factors and developed a conceptual model integrating the findings based on interdependence theory. Interactions between injecting partners resulted in varying levels of injecting-related trust, cooperation, intimacy, and power. These factors interacted to collectively influence the type and level of risk perceived and enacted by injecting partners. The relationship between these injecting-related interpersonal factors, on the one hand, and risk perception on the other was dynamic and fluctuated between actions that protect the self (person-centered) and those that protect the partnership (partnership-centered). These findings indicate that the interpersonal context exerts substantial influence that shapes risk perception in all types of injecting partnerships. Partnership-focused prevention strategies should consider the dynamics of trust, cooperation, intimacy, and power, in characterizing dyadic risk perceptions and in understanding risky injecting practices among PWID.

Topics: Adult; Female; Hepacivirus; Hepatitis C; Heroin; Heroin Dependence; HIV; HIV Infections; Humans; Interpersonal Relations; Male; Needle Sharing; Risk Factors; Risk-Taking; Sexual Behavior; Sexual Partners; Substance Abuse, Intravenous; Trust

Topics: Administration, Intranasal; Heroin; Heroin Dependence; Humans; Male; Midwestern United States; Narcotics; Young Adult

The present phase of the overdose epidemic is characterized by fentanyl-contaminated heroin, particularly in the eastern United States (U.S.). However, there is little research examining how changes in drug potency are affecting urban, racial minority individuals who have been affected by both the "old" epidemic of the 1940s through 1980s, as well as the "new" present day epidemic. A focus on the drug using experiences of racial minorities is needed to avoid perpetuating discriminatory responses to drug use in communities of color, which have characterized past U.S. policies. This qualitative study was conducted from March through June 2018 to examine recent experiences of urban, individuals of color who inject drugs to assess the impact of the current overdose epidemic on this understudied population. Interviews were conducted with 25 people who reported current injection drug use. The interviews were transcribed and analyzed using a general inductive approach to identify major themes. Fifteen of 25 participants reported experiencing a non-fatal overdose in the past two years; eight suspected their overdose was fentanyl-related. Likewise, 15 had ever witnessed someone else overdose at least once. Overdoses that required multiple doses of naloxone were also reported. Participants employed several methods to attempt to detect the presence of fentanyl in their drugs, with varying degrees of success. Carrying naloxone and utilizing trusted drug sellers (often those who also use) were strategies used to minimize risk of overdose. Contaminated heroin and increased risk for overdose was often encountered when trusted sources were unavailable. This population is suffering from high rates of recent overdose. Removal of trusted drug sources from a community may inadvertently increase overdose risk. Ensuring access to harm reduction resources (naloxone, drug testing strips) will remain important for addressing ever-increasing rates of overdose among all populations affected.

Topics: Adult; Aged; Drug Contamination; Drug Overdose; Female; Fentanyl; Heroin; Heroin Dependence; Humans; Interviews as Topic; Male; Middle Aged; Naloxone; Narcotic Antagonists; Racial Groups; Substance Abuse, Intravenous; United States; Urban Population; Young Adult

Fentanyl-adulterated heroin supply chains are increasing risks for fatal overdose in the U.S.. The current study examined the use of overdose risk reduction behaviors among persons seeking treatment for heroin use and whether perceptions about the presence of fentanyl in one's heroin are associated with overdose risk reduction behaviors.. We recruited persons with opioid use disorder entering a managed withdrawal program. We used multiple linear regression to estimate the adjusted associations of participant characteristics and perception of fentanyl exposure with the frequency of engaging in each of five overdose reduction behaviors.. Participants (n = 239; 75.3% male, 81.2% White, 67% injectors) estimated that 69.2% of the heroin they use contains fentanyl, and 94.6% knew that fentanyl increases overdose risk. Approximately 30% of respondents reported usually or always making sure others are around when they use heroin, carrying naloxone, taking "tester" doses of heroin or intentionally using in reduced amounts. While a majority of the sample reported never carrying naloxone or taking tester doses, and 70.2% reported never making sure that others around them carry naloxone, 84.5% had implemented one or more behavior at least rarely. Past month injection drug use was associated with making sure others are around, but perceptions about fentanyl in one's heroin were not associated with use of harm reduction behaviors.. In this sample of people who use heroin, although overdose risk reduction behaviors were not usually used, a majority had tried at least one behavior. That perceived exposure to fentanyl-adulterated heroin was not associated with the use of such behaviors provides important implications for public health education and intervention programming.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Fentanyl; Health Knowledge, Attitudes, Practice; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Risk Reduction Behavior

Drug addiction is a harmful preference for drug use over and at the expense of other non-drug-related activities. We previously identified in the rat orbitofrontal cortex (OFC) a mechanism that influences individual preferences between cocaine use and an alternative action rewarded by a non-drug reward (i.e. sweet water). Here, we sought to test the generality of this mechanism to a different addictive drug, heroin. OFC neuronal activity was recorded while rats responded for heroin or the alternative non-drug reward separately or while they chose between the two. First, we found that heroin-rewarded and sweet water-rewarded actions were encoded by two non-overlapping OFC neuronal populations and that the relative size of the heroin population represented individual drug choices. Second, OFC neurons encoding the preferred action-which was the non-drug action in the large majority of individuals-progressively fired more than non-preferred action-coding neurons 1 second after the onset of choice trials and around 1 second before the preferred action was actually chosen, suggesting a pre-choice neuronal competition for action selection. Together with a previous study on cocaine choice, the present study on heroin choice reveals important commonalities in how OFC neurons encode individual drug choices and preferences across different classes of drugs. It also reveals some drug-specific differences in OFC encoding activity. Notably, the proportion of neurons that non-selectively encode both the drug and the non-drug reward was higher when the drug was heroin (present study) than when it was cocaine (previous study). We will discuss the potential functional significance of these commonalities and differences in OFC neuronal activity across different drugs for understanding drug choice.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Choice Behavior; Conditioning, Psychological; Heroin; Heroin Dependence; Neurons; Prefrontal Cortex; Pyramidal Cells; Rats; Rats, Wistar; Reward; Self Administration

The prelimbic cortex (PL) and infralimbic cortex (IL) play a role in context-induced reinstatement of heroin seeking in an animal model of drug relapse. Both the PL and IL receive direct glutamatergic projections from the ventral CA1 (vCA1), which is also involved in context-induced reinstatement of cocaine and heroin seeking. Here we studied the role of vCA1-PL and vCA1-IL projections in context-induced reinstatement of heroin seeking by using electrophysiological, neuropharmacological, chemogenetic, and molecular methods. We showed that context-induced reinstatement of heroin seeking caused selective activation of the vCA1-IL but not vCA1-PL glutamatergic projections, decreased synaptosomal GluA2 expression in the IL, impaired basal synaptic transmission, and facilitation of long-term depression (LTD) in the vCA1-IL pathway. Additionally, chemogenetic inactivation of the vCA1-IL but not vCA1-PL pathway decreased context-induced reinstatement of heroin seeking. Inactivation of the vCA1-IL pathway also reversed synaptosomal GluA2 downregulation and basal transmission reduction, and blocked LTD induction. Taken together, our results demonstrate a critical role of the vCA1-IL glutamatergic projection in context-induced reinstatement of heroin seeking in a rat model of drug relapse.

Topics: Animals; CA1 Region, Hippocampal; Drug-Seeking Behavior; Glutamic Acid; Heroin; Heroin Dependence; Long-Term Synaptic Depression; Male; Narcotics; Neural Pathways; Random Allocation; Rats, Sprague-Dawley; Receptors, AMPA; Self Administration; Synaptic Transmission; Synaptosomes

A recent Cochrane review of randomised trials identified a lack of evidence for interventions provided to drug-using offenders. We use routine data to address whether contact with treatment services reduces heroin users' likelihood of a future acquisitive offence or drug-related poisoning (DRP) death.. Heroin-users were identified from probation assessments and linked to drug-treatment, mortality and offending records. The study cohort was selected to ensure that the subject was not: in prison, in treatment or had recently left treatment. Subjects were classed as initiators if they attended a triage appointment within two weeks of their assessment; non-initiators otherwise. Initiator and non-initiators were compared over a maximum of one year, with respect to their risk of recorded acquisitive offence or DRP-death. Balance was sought using propensity score matching and missing data were accounted for using multiple imputation.. Nine percent of assessments identified for analysis were classed as initiators. Accounting for observed confounding and missing data, there was a reduction in DRPs associated with initiator assessments, however there was uncertainty around this estimate such that a null-effect could not be ruled out (HR: 0.42, 95% CI 0.17-1.04). There was no evidence of a decrease in the recidivism risk, in fact the analysis showed a small increase (HR: 1.10, 95% CI 1.02-1.18).. For heroin-using offenders, initial contact with treatment services does not appear to reduce the likelihood of a future acquisitive offence.

Topics: Adult; Cause of Death; Crime; Criminals; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; United Kingdom

The Opiate Dosage Adequacy Scale (ODAS) is a clinical tool to individually measure the "adequacy" of opioid doses in patients on maintenance treatment. The aim of this paper is to provide evidence for the validity and reliability of the ODAS in a sample of patients in buprenorphine/naloxone (B/N) maintenance treatment.. Cross-sectional study of a convenience sample of B/N-treated patients (n = 316) from four Autonomous Communities in Spain. Participants completed a battery of instruments to assess the following: buprenorphine dose adequacy; heroin dependence severity; psychological adjustment; and patient-desired adjustment of buprenorphine dose.. Exploratory Factor Analysis identified four factors from the ODAS that together account for 85.4% of the total variance: "Heroin craving and use"; "Overmedication"; "Objective opiate withdrawal symptoms (OWS)" and 'Subjective OWS'. Compared to patients with an "inadequate" B/N dose (ODAS), patients with "adequate" doses had less heroin use in the last week (0.01 vs. 0.40; t = -2.73; p < 0.01, 95% CI: -0.67, -0.10), less severe heroin dependence (2.20 vs. 5.26, t = -5.14, p < 0.001; 95% CI: -4.23, -1.88), less psychological distress (3.00 vs. 6.31, t = -4.37, p < 0.001; 95% CI: -4.80, -1.81), and greater satisfaction with their doses (42.1% vs. 13.6%, χ. These findings support the validity and reliability of the ODAS as a tool to measure and assess buprenorphine dose adequacy in the context of an opioid dependency treatment program.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Reproducibility of Results; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Opiate abuse and addiction have become a worldwide epidemic with great societal and financial burdens, highlighting a critical need to understand the neurobiology of opiate addiction. Although several studies have focused on drug-dependent changes in neurons, the role of glia in opiate addiction remains largely unstudied. RNA sequencing pathway analysis from the prefrontal cortex (PFC) of male rats revealed changes in several genes associated with oligodendrocyte differentiation and maturation following heroin self-administration. Among these genes changed was Sox10, which is regulated, in part, by the chromatin remodeler BRG1/SMARCA4. To directly test the functional role of Sox10 in mediating heroin-induced behavioral plasticity, we selectively overexpressed Sox10 and BRG1 in the PFC. Overexpression of either Sox10 or BRG1 decreased the motivation to obtain heroin infusions in a progressive ratio test without altering the acquisition or maintenance of heroin self-administration. These data demonstrate a critical, and perhaps compensatory, role of Sox10 and BRG1 in oligodendrocytes in regulating the motivation for heroin.

Topics: Animals; DNA Helicases; Drug-Seeking Behavior; Gene Expression Regulation; Heroin; Heroin Dependence; Male; Motivation; Narcotics; Nuclear Proteins; Oligodendrocyte Precursor Cells; Prefrontal Cortex; Rats, Sprague-Dawley; Reward; Self Administration; SOXE Transcription Factors; Transcription Factors

Addiction is a chronic disease characterized by persistent vulnerability to relapse during abstinence. In animal models of addiction, accumulating evidence suggests that exposure to environmental enrichment (EE) during periods of abstinence can have curative effects on addiction and reduce the risks of relapse. However, until present most studies have mainly focused on cocaine. In this study, we investigated whether EE could have beneficial effects on cue-induced seeking for several psychoactive drugs belonging to different pharmacological classes such as methamphetamine (METH), heroin (HER) and nicotine (NIC).. After self-administration training of METH, HER and NIC, rats were housed in enriched (EE) or standard environments (SE) for 21-28 days of forced abstinence and then drug-seeking behavior was assessed in the absence of the drug.. We found that, compared to SE housing, exposure to EE reduced drug seeking behavior for all drugs tested.. These findings suggest that the anti-craving effects of EE are general for a wide variety of drugs and support the hypothesis that environmental stimulation may be a general intervention for attenuating relapse in humans.

Topics: Amphetamine-Related Disorders; Animals; Craving; Cues; Disease Models, Animal; Drug-Seeking Behavior; Environment; Generalization, Psychological; Heroin; Heroin Dependence; Housing, Animal; Male; Methamphetamine; Nicotine; Psychotropic Drugs; Rats, Sprague-Dawley; Self Administration; Tobacco Use Disorder

Rates of both opioid and sedative use and misuse are rising. Comorbid opioid and sedative use is associated with especially severe consequences (e.g., overdose and poor health outcomes). Heroin users report multiple motivations for sedative use, including self-medication. We aimed to understand differences in lifetime substance use characteristics between heroin users with different sedative use histories.. Substance use data were collected from 385 non-treatment seeking heroin users. Subjects were divided into four lifetime sedative-use groups: no use, medical use only, non-medical use only, and mixed medical and non-medical use. We examined patterns of use of various substances of abuse (tobacco, alcohol, marijuana, cocaine, heroin, and sedatives) and individual characteristics associated with each.. Non-medical sedative use (alone or in addition to medical use) was associated with more negative consequences from using all substances. Medical sedative use alone was not related to increased overdose or emergency room visits associated with heroin use. Non-medical sedative use was associated with increases in 15 of the 21 measured heroin consequences and only one of those - health problems - was also associated with medical sedative use.. Concomitant non-medical sedative use and heroin use is associated with significantly greater negative outcomes than those experienced by heroin users who report use of sedatives only as prescribed. Understanding these differences offers insight into risks related to using both substances and may help treatment providers create targeted harm reduction interventions for this population.

Topics: Adolescent; Adult; Analgesics, Opioid; Comorbidity; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Hypnotics and Sedatives; Male; Mental Health; Middle Aged; Self Medication; Substance-Related Disorders; Young Adult

In recent years, drug conjugate vaccines have shown promise as therapeutics for substance use disorder. As a means to improve the efficacy of a heroin conjugate vaccine, we systematically explored 20 vaccine formulations with varying combinations of carrier proteins and adjuvants. In regard to adjuvants, we explored a Toll-like receptor 9 (TLR9) agonist and a TLR3 agonist in the presence of alum. The TLR9 agonist was cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826), while the TLR3 agonist was virus-derived genomic doubled-stranded RNA (dsRNA). The vaccine formulations containing TLR3 or TLR9 agonist alone elicited strong antiheroin antibody titers and blockade of heroin-induced antinociception when formulated with alum; however, a combination of TLR3 and TLR9 adjuvants did not result in improved efficacy. Investigation of month-long stability of the two lead formulations revealed that the TLR9 but not the TLR3 formulation was stable when stored as a lyophilized solid or as a liquid over 30 days. Furthermore, mice immunized with the TLR9 + alum heroin vaccine gained significant protection from lethal heroin doses, suggesting that this vaccine formulation is suitable for mitigating the harmful effects of heroin, even following month-long storage at room temperature.

Topics: Adjuvants, Immunologic; Analgesics, Opioid; Animals; Disease Models, Animal; Drug Overdose; Heroin; Heroin Dependence; Humans; Male; Mice; Oligodeoxyribonucleotides; Toll-Like Receptor 3; Toll-Like Receptor 9; Vaccination; Vaccines, Conjugate

Superoxide dismutase-2 (SOD2, OMIM: 147460) is involved in the detoxification of superoxide anions. The SOD2 mRNA level is down-regulated in cells exposed to morphine. Oxidative stress plays an important role in drug dependency. The rs2758339 (A/C) is located in the vicinity of SP1 and NF-κB transcription element sequences and the rs5746136 (A/G) creates a new glucocorticoid receptor binding site. Taken together, it is hypothesized that these polymorphisms might be associated with the risk of heroin dependency (HD) and the SOD2 expression level.. To investigate the association between the SOD2 polymorphisms and the risk of HD, 442 heroin dependent persons and 799 healthy controls were included. This study also, consisted of 77 healthy students of Shiraz University (Iran) to investigate the association between the SOD2 polymorphisms and the gene expression level.. The AC (OR = 0.72, 95% CI = 0.56-0.93, P = 0.013) and CC (OR = 0.64, 95% CI = 0.45-0.92, P = 0.015) genotypes of the rs2758339 were negatively associated with the risk of HD. The AA genotype of the rs5746136 increased the risk of HD (OR = 1.46, 95% CI = 1.03-2.07, P = 0.031). The AA haplotype was associated with the risk of HD (OR = 1.31, 95% CI = 1.09-1.58, P = 0.004). There was no relationship between the study genotypes (or diplotypes) and the SOD2 expression level.. The rs2758339 and rs5746136 polymorphisms of the SOD2 are associated with the risk of HD but not associated with the SOD2 expression level.

Topics: Adult; Case-Control Studies; Female; Gene Expression Regulation; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Heroin; Heroin Dependence; Humans; Iran; Male; Polymorphism, Single Nucleotide; Risk Factors; RNA, Messenger; Superoxide Dismutase

This study assesses whether genetic variants in stress-related genes are associated with prolonged abstinence from heroin in subjects that are not in long-term methadone treatment.. Frequencies of 117 polymorphisms in 30 genes were compared between subjects with history of heroin addiction, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 923).. SNP rs1500 downstream of CRHBP and an interaction of SNPs rs10482672 (NR3C1) and rs4234955 (NPY1R/NPY5R) were significantly associated with prolonged abstinence without agonist treatment.. This study suggests that variability in stress-related genes may contribute to the ability of certain subjects to remain in prolonged abstinence from heroin, possibly due to higher resilience to stress.

Topics: Carrier Proteins; Female; Genetic Predisposition to Disease; Genotype; Heroin; Heroin Dependence; Humans; Male; Methadone; Opiate Substitution Treatment; Polymorphism, Single Nucleotide; Stress, Psychological

Heroin use is increasing in the US. Heroin use may predispose users towards injection routes of drug administration as compared to other illicit substances.. To explore the relationship between heroin use and drug injection, we compared time from first use to first injection (referred to as time to injection onset by drug [TTIOD]) of heroin, methamphetamine/speed, cocaine, and crack cocaine among people who inject drugs (PWID).. Age of first use and first injection by drug was collected from 776 PWID. Survival analyses were used to determine TTIOD and to examine demographic factors associated with TTIOD. Cox regression analysis was used to determine demographic factors associated with drug-specific injection onset.. The eventual injection onset rate by the drug was 99% for participants who used heroin, 85% for participants who used methamphetamine/speed, 80% for participants who used powder cocaine, and 38% for participants who used crack cocaine. Hazard ratios for injection use within one year of first use by drug were: 1.37 (median survival time [MST] = 0.61 years) for heroin, 0.66 (MST = 1.10 years) for methamphetamine/speed, 0.50 (MST = 2.93 years) for powder cocaine, and 0.12 (MST = 39.59 years) for crack cocaine. Demographic differences in TTIOD were found for each drug. Demographic differences were found for eventual injection by drug for all substances except heroin.. Among PWID, heroin use was associated with a more rapid transition to injection and a higher rate of eventual heroin injection regardless of demographics. More robust, innovative efforts to reduce heroin use and prevent injection initiation are urgently needed.

Topics: Adult; California; Epidemics; Female; Heroin; Heroin Dependence; Humans; Male; Methamphetamine; Middle Aged; Risk Factors; Substance Abuse, Intravenous; Time Factors; Young Adult

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component.

Topics: Acute Disease; Adult; Disease Progression; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Paraplegia; Spinal Cord Diseases

Methadone maintenance treatment (MMT) is highly effective for reducing heroin use and HIV transmission among people who inject opioids. We sought to measure and understand factors associated with continued heroin use, a critical factor affecting treatment outcome among MMT patients in Vietnam.. We collected data from medical charts of a nationally representative sample of patients who were on MMT from May 2008 to December 2013. We selected 10 MMT clinics using probability proportional to size and 50 patients/clinic by systematic random sampling. Concurrent heroin use was defined by self-report/positive urine test recorded in patient charts during month 3, 6, 12, and 24 after MMT initiation. We used multivariable logistic regression to identify factors associated with concurrent heroin use over the first 24 months in treatment.. All clients used heroin at baseline; concurrent heroin use was 55% at month 3; 19%, 14.6% and 15.2% at month 6, 12, and 24, respectively. Having no family emotional/financial support at baseline versus having this support (AOR = 2.03; 95% confidence interval [CI] = 1.17-3.53); using heroin for <15 years versus ≥15 years at baseline (AOR = 1.55; 95% CI = 1.01-2.38); being HIV-infected/not on antiretroviral treatment (ART; AOR = 1.79; 95% CI = 1.07-2.98) or being HIV infected/on ART (AOR = 2.39; 95% CI = 1.61-3.55), versus not being HIV infected; baseline methamphetamine use versus non-use (AOR = 2.68; 95% CI = 1.08-6.65), were associated with increased odds of concurrent heroin use among patients.. The association between concurrent heroin use among MMT patients and lack of family emotional/financial support, highlights the critical importance of these types of support for successful treatment. Association with shorter heroin use history suggests motivational enhancement may reduce concurrent heroin use. Living with HIV, whether on ART or not, is associated with increased concurrent heroin use and suggests safe injection commodities and education, and drug-drug interaction management, are needed for this subgroup. Though few MMT clients reported baseline methamphetamine use, its association with later heroin use suggests the need for effective methamphetamine use interventions.

Topics: Adult; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Retrospective Studies; Risk Factors; Vietnam; Young Adult

Drug dependence and withdrawal syndrome induced by abrupt cessation of opioid administration remain a severe obstacle in the clinical treatment of chronic pain and opioid drug addiction. One of the key symptoms during opioid withdrawal is hyperalgesia. The mechanism of opioid withdrawal-induced hyperalgesia remains unclear. P2X2 and P2X3 receptors, members of P2X receptor subunits, act as the integrator of multiple forms of noxious stimuli and play an important role in nociception transduction of chronic neuropathic and inflammatory pain. The process of P2X2 and P2X3 receptor antagonism inhibits inflammatory hyperalgesia, involving the spinal opioid system. However, the role of P2X receptors involved in opioid withdrawal-induced hyperalgesia has seldom been discussed. To explore the role of P2X2 and P2X3 receptors in the opioid-induced hyperalgesia, heroin self-administration rats were adopted, and the thermal and mechanical nociceptive thresholds were evaluated using the paw withdrawal test after abstinence from heroin for 8 days. In addition, the expressions of P2X2 and P2X3 receptors in dorsal root ganglia were analyzed by immunofluorescence. The results showed that after 8 days of abstinence, heroin self-administration rats showed thermal hyperalgesia and mechanical allodynia. Meanwhile, the expressions of the P2X2 and P2X3 receptors in dorsal root ganglia were increased. These results suggest that upregulation of P2X2 and P2X3 receptors might partially play a role in heroin withdrawal-induced hyperalgesia.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Ganglia, Spinal; Heroin; Heroin Dependence; Hot Temperature; Hyperalgesia; Male; Pain Threshold; Rats, Sprague-Dawley; Receptors, Purinergic P2X2; Receptors, Purinergic P2X3; Self Administration; Substance Withdrawal Syndrome; Touch; Up-Regulation

Internationally, overdose is the primary cause of death among people injecting drugs. However, since 2001, heroin-related overdose deaths in the United States (US) have risen sixfold, paralleled by a rise in the death rate attributed to synthetic opioids, particularly the fentanyls. This paper considers the adaptations some US heroin injectors are making to protect themselves from these risks.. Between 2015 and 2016, a team of ethnographers collected data through semi-structured interviews and observation captured in field notes and video recording of heroin preparation/consumption. Ninety-one current heroin injectors were interviewed (Baltimore, n = 22; Chicago, n = 24; Massachusetts and New Hampshire, n = 36; San Francisco, n = 9). Experience injecting heroin ranged from < 1-47 years. Eight participants, who were exclusively heroin snorters, were also interviewed. Data were analyzed thematically.. Across the study sites, multiple methods of sampling "heroin" were identified, sometimes used in combination, ranging from non-injecting routes (snorting, smoking or tasting a small amount prior to injection) to injecting a partial dose and waiting. Partial injection took different forms: a "slow shot" where the user injected a portion of the solution in the syringe, keeping the needle in the injection site, and continuing or withdrawing the syringe or a "tester shot" where the solution was divided into separate injections. Other techniques included getting feedback from others using heroin of the same batch or observing those with higher tolerance injecting heroin from the same batch before judging how much to inject themselves. Although a minority of those interviewed described using these drug sampling techniques, there is clearly receptivity among some users to protecting themselves by using a variety of methods.. The use of drug sampling as a means of preventing an overdose from injection drug use reduces the quantity absorbed at any one time allowing users to monitor drug strength and titrate their dose accordingly. Given the highly unpredictable potency of the drugs currently being sold as heroin in the US, universal precautions should be adopted more widely. Further research is needed into facilitators and barriers to the uptake of these drug sampling methods.

Topics: Drug Monitoring; Drug Overdose; Female; Harm Reduction; Heroin; Heroin Dependence; Humans; Male; Narcotics; Substance Abuse, Intravenous; Taste; United States

Topics: Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment

Topics: Heroin; Heroin Dependence; Humans; Methadone; Treatment Outcome

Repeated administration of heroin results in the induction of physical dependence, which is characterized as a behavioral state of compulsive drug seeking and a high rate of relapse even after periods of abstinence. However, few studies have been dedicated to characterization of the long-term alterations in heroin-dependent patients (HDPs). Herein, we examined the peripheral blood from 810 HDPs versus 500 healthy controls (HCs) according to the inclusion criteria. Compared with the control group, significant decreases of albumin, triglyceride, and total cholesterol levels were identified in HDPs (P < 0.001) versus HCs coupled with an insignificant decrease in BMI. Meanwhile, RNA-sequencing analyses were performed on blood of 16 long-term HDPs and 25 HCs. The results showed that the TNFα signaling pathway and hematopoiesis related genes were inhibited in HDPs. We further compared the transcriptome data to those of SCA2 and posttraumatic stress disorder patients, identified neurodegenerative diseases related genes were commonly up-regulated in coupled with biological processes "vesicle transport", "mitochondria" and "splicing". Genes in the categories of "protein ubiquitination" were down-regulated indicating potential biochemical alterations shared by all three comparative to their controls. In summary, this is a leading study performing a series of through investigations and using delicate approaches. Results from this study would benefit the study of drug addiction overall and link long-term heroin abuse to neurodegenerative diseases.

Topics: Adult; Behavior, Addictive; Case-Control Studies; Down-Regulation; Drug-Seeking Behavior; Female; Heroin; Heroin Dependence; Humans; Male; Neurodegenerative Diseases; RNA; Self Administration; Signal Transduction; Stress Disorders, Post-Traumatic; Transcriptome; Tumor Necrosis Factor-alpha; Up-Regulation

Animal studies suggest that exposure to either of the two widely used drugs of abuse, heroin or cocaine, causes depletion of the antioxidant, reduced glutathione, a hallmark of oxidative stress, in the brain. However, the relevance of the animal findings to the human is uncertain and clinical trials with the antioxidant GSH precursor n-acetylcysteine have produced mixed results in cocaine dependence.. Our major objective was to compare glutathione levels, determined by an HPLC-coulometric procedure, in autopsied brain of chronic heroin (n = 11) and cocaine users (n = 9), who were positive for the drugs in the brain, to those of matched controls (n = 16). Six brain regions were examined, including caudate, hippocampus, thalamus and frontal, temporal and insular cortices.. In contrast to experimental animal findings, we found no statistically significant difference between mean levels of reduced or oxidized glutathione in the drug user vs. control groups. Moreover, no correlation was found between levels of drugs in the brain and those of glutathione.. Acknowledging the many generic limitations of an autopsied human brain study and the preliminary nature of the findings, our data nevertheless suggest that any oxidative stress caused by heroin or cocaine in chronic users of the drugs might not be sufficient to cause substantial loss of stores of glutathione in the human brain, at least during early withdrawal. These findings, requiring replication, might also have some relevance to future clinical trials employing glutathione supplement therapy as an anti-oxidative strategy in chronic users of the two abused drugs.

Topics: Adult; Antioxidants; Autopsy; Brain; Cocaine; Cocaine-Related Disorders; Female; Glutathione; Heroin; Heroin Dependence; Humans; Male; Oxidative Stress

Environmental factors profoundly affect the addictive potential of drugs of abuse and may also modulate the neuro-anatomical/neuro-chemical impacts of uncontrolled drug use and relapse propensity. This study examined the impact of environmental enrichment on heroin self-administration, addiction-related behaviors, and molecular processes proposed to underlie these behaviors. Male Sprague-Dawley rats in standard and enriched housing conditions intravenously self-administered similar amounts of heroin over 14 days. However, environmental enrichment attenuated progressive ratio, extinction, and reinstatement session responding after 14 days of enforced abstinence. Molecular mechanisms, namely DNA methylation and gene expression, are proposed to underlie abstinence-persistent behaviors. A global reduction in methylation is reported to coincide with addiction, but no differences in total genomic methylation or repeat element methylation were observed in CpG or non-CpG (CH) contexts across the mesolimbic circuitry as assessed by multiple methods including whole genome bisulfite sequencing. Immediate early gene expression associated with drug seeking, taking, and abstinence also were examined. EGR1 and EGR2 were suppressed in mesolimbic regions with heroin-taking and environmental enrichment. Site-specific methylation analysis of EGR1 and EGR2 promoter regions using bisulfite amplicon sequencing (BSAS) revealed hypo-methylation in the EGR2 promoter region and EGR1 intragenic CpG sites with heroin-taking and environmental enrichment that was associated with decreased mRNA expression. Taken together, these findings illuminate the impact of drug taking and environment on the epigenome in a locus and gene-specific manner and highlight the need for positive, alternative rewards in the treatment and prevention of drug addiction.

Topics: Animals; CpG Islands; DNA Methylation; Early Growth Response Protein 1; Early Growth Response Protein 2; Environment; Epigenesis, Genetic; Gene Expression Regulation; Heroin; Heroin Dependence; Housing, Animal; Male; Narcotics; Random Allocation; Rats, Sprague-Dawley; Reinforcement, Psychology; RNA, Messenger; Self Administration

People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date.. A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection.. Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected.. The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID.

Topics: Adult; Analgesics, Opioid; Botulism; Disease Outbreaks; Drug Contamination; Female; Harm Reduction; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Risk Factors; Risk Management; Scotland; Wound Infection; Young Adult

Previously, we reported a marked increase in the use of heroin as an initiating opioid in non-tolerant, first time opioid users. In the current paper, we sought to update and expand upon these results, with a discussion of the policy implications on the overall opioid epidemic.. Opioid initiation data from the original study were updated to include surveys completed through 2017 (N = 8382) from a national sample of treatment-seeking opioid users. In addition, past month abuse of heroin and prescription were analyzed as raw numbers of treatment program entrant in the last five years (2013-2017), drawing from only those treatment centers that participated every year in that time frame.. The updated data confirm and extend the results of our original study: the use of heroin as an initiating opioid increased from 8.7% in 2005 to 31.6% in 2015, with increases in overall Ns per initiation year reflecting a narrowing of the "treatment gap", the time lag between opioid initiation from 2005 to 2015 and later treatment admission (up to 2017). Slight decreases were observed in treatment admissions, but this decline was totally confined to prescription opioid use, with heroin use continuing to increase in absolute numbers.. Given that opioid novices have limited tolerance, the risk of fatal overdose for heroin initiates is elevated compared to prescription opioids, particularly given non-oral administration and often unknown purity/adulterants (i.e., fentanyl). Imprecision of titrating dose among opioid novices may explain observed increases opioid overdoses. Future policy decisions should note that prescription opioid-specific interventions may have little impact on a growing heroin epidemic.

Topics: Adult; Age of Onset; Analgesics, Opioid; Drug Overdose; Drug Tolerance; Health Policy; Heroin; Heroin Dependence; Humans; Opioid-Related Disorders; Substance-Related Disorders

In heroin-related deaths, it is often of interest to determine the approximate time span between intake of heroin and death, and to decide whether heroin or other opioids have been administered. In some autopsy cases, peripheral blood cannot be sampled due to decomposition, injuries or burns. The aim of the present study was to investigate whether measurements of heroin metabolites in matrices other than peripheral blood can be used to differentiate between rapid and delayed heroin deaths, and if morphine/codeine ratios measured in other matrices can separate heroin from codeine intakes.. In this study, we included 51 forensic autopsy cases where morphine was detected in peripheral blood. Samples were collected from peripheral and cardiac blood, pericardial fluid, psoas and lateral vastus muscles, vitreous humor and urine. The opioid analysis included 6-acetylmorphine (6-AM), morphine, morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G) and codeine. Urine was only used for qualitative detection of 6-AM. 45 heroin-intake cases were divided into rapid deaths (n=24), based on the detection of 6-AM in blood, or delayed deaths (n=21), where 6-AM was detected in at least one other matrix but not in blood. An additional 6 cases were classified as codeine-intake cases, based on a morphine/codeine ratio below unity (<1) in peripheral blood, without detecting 6-AM in any matrix.. The median morphine concentrations were significantly higher in the rapid compared with the delayed heroin deaths in all matrices (p=0.004 for vitreous humor and p<0.001 for the other matrices). In the rapid heroin deaths, the M3G/morphine concentration ratios were significantly lower than in the delayed deaths both in peripheral and cardiac blood (p<0.001), as well as in pericardial fluid (p<0.001) and vitreous humor (p=0.006), but not in muscle. The morphine/codeine ratios measured in cardiac blood, pericardial fluid and the two muscle samples resembled the ratios in peripheral blood, although codeine was less often detected in other matrices than peripheral blood.. Measurements of heroin-metabolites in cardiac blood, pericardial fluid and vitreous humor provide information comparable to that of peripheral blood regarding rapid and delayed heroin deaths, e.g. M3G/morphine ratios <2 indicate a rapid death while ratios >3 indicate a delayed death. However, considerable overlap in results from rapid and delayed deaths was observed, and measurements in muscle appeared less useful. Furthermore, matrices other than peripheral blood can be used to investigate morphine/codeine ratios, but vitreous humor seems less suited.

Topics: Codeine; Drug Overdose; Forensic Toxicology; Heroin; Heroin Dependence; Humans; Morphine; Morphine Derivatives; Muscle, Skeletal; Pericardial Fluid; Postmortem Changes; Time Factors; Vitreous Body

The Kreek-McHugh-Schluger-Kellogg (KMSK) scales provide a rapid assessment of maximal self-exposure to specific drugs and can be used as a dimensional instrument. This study provides a re-evaluation of the KMSK scales for cannabis, alcohol, cocaine, and heroin in a relatively large multi-ethnic cohort, and also the first systematic comparison of gender-specific profiles of drug exposure with this scale.. This was an observational study of n = 1,133 consecutively ascertained adult volunteers. The main instruments used were the SCID-I interview (DSM-IV criteria) and KMSK scales for cannabis, alcohol, cocaine, and heroin.. Participants were 852 volunteers (297 female) with specific DSM-IV abuse or dependence diagnoses, and 281 volunteers without any drug diagnoses (154 female). Receiver operating characteristic (ROC) curves were calculated for concurrent validity of KMSK scores with the respective DSM-IV dependence diagnoses. The areas under the ROC curves for men and women combined were 99.5% for heroin, 97% for cocaine, 93% for alcohol, and 85% for cannabis. Newly determined optimal KMSK "cutpoint" scores were identical for men and women for cocaine and heroin dependence diagnoses, but were higher in men than in women, for cannabis and alcohol dependence diagnoses.. This study confirms the scales' effectiveness in performing rapid dimensional analyses for cannabis, alcohol, cocaine, and heroin exposure, in a cohort larger than previously reported, with "cutpoints" changed from initial determinations, based on this larger sample. The KMSK scales also detected gender differences in self-exposure to alcohol and cannabis that are associated with the respective dependence diagnoses.

Topics: Adult; Alcoholism; Cannabis; Cocaine; Cohort Studies; Diagnostic and Statistical Manual of Mental Disorders; Female; Heroin; Heroin Dependence; Humans; Male; Marijuana Abuse; Middle Aged; ROC Curve; Sex Characteristics; Substance-Related Disorders; Young Adult

Heroin use is associated with a disproportionately high level of morbidity and mortality with most deaths attributable to drug overdose. Aggregate heroin purity data has been used to examine the relationship between overdose and variability in street-level heroin, however heroin purity data alone may not be the most appropriate nor a sensitive enough measurement tool for this assessment. The aim of this study was to measure the variability in effective dose of street-level heroin seizures, accounting for variation in both purity and mass, and determine the proportion of samples with higher than expected effective dose that would not be detected using a purity-only measure.. Data on Victorian heroin seizures ≤150mg in mass made between 01/01/2012 and 31/12/2013 were obtained from the Victoria Police Forensic Services Department. The effective dose of heroin in each sample was determined by multiplying the mass and purity variables. Effective dose outlier samples were considered as those containing either greater than 1.5-2 times or >2 times the median effective dose of heroin for the sample data.. The 983 street-level heroin samples of ≤150mg had a median mass of 92mg (IQR of 43mg), a median purity of 13% (range 3.6%-80.9%) and a median effective dose of 12.0mg of heroin (IQR 6.6mg; range 0.4mg-111mg). Approximately one in 13 samples (8%) and one in 17 samples (6%) contained between 1.5-2 times and >2 times the median effective dose of heroin respectively.. The effective dose of heroin is a more appropriate measure than purity to identify outlier samples that containing larger than expected doses of heroin compared to typical doses that may be expected by users. Together with other identified risk factors, fluctuation in the effective dose of heroin contained in street-level samples may contribute to the potential for overdose.

Topics: Drug Contamination; Drug Overdose; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Illicit Drugs; Linear Models

The objective of the study was to describe psychological features of abstinent heroin users undergoing rehabilitation in Saint Petersburg, Russia. Study subjects (n = 197) were recruited prospectively at the time of their admission to rehabilitation between March 2010 and May 2011 at 7 inpatient opiate addiction rehabilitation centers in Saint-Petersburg and neighboring regions, Russia. The centers provided varying rehabilitation programs; 6 of them were religious centers. Socio-demographic information and self-reported HIV status were collected. Personality profiles and severity of drug-associated problems were estimated before and after rehabilitation using the Minnesota Multiphasic Personality Inventory 2 (MMPI-2), and the Addiction Severity Index (ASI).. Thirty-three (17%) subjects dropped out before completing rehabilitation (non-completers). All subjects (completers and non-completers) had psychopathological personality profiles according to MMPI-2. These profiles were refractory to clinically significant improvement after rehabilitation, although some statistically significant changes toward improvement were observed. ASI scores showed statistically and clinically significant improvements after rehabilitation on all scales. Participants in longer-term versus shorter-term rehabilitation programs showed similar changes in their pre- and post-rehabilitation MMPI-2 and ASI scores. Our results suggest that unmet psychiatric needs should be addressed to potentially improve treatment completion in this population.

Topics: Heroin; Heroin Dependence; Humans; MMPI; Personality; Personality Disorders; Russia

Topics: Computer Simulation; Drug Overdose; Drug Tolerance; Drug Users; Drug Utilization; Emergency Service, Hospital; Facilities and Services Utilization; Female; Fentanyl; Heroin; Heroin Dependence; HIV Infections; Humans; Models, Psychological; Naloxone; Opioid-Related Disorders; Prescription Drugs; Rural Population; Social Networking; Unemployment; United States; Video Recording

Drug addiction is a complex disease that is impacted by numerous factors. One such factor, time of day, influences drug intake, but there have been no investigations of how time of day affects the amount of drug taken and the development of addiction-like behavior. Previous data from our group show circadian disruption in rats given access to heroin during the light phase, which is important because circadian disruption, itself, can increase drug intake. Thus, the goal of this experiment was to determine how time of day of access affects heroin self-administration and the development of addiction-like behaviors including escalation of heroin intake, willingness to work for heroin on a progressive ratio schedule of reinforcement, seeking during extinction, incubation of seeking, and reinstatement of heroin-seeking behavior.. Male Sprague Dawley rats were given the opportunity to self-administer heroin for 6 h per trial during the second half of either the light or dark phase for 18 trials, including one progressive ratio challenge. Rats then underwent 14 days of abstinence, with a 5-h extinction test occurring on both the first and the 14th days of abstinence. The second extinction test was followed by a heroin prime and 1 h of reinstatement testing. On the following day, a subset of rats were tested in an additional extinction test where rats were tested either at the same time of the day as their previous self-administration sessions or during the opposite light/dark phase.. Relative to Light Access rats, Dark Access rats took more heroin, exhibited more goal-directed behavior, exhibited more seeking during the dark phase, failed to extinguish seeking during the 5-h extinction test in the dark phase, and exhibited greater incubation of heroin seeking following abstinence. However, Dark Access rats did not escalate drug taking over trials, work harder for drug, or seek more during drug-induced reinstatement than Light Access rats.. These results show that time of access to heroin affects overall heroin intake and seeking in extinction, but does not affect other addiction-like behaviors in rats.

Topics: Animals; Behavior, Addictive; Circadian Rhythm; Disease Models, Animal; Extinction, Psychological; Heroin; Heroin Dependence; Male; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration

Since 2000, heroin use patterns have shifted within the United States. How this change may relate to polydrug use among local heroin users is unknown. Although polydrug use has been studied, user perceptions of drug use in terms of health risks, arrest risk, availability, cost, liking, and dependence have not been considered.. Data are presented from a brief, face-to-face survey conducted in 2016 of 200 non-in-treatment heroin users from Cleveland, OH. We assessed the use of and attitudes on alcohol, marijuana, methamphetamine, heroin, crack cocaine, powder cocaine, and prescription drugs. We estimated polydrug (concurrent past month) use with cluster analysis and latent profiles. Regression analysis estimated the strength of relationships between attitudes and frequency of use.. We identified five clusters: Cluster 1 used heroin concomitantly with alcohol and occasionally crack; Cluster 2 used heroin and crack cocaine daily; Cluster 3 used heroin daily and almost exclusively; Cluster 4 used heroin and marijuana daily; and Cluster 5 were part-time drug users. Drug use frequency was associated with liking and being anxious when drugs could not be obtained. High perceived availability of heroin and cocaine and low cost facilitated polydrug use.. Understanding polydrug use clusters among heroin users is important for addressing the larger opioid epidemic. Users' perceptions of a drug's availability and cost appeared to facilitate polydrug use and justify more detailed future research on drug access.

Topics: Adult; Alcoholism; Amphetamine-Related Disorders; Analgesics, Opioid; Cocaine-Related Disorders; Crack Cocaine; Drug Users; Female; Heroin; Heroin Dependence; Humans; Male; Marijuana Abuse; Middle Aged; Ohio; Self Report; Substance-Related Disorders

Opioid abuse is a rapidly growing public health crisis in the USA. Despite extensive research in the past decades, little is known about the etiology of opioid addiction or the neurobiological risk factors that increase vulnerability to opioid use and abuse. Recent studies suggest that the type 2 metabotropic glutamate receptor (mGluR2) is critically involved in substance abuse and addiction. In the present study, we evaluated whether low-mGluR2 expression may represent a risk factor for the development of opioid abuse and addiction using transgenic mGluR2-knockout (mGluR2-KO) rats. Compared to wild-type controls, mGluR2-KO rats exhibited higher nucleus accumbens (NAc) dopamine (DA) and locomotor responses to heroin, higher heroin self-administration and heroin intake, more potent morphine-induced analgesia and more severe naloxone-precipitated withdrawal symptoms. In contrast, mGluR2-KO rats displayed lower motivation for heroin self-administration under high price progressive-ratio (PR) reinforcement conditions. Taken together, these findings suggest that mGluR2 may play an inhibitory role in opioid action, such that deletion of this receptor results in an increase in brain DA responses to heroin and in acute opioid reward and analgesia. Low-mGluR2 expression in the brain may therefore be a risk factor for the initial development of opioid abuse and addiction.

Topics: Animals; Behavior, Addictive; Gene Deletion; Heroin; Heroin Dependence; Locomotion; Male; Nucleus Accumbens; Rats; Rats, Transgenic; Rats, Wistar; Receptors, Metabotropic Glutamate; Reinforcement Schedule; Self Administration

We sought to describe an emerging drug use pattern characterized by injection of both methamphetamine and heroin. We examined differences in drug injection patterns by demographics, injection behaviors, HIV and HCV status, and overdose.. Persons who inject drugs (PWID) were recruited as part of the National HIV Behavioral Surveillance (NHBS) system in Denver, Colorado. We used chi-square statistics to assess differences between those who reported only heroin injection, only methamphetamine injection, and combined heroin and methamphetamine injection. We used generalized linear models to estimate unadjusted and adjusted prevalence ratios to describe the association between drug injection pattern and reported nonfatal overdose in 2015. We also examined changes in the drug reported as most frequently injected across previous NHBS cycles from 2005, 2009, and 2012.. Of 592 participants who completed the survey in 2015, 173 (29.2%) reported only injecting heroin, 123 (20.8%) reported only injecting methamphetamine, and 296 (50.0%) reported injecting both drugs during the past 12 months. Injecting both heroin and methamphetamine was associated with a 2.8 (95% confidence interval: 1.7, 4.5) fold increase in reported overdose in the past 12 months compared with only injecting heroin. The proportion of those reporting methamphetamine as the most frequently injected drug increased from 2.1% in 2005 to 29.6% in 2015 (p < 0.001).. The rapid increase in methamphetamine injection, and the emergence of combining methamphetamine with heroin, may have serious public health implications.

Topics: Adolescent; Adult; Amphetamine-Related Disorders; Comorbidity; Female; Hepatitis C; Heroin; Heroin Dependence; HIV Infections; Humans; Male; Methamphetamine; Middle Aged; Prevalence; Substance Abuse, Intravenous; Young Adult

Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome.

Topics: ADAM10 Protein; Adult; Amyloid Precursor Protein Secretases; Antigens, CD; Cadherins; Female; Heroin; Heroin Dependence; HIV Infections; Humans; Interleukin-7; Male; Membrane Proteins; Methadone; Morphine; Pharmacogenetics; Polymorphism, Single Nucleotide; Treatment Outcome; Vitamin D

Topics: Heroin; Heroin Dependence; Humans

Topics: Adolescent; Drug Overdose; Epidemics; Heroin; Heroin Dependence; Humans; Naloxone; Opioid-Related Disorders; United States; Young Adult

The effect of heroin administration route on speed of transition to regular use is unknown. This paper aims to determine whether the speed of transition from initiation of heroin use to daily heroin use differs by route of administration (injecting, chasing/inhaling or snorting).. Privileged access interviewer survey of purposively selected sample of 395 current people who use heroin (both in and not in treatment) in London, UK (historical sample from 1991). Data on age and year of initiation, time from initiation to daily use and routes of administration were collected by means of a structured questionnaire. Generalised ordered logistic models were used to test the relationship between route of initial administration of heroin and speed of transition to daily heroin use. Analyses were adjusted for gender, ethnicity, daily use of other drug(s) at time of initiation, year of initiation and treatment status at interview.. After adjustment, participants whose initial administration route was injecting had a 4.71 (95% confidence interval 1.34-16.5) increase in likelihood of progressing to daily use within 1-3 weeks of initiation, compared to those whose initial administration route was non-injecting.. The speed of transition from first use to daily heroin use is faster if the individual injects heroin at initiation of use. Those who initiate heroin use through injecting have a shorter time frame for intervention before drug use escalation. [Hines LA, Lynskey M, Morley KI, Griffiths P, Gossop M, Powis B, Strang J. The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev 2017;00:000-000].

Topics: Age of Onset; Drug Administration Routes; Female; Heroin; Heroin Dependence; Humans; London; Male; Time Factors

This article highlights the experiences of a peer-run group, SALOME/NAOMI Association of Patients (SNAP), that meets weekly in the Downtown Eastside of Vancouver, British Columbia, Canada. SNAP is a unique independent peer- run drug user group that formed in 2011 following Canada's first heroin-assisted treatment trial (HAT), North America Opiate Medication Initiative (NAOMI). SNAP's members are now made up of former research participants who participated in two heroin-assisted trials in Vancouver. This article highlights SNAP members' experiences as research subjects in Canada's second clinical trial conducted in Vancouver, Study to Assess Longer-term Opioid Medication Effectiveness (SALOME), that began recruitment of research participants in 2011.. This paper draws on one brainstorming session, three focus groups, and field notes, with the SALOME/NAOMI Association of Patients (SNAP) in late 2013 about their experiences as research subjects in Canada's second clinical trial, SALOME in the DTES of Vancouver, and fieldwork from a 6-year period (March 2011 to February 2017) with SNAP members. SNAP's research draws on research principles developed by drug user groups and critical methodological frameworks on community-based research for social justice.. The results illuminate how participating in the SALOME clinical trial impacted the lives of SNAP members. In addition, the findings reveal how SNAP member's advocacy for HAT impacts the group in positive ways. Seven major themes emerged from the analysis of the brainstorming and focus groups: life prior to SALOME, the clinic setting and routine, stability, 6-month transition, support, exiting the trial and ethics, and collective action, including their participation in a constitutional challenge in the Supreme Court of BC to continue receiving HAT once the SALOME trial ended.. HAT benefits SNAP members. They argue that permanent HAT programs should be established in Canada because they are an effective harm reduction initiative, one that also reduces opioid overdose deaths.

Topics: British Columbia; Clinical Trials as Topic; Drug Overdose; Focus Groups; Harm Reduction; Heroin; Heroin Dependence; Humans; Narcotics; Needle-Exchange Programs; Parents; Social Justice; Treatment Outcome

To evaluate regulation of the endoplasmic reticulum stress (ERS) response by acupuncture and to investigate its neuroprotective effect on brain injury caused by heroin addiction.. A total of 48 male Sprague-Dawley rats were randomly divided into a healthy control group (Control), an untreated heroin exposed group (Heroin) and a heroin exposed group receiving electroacupuncture (EA) treatment at GV14 and GV20 (Heroin+acupuncture) with n=16 rats per group. A rat model of heroin addiction was established by intramuscular injection of incremental doses of heroin for 8 consecutive days. A rat model of heroin relapse was established according to the exposure (addiction) → detoxification method. Apoptotic changes in nerve cells in the hippocampus and ventral tegmental area (VTA) were evaluated in each group of rats using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. PERK, eIF2a, CHOP, IRE1 and JNK gene expression and protein expression were measured using quantitative real-time PCR (RT-qPCR) assay and immunohistochemical assay, respectively.. The total number of positive nerve cells in the hippocampus and VTA was significantly lower in the Heroin+acupuncture group than in the Heroin group (p<0.01). Compared with the Heroin group, mRNA and protein expression of PERK, eIF2a, CHOP, IRE1 and JNK in the hippocampus and VTA were significantly downregulated in the Heroin+acupuncture group (p<0.05).. The acupuncture-regulated ERS response appears to mediate the neuroprotective effect of acupuncture in heroin-addicted rats with brain injury. Inhibition of CHOP and JNK upregulation and reduction of nerve cell apoptosis may be the main mechanisms underlying the effects of acupuncture on heroin addiction-induced brain injury.

Topics: Acupuncture Therapy; Animals; Apoptosis; Brain; Brain Injuries; Disease Models, Animal; Electroacupuncture; Endoplasmic Reticulum Stress; Heroin; Heroin Dependence; JNK Mitogen-Activated Protein Kinases; Male; Neuroprotective Agents; Rats, Sprague-Dawley; Transcription Factor CHOP

Illicit fentanyl use has become wide spread in the US, causing high rates of overdose deaths among people who use drugs. This study describes patterns and perceptions of fentanyl exposure among opioid users in Rhode Island.. A mixed methods study was conducted via questionnaire with a convenience sample of 149 individuals using illicit opioids or misusing prescription opioids in Rhode Island between January and November 2016. Of these, 121 knew of fentanyl and reported known or suspected exposure to fentanyl in the past year. Semi-structured interviews were conducted with the first 47 participants.. Study participants were predominantly male (64%) and white (61%). Demographic variables were similar across sample strata. Heroin was the most frequently reported drug of choice (72%). Self-reported exposure to illicit fentanyl in the past year was common (50.4%, n=61). In multivariate models, regular (at least weekly) heroin use was independently associated with known or suspected fentanyl exposure in the past year (adjusted prevalence ratio (APR)=4.07, 95% CI: 1.24-13.3, p=0.020). In interviews, users described fentanyl as unpleasant, potentially deadly, and to be avoided. Participants reporting fentanyl exposure routinely experienced or encountered non-fatal overdose. Heroin users reported limited ability to identify fentanyl in their drugs. Harm reduction strategies used to protect themselves from fentanyl exposure and overdose, included test hits, seeking prescription opioids in lieu of heroin, and seeking treatment with combination buprenorphine/naloxone. Participants were often unsuccessful in accessing structured treatment programs.. Among illicit opioid users in Rhode Island, known or suspected fentanyl exposure is common, yet demand for fentanyl is low. Fentanyl-contaminated drugs are generating user interest in effective risk mitigation strategies, including treatment. Responses to the fentanyl epidemic should be informed by the perceptions and experiences of local users. The rapid scale-up of buprenorphine/naloxone provision may slow the rate of fentanyl-involved overdose deaths.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Drug Contamination; Drug Overdose; Female; Fentanyl; Harm Reduction; Heroin; Heroin Dependence; Humans; Illicit Drugs; Interviews as Topic; Male; Middle Aged; Prevalence; Rhode Island; Risk; Surveys and Questionnaires; Young Adult

This study aimed to explore the bidirectional relationships between retention and health-related quality of life (HRQoL) in patients from mainland China receiving methadone maintenance treatment (MMT). This prospective cohort study recruited 1,212 eligible MMT patients from the two largest MMT clinics (one privately and another publicly funded) in Xi'an. This study started in March 2012 with a 2-year follow-up until March 2014. Retention was assessed by repeated terminations, past treatment duration, premature terminations, and follow-up treatment duration. HRQoL was evaluated using the Chinese (simple) short-form 36 health survey version 2 (SF-36v2) and the quality of life scale for drug addicts (QOL-DAv2.0). Linear and Cox regression analyses were used to explore relationships between retention and HRQoL. A general linear model was used to further examine the global effect of past treatment duration on HRQoL. Multivariate analyses showed that repeated terminations had no significant impact on HRQoL scores in MMT patients; however, past treatment time (year) influenced the SF-36v2PCS (P = 0.004): treatment for ≥4 years showed a lower SF-36v2PCS score (regression coefficient: -2.39; 95% confidence interval [CI]: -3.80, -0.97; P = 0.001) than treatment for <1 year. In addition, patients with an SF-36v2PCS score > 49 (hazard ratio: 0.83; 95% CI: 0.69, 0.98; P = 0.03) were 17% less likely to terminate MMT than those with scores of ≤49. In conclusion, retention and HRQoL tended to have a bidirectional relationship, which should be considered in the development of retention and health-management programs for patients with MMT.

Topics: Adolescent; Adult; Aged; Child; China; Drug Users; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Multivariate Analysis; Opiate Substitution Treatment; Proportional Hazards Models; Quality of Life; Substance Abuse Treatment Centers; Young Adult

Black tar heroin is typically prepared for injection with heat which decreases the risk of HIV transmission by inactivating the virus. We received reports that persons who inject drugs (PWID) in Tijuana, Baja California, Mexico, a black tar heroin market, were using only water to dissolve heroin.. Because Tijuana abuts San Diego County, CA, United States, we undertook the present analyses to determine the prevalence of this practice among PWID in San Diego, California.. PWID completed quarterly behavioral assessments and serological testing for blood-borne viruses. Bivariate and multivariable logistic regression models were constructed to assess for individual, social, and structural correlates of preparing heroin without heat within the preceding 6 months.. Nearly half of black tar heroin users (149/305) reported they had prepared heroin without heat within 6 months. In multivariable analysis, cold preparation was independently associated with younger age (10 year decrease; AOR = 1.25; 95% CI 1.03, 1.53), more drug injecting acquaintances (per 5 acquaintance increase; AOR = 1.05; 95% CI 1.01, 1.09) and prefilled syringe use (injecting drugs from syringes that are already filled with drugs before purchase; AOR = 1.86; 95% CI 1.14, 3.02). Conclusions/Importance: To our knowledge, this is the first paper to report that PWID living in a black tar heroin market are preparing heroin without heat. Additional research is needed to determine whether this is an endemic practice or PWID are engaging in new forms of drug preparation in response to changes in the environment.

Topics: Adult; California; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Prevalence; Substance Abuse, Intravenous

Harm reduction policies and attitudes in the United States have advanced substantially in recent years but still lag behind more advanced jurisdictions in Europe and elsewhere. The Obama administration, particularly in its last years, embraced some harm reduction policies that had been rejected by previous administrations but shied away from more cutting edge interventions like supervised consumption sites and heroin-assisted treatment. The Trump administration will undermine some of the progress made to date but significant state and local control over drug policies in the US, as well as growing Republican support for pragmatic drug policies, motivated in part by the opioid crisis, ensures continuing progress for harm reduction.

Topics: Analgesics, Opioid; Harm Reduction; Heroin; Heroin Dependence; Humans; Legislation, Medical; Marijuana Abuse; Needle-Exchange Programs; Politics; Public Policy; United States

Previous studies have shown that heroin abuse can alter the gonadal functions. Few studies examined the association between testosterone levels and heroin use in the existing literature. We aimed to determine the association between gonadal hormones and heroin usage characteristics over 12 weeks of abstinence in heroin users.. We collected data on patient demographics and heroin use patterns for 65 men aged 18 to 45 and for 29 age-matched healthy controls. Serum levels of total testosterone, estradiol, and prolactin were assessed at 5 time points.. Testosterone levels gradually increased and prolactin levels decreased in heroin users in this study. In heroin users, a significant positive correlation was observed between the way of using drug and the testosterone levels, the way of using drug and the estradiol levels, between the duration of heroin dependence and the testosterone levels, between the duration of heroin dependence and the estradiol levels on D0, and between relapse time and testosterone levels on D84.. Our data reveal testosterone might promote injection drug use and repeated relapse in male heroin users.

Topics: Adolescent; Adult; Estradiol; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Prolactin; Testosterone; Young Adult

Heroin consumption in major cities across China was estimated for the first time via wastewater-based epidemiology. Influent and effluent wastewater samples were collected from 49 wastewater treatment plants (WWTPs) in 24 major cities that cover all the geographic regions of the country. Concentrations of morphine, 6-acetylmorphine, and codeine were measured. Near complete removal of morphine by wastewater treatment processes was observed, whereas removal rates of codeine were slightly lower. Morphine loads were much higher than codeine loads at most WWTPs in China, a trend opposite to that in many European countries. In addition, morphine and codeine loads were strongly correlated at most WWTPs, indicating morphine and codeine in wastewater were predominantly from the same source, street heroin. At WWTPs in Guangzhou and Shenzhen, codeine loads were considerably higher than morphine loads, consistent with previous reports of codeine abuse (e.g., as cough syrup) among middle and high school students in Guangdong province. Heroin consumption was derived based on morphine loads and taking into account therapeutic use of morphine and codeine, as well as contribution of codeine and acetylcodeine in street heroin. Highest heroin consumption was observed in northwestern and southwestern China. The average heroin consumption of the sampled cities was 64.6±78.7mg/1000inh/d. The nation-wide average heroin consumption was much lower than that of methamphetamine, consistent with seizure data and numbers of registered heroin and methamphetamine users in China.

Topics: China; Cities; Codeine; Heroin; Heroin Dependence; Humans; Morphine; Substance Abuse Detection; Wastewater

Community-based overdose prevention programs first emerged in the 1990's and are now the leading public health intervention for overdose. Key elements of these programs are overdose education and naloxone distribution to people who use opioids and their social networks. We review the evolution of naloxone programming through the heroin overdose era of the 1990's, the prescription opioid era of the 2000's, and the current overdose crisis stemming from the synthetic opioid era of illicitly manufactured fentanyl and its analogues in the 2010's. We present current challenges arising in this new era of synthetic opioids, including variable potency of illicit drugs due to erratic adulteration of the drug supply with synthetic opioids, potentially changing efficacy of standard naloxone formulations for overdose rescue, potentially shorter overdose response time, and reports of fentanyl exposure among people who use drugs but are opioid naïve. Future directions for adapting naloxone programming to the dynamic opioid epidemic are proposed, including scale-up to new venues and social networks, new standards for post-overdose care, expansion of supervised drug consumption services, and integration of novel technologies to detect overdose and deliver naloxone.

Topics: Analgesics, Opioid; Community Health Services; Drug Overdose; Fentanyl; Heroin; Heroin Dependence; Humans; Illicit Drugs; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance-Related Disorders

US opioid overdose death rates have increased between 2000 and 2014. While, the increase in prescription opioid use has been linked to the increase in heroin use, there are reasons to view this relationship as a partial explanation for the recent increase in heroin-related harms. This study documents the differences in trends in prescription opioid overdose-related (POD) and heroin overdose-related (HOD) hospitalizations.. Data come from the National Inpatient Sample (NIS) for the years 2000 through 2014. POD and HOD hospitalizations were abstracted from ICD-9 codes. Rates of POD and HOD by census region and census division were constructed along with separate rates for age and race. Regression analysis analyzing trends across region were estimated along with graphs for documenting differences in POD and HOD rates.. POD hospitalization rates were highest in the South and lowest in the Northeast. HOD hospitalization rates were highest in the Northeast region and grew the fastest in the Midwest. There was statistically significant heterogeneity in HOD trends but not POD trends across the four regions between 2000 and 2014. Between 2012 and 2014 POD rates decreased in eight of the nine census divisions, with only New England showing an increase. HOD hospitalization rates increased in all nine census divisions between 2012 and 2014. Both POD and HOD rates show different demographic patterns across the nine census divisions.. Comparing POD and HOD hospitalization trends reveals significant disparities in geographic as well as demographic distributions. These epidemics are evolving and the simple opioid-to-heroin transition story is both supported and challenged by this paper. The opioid pill, heroin and fentanyl crises are intertwined yet increasingly have drivers and outcomes that support examining them as distinct. Addressing these complex and interrelated epidemics will require innovative public health research and interventions which need to consider local and regional contexts.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Fentanyl; Heroin; Heroin Dependence; Hospitalization; Humans; Male; Middle Aged; Opioid-Related Disorders; United States; Young Adult

More than a decade in the making, America's opioid crisis has morphed from being driven by prescription drugs to one fuelled by heroin and, increasingly, fentanyl. Drawing on historical lessons of the era of National Alcohol Prohibition highlights the unintended, but predictable impact of supply-side interventions on the dynamics of illicit drug markets. Under the Iron Law of Prohibition, efforts to interrupt and suppress the illicit drug supply produce economic and logistical pressures favouring ever-more compact substitutes. This iatrogenic progression towards increasingly potent illicit drugs can be curtailed only through evidence-based harm reduction and demand reduction policies that acknowledge the structural determinants of health.

Topics: Analgesics, Opioid; Fentanyl; Harm Reduction; Heroin; Heroin Dependence; Humans; Illicit Drugs; Opioid-Related Disorders; Public Policy; United States

The US is experiencing an unprecedented opioid overdose epidemic fostered in recent years by regional contamination of the heroin supply with the fentanyl family of synthetic opioids. Since 2011 opioid-related overdose deaths in the East Coast state of Massachusetts have more than tripled, with 75% of the 1374 deaths with an available toxicology positive for fentanyl. Fentanyl is 30-50X more potent than heroin and its presence makes heroin use more unpredictable. A rapid ethnographic assessment was undertaken to understand the perceptions and experiences of people who inject drugs sold as 'heroin' and to observe the drugs and their use.. A team of ethnographers conducted research in northeast Massachusetts and Nashua, New Hampshire in June 2016, performing (n=38) qualitative interviews with persons who use heroin.. (1) The composition and appearance of heroin changed in the last four years; (2) heroin is cheaper and more widely available than before; and (3) heroin 'types' have proliferated with several products being sold as 'heroin'. These consisted of two types of heroin (alone), fentanyl (alone), and heroin-fentanyl combinations. In the absence of available toxicological information on retail-level heroin, our research noted a hierarchy of fentanyl discernment methods, with embodied effects considered most reliable in determining fentanyl's presence, followed by taste, solution appearance and powder color. This paper presents a new 'heroin' typology based on users' reports.. Massachusetts' heroin has new appearances and is widely adulterated by fentanyl. Persons who use heroin are trying to discern the substances sold as heroin and their preferences for each form vary. The heroin typology presented is inexact but can be validated by correlating users' discernment with drug toxicological testing. If validated, this typology would be a valuable harm reduction tool. Further research on adaptations to heroin adulteration could reduce risks of using heroin and synthetic opioid combinations.

Topics: Adult; Drug Contamination; Drug Overdose; Drug Users; Female; Fentanyl; Harm Reduction; Heroin; Heroin Dependence; Humans; Interviews as Topic; Male; Massachusetts; Middle Aged; New Hampshire; Opioid-Related Disorders; Substance Abuse Detection; Uncertainty; United States; Young Adult

The study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance.. The study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky.. Fentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25-34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; <40% of the heroin overdose ED discharge records listed procedure codes for drug screening.. The lack of routine ED drug testing likely resulted in underreporting of non-fatal overdoses involving fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Drug Contamination; Drug Overdose; Female; Fentanyl; Heroin; Heroin Dependence; Humans; Kentucky; Male; Middle Aged; Opioid-Related Disorders; Public Health; Substance-Related Disorders; Young Adult

Chronic heroin use can cause deficits in response inhibition, leading to a loss of control over drug use, particularly in the context of drug-related cues. Unfortunately, heightened incentive salience and motivational bias in response to drug-related cues may exist following abstinence from heroin use.. The present study aimed to examine the effect of drug-related cues on response inhibition in long-term heroin abstainers.. Sixteen long-term (8-24 months) male heroin abstainers and 16 male healthy controls completed a modified two-choice oddball paradigm, in which a neutral "chair" picture served as frequent standard stimuli; the neutral and drug-related pictures served as infrequent deviant stimuli of different conditions respectively. Event-related potentials were compared across groups and conditions.. Our results showed that heroin abstainers exhibited smaller N2d amplitude (deviant minus standard) in the drug cue condition compared to the neutral condition, due to smaller drug-cue deviant-N2 amplitude compared to neutral deviant-N2. Moreover, heroin abstainers had smaller N2d amplitude compared with the healthy controls in the drug cue condition, due to the heroin abstainers having reduced deviant-N2 amplitude compared to standard-N2 in the drug cue condition, which reversed in the healthy controls.. Our findings suggested that heroin addicts still show response inhibition deficits specifically for drug-related cues after longer-term abstinence. The inhibition-related N2 modulation for drug-related could be used as a novel electrophysiological index with clinical implications for assessing the risk of relapse and treatment outcome for heroin users.

Topics: Adult; Choice Behavior; Craving; Cues; Evoked Potentials; Heroin; Heroin Dependence; Humans; Inhibition, Psychological; Male; Middle Aged; Motivation; Recurrence; Substance Withdrawal Syndrome; Young Adult

To date there have been no studies investigating the characteristics of pain in Chinese heroin-dependent patients (HDPs) receiving methadone maintenance treatment (MMT). This study examined the frequency and socio-demographic and clinical correlates of pain in HDPs under MMT. A consecutive sample of 603 HDPs was recruited from three MMT clinics in Wuhan, China. These patients completed a standardized questionnaire concerning socio-demographic and clinical data. Pain intensity was assessed with the 5-point Verbal Rating Scale ("Overall, how intense is your pain now?") with responses of: 1 = none, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe. A pain score of three or higher was used to denote clinical significant pain (CSP). The prevalence of CSP in HDPs receiving MMT was 53.6%. Factors significantly associated CSP in multiple logistics regression analysis were old age, marital status of "non-married", unemployment, having religious beliefs, a history of injecting heroin, a high dose of methadone, and more depressive symptoms. Over a half of Chinese HDPs receiving MMT have CSP. Services for HDPs in MMT settings should include periodic screening for pain, psychosocial supports, and professional treatment for pain.

Topics: Adult; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Pain; Prevalence; Public Health Surveillance; Socioeconomic Factors; Young Adult

Topics: Aged; Cardiopulmonary Resuscitation; Drug Overdose; Heroin; Heroin Dependence; Humans; Male; Naloxone; Narcotic Antagonists; Narcotics; Pneumoperitoneum; Radiography, Thoracic; Respiratory Insufficiency; Stomach; Tomography, X-Ray Computed

This study assesses whether opioid-related gene variants contribute to reduced vulnerability to relapse to heroin in persons who are not treated with μ-opioid receptor agonist.. Genotypes of 71 SNPs, in nine genes, were analyzed for association with long-term abstinence in former heroin-dependents of European/Middle Eastern ancestry, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 922).. The functional OPRM1 nonsynonymous SNP rs1799971 (118A>G) showed significant association with long-term abstinence (P. Since the stress axis is regulated in part by β-endorphin, this functional OPRM1 SNP may blunt the endogenous stress response and contribute to reduced vulnerability for relapse.

Topics: Analgesics, Opioid; Female; Genotype; Heroin; Heroin Dependence; Humans; Male; Methadone; Polymorphism, Single Nucleotide; Receptors, Opioid, mu; White People

Superoxide dismutase-1 (SOD1, OMIM: 147450) is one of the major antioxidant enzymes, which plays a vital role in clearance of reactive oxygen species. A genetic polymorphism of 50 bp insertion/deletion (Ins/Del) in the promoter region of the SOD1 was reported. The aims of the present study are to evaluate the influence of this polymorphism on the SOD1 mRNA levels in human peripheral blood cells and its association with risk of heroin dependency.. The present study consisted of 47 healthy students of Shiraz University (south-west Iran) for investigating the association between the Ins/Del polymorphism on expression level of SOD1, also a total of 442 heroin dependent and 799 healthy controls were included in a case-control study investigating the association between the study polymorphism and risk of dependency to heroin. The quantitative SOD1 mRNA expression levels were investigated using quantitative real-time PCR.. Statistical analysis revealed a significant difference between the study genotypes (t = 5.17; df = 45; P < 0.001). The Del allele of the study polymorphism decreased approximately 33% of the SOD1 mRNA levels of the gene in the heterozygote individuals. Statistical analysis indicating that in both genders, neither the Ins/Del nor the Del/Del genotypes was associated with the risk of heroin addiction.. The present study indicating that although the Ins/Del polymorphism of SOD1 is associated with the SOD1 expression levels, this polymorphism is not associated with the risk of dependency to heroin.

Topics: Adult; Female; Gene Expression; Heroin; Heroin Dependence; Humans; INDEL Mutation; Iran; Male; Polymorphism, Genetic; Promoter Regions, Genetic; Superoxide Dismutase-1; Young Adult

Topics: Adult; Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Heroin Dependence; Humans; Hypoxia; Lung; Male; Naloxone; Narcotic Antagonists; Pulmonary Edema; Radiography, Thoracic; Substance Abuse, Intravenous

To compare the effects of heroin and methamphetamine (METH) addiction on dopamine transporters (DATs) in the same dose and duration, we assessed DAT levels in the striatum by

Topics: Adult; Amphetamine-Related Disorders; Caudate Nucleus; Chronic Disease; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Heroin; Heroin Dependence; Humans; Male; Methamphetamine; Middle Aged; Putamen; Tomography, Emission-Computed, Single-Photon; Young Adult

Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals.

Topics: Animals; Antidepressive Agents, Second-Generation; Behavior, Animal; Disease Models, Animal; Fluoxetine; Grooming; Heroin; Heroin Dependence; Male; Mice; Mice, Inbred C57BL; Naltrexone; Narcotic Antagonists; Receptors, Opioid, kappa; Social Behavior; Time; Treatment Outcome

Addiction is characterized by drug craving, compulsive drug taking and relapse, which is attributed to aberrant neuroadaptation in brain regions implicated in drug addiction, induced by changes in gene and protein expression in these regions after chronic drug exposure. Accumulating evidence suggests that the dorsal hippocampus (DH) plays an important role in mediating drug-seeking and drug-taking behavior and relapse. However, the molecular mechanisms underlying these effects of the DH are unclear. In the present study, we employed a label-free quantitative proteomic approach to analyze the proteins altered in the DH of heroin self-administering rats. A total of 4015 proteins were quantified with high confidence, and 361 proteins showed significant differences compared with the saline control group. Among them, cyclin-dependent kinase 5 (CDK5) and ras homolog family member B (RhoB) were up-regulated in rats with a history of extended access to heroin. Functionally, inhibition of CDK5 in the DH enhanced heroin self-administration, indicating that CDK5 signaling in the DH acts as a homeostatic compensatory mechanism to limit heroin-taking behavior, whereas blockade of the Rho-Rho kinase (ROCK) pathway attenuated context-induced heroin relapse, indicating that RhoB signaling in the DH is required for the retrieval (recall) of addiction memory. Our findings suggest that manipulation of CDK5 signaling in the DH may be essential in determining vulnerability to opiate taking, whereas manipulation of RhoB signaling in the DH may be essential in determining vulnerability to relapse. Overall, the present study suggests that the DH can exert dissociative effects on heroin addiction through CDK5 and RhoB signaling.

Topics: Animals; Behavior, Animal; Cyclin-Dependent Kinase 5; Disease Models, Animal; Drug-Seeking Behavior; Heroin; Heroin Dependence; Hippocampus; Male; Narcotics; Proteomics; Rats; Rats, Sprague-Dawley; Recurrence; rhoB GTP-Binding Protein; Self Administration; Signal Transduction

Gender differences in illicit drug use are becoming increasingly recognized. However, there are few studies concerning differences between male and female heroin users in China.. The study aimed to explore gender differences in terms of socio-demographic characteristics, drug-related behaviors, and treatment history among a heroin-using population in China.. A cross-sectional study was conducted in four cities in December 2013. A total of 788 participants were recruited from several types of sites in each city: compulsory detoxification centers, methadone maintenance treatment clinics, and detention facilities. The data were collected via a self-administered questionnaire. Analysis of variance, chi-square test, and multivariate logistic regression analyses were conducted to examine gender differences in socio-demographic characteristics, drug-related behaviors, and treatment history.. Female heroin users were more likely to be unemployed, have more education, and use heroin with their spouse/companion (p <.05). Male heroin users were more likely to be in detention facilities and MMT clinics, and relapse when they felt hopeless (p <.05). Conclusions/Importance: Although there were some similarities between male and female heroin users, significant gender differences do exist in some aspects of socio-demographic characteristics and heroin use. The data provide evidence that interventions aimed at preventing the initiation of heroin use and reducing relapse should take gender into account.

Topics: Adult; China; Cross-Sectional Studies; Drug Users; Educational Status; Employment; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Sex Characteristics; Surveys and Questionnaires

A 29-year-old man was admitted for acute cognitive impairment. Three weeks earlier, he had been admitted for coma due to sniffed heroin abuse responsive to naloxone infusion. At admission, the patient presented with apraxia, severe memory impairment and anosognosia. Brain MRI revealed symmetric hyperintensities of supratentorial white matter, sparing brainstem and cerebellum, on FLAIR and B1000 sequences. Four months later, repeated neuropsychological assessment revealed dramatic improvement of global cognitive functions. Toxic leucoencephalopathy excluding the cerebellum and brainstem is a rare complication of heroin abuse, and seems to concern especially patients that use heroin by sniff or injection. In these patients, cognitive troubles are predominant, prognosis seems better and infratentorial brain structures can be spared. In conclusion, our observation emphasizes that heroin-induced encephalopathy can have a favourable outcome and that imaging and clinical patterns can indicate the mode of drug administration.

Topics: Administration, Inhalation; Adult; Brain; Cognition Disorders; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Narcotics; Neuropsychological Tests

Herpes simplex virus type 2 (HSV-2) infection increases both susceptibility to and transmissibility of human immunodeficiency virus (HIV), and HSV-2 and HIV are often strongly associated in HIV epidemics. We assessed trends in HSV-2 prevalence among non-injecting drug users (NIDUs) when HIV prevalence declined from 16% to 8% among NIDUs in New York City.. Subjects were current non-injecting users of heroin and/or cocaine and who had never injected illicit drugs. Three thousand one hundred fifty-seven NIDU subjects were recruited between 2005 and 2014 among persons entering Mount Sinai Beth Israel substance use treatment programs. Structured interviews, HIV, and HSV-2 testing were administered. Change over time was assessed by comparing 2005 to 2010 with 2011 to 2014 periods. Herpes simplex virus type 2 incidence was estimated among persons who participated in multiple years.. Herpes simplex virus type 2 prevalence was strongly associated with HIV prevalence (odds ratio, 3.9; 95% confidence interval, 2.9-5.1) from 2005 to 2014. Herpes simplex virus type 2 prevalence declined from 60% to 56% (P = 0.01). The percentage of NIDUs with neither HSV-2 nor HIV infection increased from 37% to 43%, (P < 0.001); the percentage with HSV-2/HIV coinfection declined from 13% to 6% (P < 0.001). Estimated HSV-2 incidence was 1 to 2/100 person-years at risk.. There were parallel declines in HIV and HSV-2 among NIDUs in New York City from 2005 to 2014. The increase in the percentage of NIDUs with neither HSV-2 nor HIV infection, the decrease in the percentage with HSV-2/HIV coinfection, and the low to moderate HSV-2 incidence suggest some population-level protection against resurgence of HIV. Prevention efforts should be strengthened to end the combined HIV/HSV-2 epidemic among NIDUs in New York City.

Topics: Adolescent; Adult; Cocaine; Cocaine-Related Disorders; Coinfection; Drug Users; Female; Heroin; Heroin Dependence; Herpes Simplex; Herpesvirus 2, Human; Heterosexuality; HIV Infections; Humans; Male; Middle Aged; New York City; Prevalence; Substance Abuse, Intravenous; Young Adult

Opioid addiction, including addiction to heroin, has markedly increased in the past decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction, particularly in individuals who are resistant to traditional therapies. Here we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction. STN HFS prevented the re-escalation of heroin intake after abstinence in rats with extended access to heroin, an animal model of compulsive heroin taking. STN HFS inhibited key brain regions, including the substantia nigra, entopeduncular nucleus, and nucleus accumbens shell measured using brain mapping analyses of immediate-early gene expression and produced a robust silencing of STN neurons as measured using whole-cell recording ex vivo. These results warrant further investigation to examine the therapeutic effects that STN HFS may have on relapse in humans with heroin addiction.

Topics: Analgesics, Opioid; Animals; Compulsive Behavior; Deep Brain Stimulation; Disease Models, Animal; Drug-Seeking Behavior; Heroin; Heroin Dependence; Male; Membrane Potentials; Proto-Oncogene Proteins c-fos; Rats, Wistar; Self Administration; Subthalamic Nucleus; Tissue Culture Techniques

Topics: Analgesics, Opioid; Animals; Dentate Gyrus; Disease Models, Animal; Drug-Seeking Behavior; Entorhinal Cortex; Glutamic Acid; Heroin; Heroin Dependence; Male; MAP Kinase Signaling System; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Saccharin; Synaptic Transmission

In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. We previously demonstrated that the projections from ventral medial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) shell play a role in this reinstatement. The ventral subiculum (vSub) sends glutamate projections to NAc shell and vmPFC. Here, we determined whether these projections contribute to context-induced reinstatement.. We trained rats to self-administer heroin (0.05-0.1 mg/kg/infusion) for 3 h per day for 12 days; drug infusions were paired with a discrete tone-light cue. Lever pressing in the presence of the discrete cue was subsequently extinguished in a different context. We then tested the rats for reinstatement in the heroin- and extinction-associated contexts under extinction conditions. We combined Fos with the retrograde tracer Fluoro-Gold (FG) to determine projection-specific activation during the context-induced reinstatement tests. We also used anatomical disconnection procedures to determine whether the vSub → NAc shell and vSub → vmPFC projections are functionally involved in this reinstatement.. Exposure to the heroin but not the extinction context reinstated lever pressing. Context-induced reinstatement of heroin seeking was associated with increased Fos expression in vSub neurons, including those projecting to NAc shell and vmPFC. Anatomical disconnection of the vSub → NAc shell projection, but not the vSub → vmPFC projection, decreased this reinstatement.. Our data indicate that the vSub → NAc shell glutamatergic projection, but not the vSub → vmPFC projection, contributes to context-induced reinstatement of heroin seeking.

Topics: Animals; Cues; Extinction, Psychological; Glutamic Acid; Heroin; Heroin Dependence; Hippocampus; Male; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration

Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

Topics: Analgesics, Non-Narcotic; Analysis of Variance; Animals; Conditioning, Operant; Disease Models, Animal; Dronabinol; Female; Heroin; Heroin Dependence; Macaca mulatta; Male; Narcotics; Reinforcement, Psychology; Self Administration

While relatively rare events, abrupt disruptions in heroin availability have a significant impact on morbidity and mortality risk among those who are heroin dependent. A heroin shortage occurred in Coast Province, Kenya from December 2010 to March 2011. This qualitative analysis describes the shortage events and consequences from the perspective of heroin users, along with implications for health and other public sectors.. As part of a rapid assessment, 66 key informant interviews and 15 focus groups among heroin users in Coast Province, Kenya were conducted. A qualitative thematic analysis was undertaken in Atlas.ti. to identify salient themes related to the shortage.. Overall, participant accounts were rooted in a theme of desperation and uncertainty, with emphasis on six sub-themes: (1) withdrawal and strategies for alleviating withdrawal, including use of medical intervention and other detoxification attempts; (2) challenges of dealing with unpredictable drug availability, cost, and purity; (3) changes in drug use patterns, and actions taken to procure heroin and other drugs; (4) modifications in drug user relationship dynamics and networks, including introduction of risky group-level injection practices; (5) family and community response; and (6) new challenges with the heroin market resurgence.. The heroin shortage led to a series of consequences for drug users, including increased risk of morbidity, mortality and disenfranchisement at social and structural levels. Availability of evidence-based services for drug users and emergency preparedness plans could have mitigated this impact.

Topics: Drug Users; Female; Focus Groups; Heroin; Heroin Dependence; Humans; Interviews as Topic; Kenya; Male; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

The ability to predict individual vulnerability to substance abuse would allow for a better understanding of the progression of the disease and development of better methods for prevention and/or early intervention. Here we use drug-induced devaluation of a saccharin cue in an effort to predict later addiction-like behavior in a model akin to that used by Deroche-Gamonet et al. (2004) and seek to link such vulnerability to changes in expression of various mu opioid receptor and D2 receptor-interacting proteins in brain. The results show that the greatest heroin-induced suppression of intake of a saccharin cue is associated with the greatest vulnerability to later addiction-like behavior and to differences in the expression of WLS, β-catenin, and NCS-1 in brain compared to rats that exhibited the least suppression of intake of the heroin-paired cue and/or saline controls. Finally, because the self-administration model employed produced no significant differences in drug intake between groups, overall, the resultant changes in protein expression can be more closely linked to individual differences in motivation for drug.

Topics: Animals; Behavior, Animal; beta Catenin; Cues; Heroin; Heroin Dependence; Male; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Saccharin; Self Administration; Taste; Taste Perception

The initiation of injecting drug use and the commencement of a pattern of regular injecting are key milestones in injecting careers. The progression from initiation to regular injecting is a poorly understood period in these careers.. Cross-sectional baseline data from a sample of people who inject drugs regularly (N=691), recorded the age at which participants initiated injecting drug use and the age they became regular (at least once per month) injectors. Survival analysis compared the rapidity of progression to regular injecting across sub-groups within the sample using bivariate log-rank testing and multivariable Cox regression.. Half of all participants progressed to regular injecting within 1 year of initiation and by the fourth year post-initiation, 91% had progressed. In bivariate analysis, there were significant differences in equality of hazards by sex (X(2)=7.75, p<0.01), from whom participants learnt to inject (X(2)=22.32, p<0.01) and the drug of injection initiation (X(2)=18.36; p<0.01). In the multivariable Cox model, only initiating injecting with heroin (HR=1.28; 95% CI: 1.09-1.50) compared with other drugs (predominantly methamphetamine) showed a significantly greater hazard, suggesting a faster progression to regular injecting.. This study showed that among our sample of eventual regular injectors, progression from initiation to regular injecting was rapid. By gaining a greater understanding of the dynamics of this progression, the ability to appropriately target interventions and future research is subsequently informed.

Topics: Adolescent; Adult; Child; Cohort Studies; Cross-Sectional Studies; Disease Progression; Female; Heroin; Heroin Dependence; Humans; Male; Methamphetamine; Retrospective Studies; Substance Abuse, Intravenous; Survival Analysis; Young Adult

One of the most damaging aspects of drug addiction is the degree to which natural rewards (family, friends, employment) are devalued in favor of seeking, obtaining and taking drugs. We have utilized an animal model of reward devaluation and heroin self-administration to explore the role of the coricotropin releasing factor (CRF) pathway. Given access to a saccharin cue followed by the opportunity to self-administer heroin, animals will parse into distinct phenotypes that suppress their saccharin intake (in favor of escalating heroin self-administration) or vice versa. We find that large saccharin suppressors (large heroin takers) demonstrate increased mRNA expression for elements of the CRF signaling pathway (CRF, CRF receptors and CRF binding protein) within the hippocampus, medial prefrontal cortex and the ventral tegmental area. Moreover, there were no gene expression changes of these components in the nucleus accumbens. Use of bisulfite conversion sequencing suggests that changes in CRF binding protein and CRF receptor gene expression may be mediated by differential promoter methylation.

Topics: Animals; Corticotropin-Releasing Hormone; Cues; Heroin; Heroin Dependence; Hippocampus; Male; Nucleus Accumbens; Prefrontal Cortex; Rats; Reward; Saccharin; Self Administration; Ventral Tegmental Area

Heroin addiction is a disease of chronic relapse that harms the individual through devaluation of personal responsibilities in favor of finding and using drugs. Only some recreational heroin users devolve into addiction but the basis of these individual differences is not known. We have shown in rats that avoidance of a heroin-paired taste cue reliably identifies individual animals with greater addiction-like behavior for heroin. Here rats received 5min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 6h. Large Suppressors of the heroin-paired taste cue displayed increased drug escalation, motivation for drug, and drug loading behavior compared with Small Suppressors. Little is known about the molecular mechanisms of these individual differences in addiction-like behavior. We examined the individual differences in mRNA expression in the nucleus accumbens (NAc) of rats that were behaviorally stratified by addiction-like behavior using next-generation sequencing. We hypothesized that based on the avoidance of the drug-paired cue there will be a unique mRNA profile in the NAc. Analysis of strand-specific whole genome RNA-Seq data revealed a number of genes differentially regulated in NAc based on the suppression of the natural saccharine reward. Large Suppressors exhibited a unique mRNA prolife compared to Saline controls and Small Suppressors. Genes related to immunity, neuronal activity, and behavior were differentially expressed among the 3 groups. In total, individual differences in avoidance of a heroin-paired taste cue are associated with addiction-like behavior along with differential NAc gene expression.

Topics: Animals; Brain; Conditioning, Operant; Cues; Heroin; Heroin Dependence; Individuality; Male; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Reward; Saccharin; Self Administration; Taste; Taste Perception; Transcriptome

Topics: Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Substance Abuse, Intravenous; Vascular Diseases

Craving for substance use has been added as one of the diagnostic criteria of substance use disorders in DSM-5. However, further research is necessary to examine and expand the clinical potential of craving in the assessment and treatment for heroin users. This study aimed to examine the psychometrics of the Desire for Drug Questionnaire-Chinese Mandarin version (DDQ-CM) and its clinical utility of assessing craving for heroin measured among heroin users with methadone maintenance treatment (MMT).. Self-reported craving for heroin use was measured on the DDQ-CM and visual analog scale among 314 intravenous heroin users receiving MMT. Self-reported heroin dependence, attitude toward heroin use, readiness to change heroin use, and depression were collected.. The results found that although the original three-factor model was acceptable for applying the DDQ-CM for heroin users with MMT, only the concurrent validity of the subscales of Desire and Intention and Negative Reinforcement was supported but not that of Control. Meanwhile, the levels of craving on the subscales of Desire and Intention and of Negative Reinforcement on the DDQ-CM were positively associated with the levels of heroin dependence, positive and negative attitudes toward heroin use, and depression, but negatively associated with readiness to change heroin use.. This study supported the application of the subscales of Desire and Intention and Negative Reinforcement on the DDQ-CM to measure heroin craving in Taiwanese-Chinese heroin users and supported the clinical implication of craving in heroin users with MMT.

Topics: Adolescent; Adult; Craving; Depression; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Psychometrics; Surveys and Questionnaires; Taiwan

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of heroin dependence. BDNF expression is dramatically changed during drug withdrawal, and is associated with drug withdrawal syndrome. This study aimed to explore (1) alterations of BDNF serum levels in heroin-dependent patients after long term abstinence; and (2) the association between BDNF serum levels and protracted withdrawal syndrome.. Fifty-three male heroin-dependent patients and fifty-two gender-matched healthy controls were enrolled in this study. We measured BDNF serum levels at baseline and 26 weeks after heroin abstinence. Moreover, protracted withdrawal symptoms, depression and anxiety symptoms were measured by Protracted Withdrawal Symptoms of Heroin-dependent patients (PWSHA), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS), respectively.. We found that baseline BDNF serum levels were significantly lower in heroin-dependent patients compared to controls (p<0.01). There was also a significantly difference in BDNF serum levels among heroin-dependent patients at baseline and 26-week follow-up (p<0.01). The BDNF serum levels were not associated with age, BMI, years of education, age of initial use, or duration of use. Of the clinical symptoms measured, the change in BDNF serum levels from baseline to 26-week follow-up was negatively associated with the change in PWSHA scores (r = -0.44, p<0.01, see Table 2 and Figure 2 for details).. The results show that the BDNF serum levels in heroin-dependent patients are lower than those of healthy controls at baseline and increased after 26 weeks of abstinence, although the BDNF serum levels are still lower than those of the healthy controls. A negative correlation between the change in BDNF serum levels and protracted withdrawal symptoms was found but needs to be confirmed in further study. The results revealed that BDNF serum level is worth paying attention to in order to further investigate the possibility of it being a biomarker of treatment outcome for opiate dependence.

Topics: Adult; Anxiety; Biomarkers; Brain-Derived Neurotrophic Factor; Case-Control Studies; Conduct Disorder; Depression; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Substance Withdrawal Syndrome; Time Factors

Increases in illicit pharmaceutical opioid (PO) use have been associated with risk for transition to heroin use. We identify predictors of transition to heroin use among young, illicit PO users with no history of opioid dependence or heroin use at baseline.. Respondent-driven sampling recruited 383 participants; 362 returned for at least one biannual structured interview over 36 months. Cox regression was used to test for associations between lagged predictors and hazard of transition to heroin use. Potential predictors were based on those suggested in the literature. We also computed population attributable risk (PAR) and the rate of heroin transition.. Over 36 months, 27 (7.5%) participants initiated heroin use; all were white, and the rate of heroin initiation was 2.8% per year (95% CI=1.9%-4.1%). Mean length of PO at first reported heroin use was 6.2 years (SD=1.9). Lifetime PO dependence (AHR=2.39, 95% CI=1.07-5.48; PAR=32%, 95% CI=-2% to 64%), early age of PO initiation (AHR=3.08, 95%; CI=1.26-7.47; PAR=30%, 95% CI=2%-59%), using illicit POs to get high but not to self-medicate a health problem (AHR=4.83, 95% CI=2.11-11.0; PAR=38%, 95% CI=12%-65%), and ever using PO non-orally most often (AHR=6.57, 95% CI=2.81-17.2; PAR=63%, 95% CI=31%-86%) were significant predictors.. This is one of the first prospective studies to test observations from previous cross-sectional and retrospective research on the relationship between illicit PO use and heroin initiation among young, initially non-opioid dependent PO users. The results provide insights into targets for the design of urgently needed prevention interventions.

Topics: Adult; Age Factors; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Male; Ohio; Opioid-Related Disorders; Prescription Drug Misuse; Proportional Hazards Models; Prospective Studies; Retrospective Studies; Surveys and Questionnaires; Time Factors; White People; Young Adult

Contrary to popular belief, policies on drug use are not always based on scientific evidence or composed in a rational manner. Rather, decisions concerning drug policies reflect the negotiation of actors' ambitions, values, and facts as they organize in different ways around the perceived problems associated with illicit drug use. Drug policy is thus best represented as a complex adaptive system (CAS) that is dynamic, self-organizing, and coevolving. In this analysis, we use a CAS framework to examine how harm reduction emerged around heroin trafficking and use in Tanzania over the past thirty years (1985-present). This account is an organizational ethnography based on of the observant participation of the authors as actors within this system. We review the dynamic history and self-organizing nature of harm reduction, noting how interactions among system actors and components have coevolved with patterns of heroin us, policing, and treatment activities over time. Using a CAS framework, we describe harm reduction as a complex process where ambitions, values, facts, and technologies interact in the Tanzanian sociopolitical environment. We review the dynamic history and self-organizing nature of heroin policies, noting how the interactions within and between competing prohibitionist and harm reduction policies have changed with patterns of heroin use, policing, and treatment activities over time. Actors learn from their experiences to organize with other actors, align their values and facts, and implement new policies. Using a CAS approach provides researchers and policy actors a better understanding of patterns and intricacies in drug policy. This knowledge of how the system works can help improve the policy process through adaptive action to introduce new actors, different ideas, and avenues for communication into the system.

Topics: Drug Trafficking; Harm Reduction; Health Policy; Heroin; Heroin Dependence; Humans; Policy Making; Tanzania

Over the last 20 years, supervised injectable and inhalable heroin prescribing has been developed, tested and in some cases introduced as a second line treatment for limited groups of entrenched heroin users in a number of European countries and Canada. Based on documentary analyses and eleven key informant interviews, this paper investigates the growth of 'expertise' and the sharing of knowledge between scientific stakeholders from different countries involved in researching and developing this area of treatment. Drawing on Stone's concept of the 'knowledge network' (Stone, 2013) and Gieryn's theory of 'boundary-work' (Gieryn, 1983), the analysis demonstrates the collective power of this group of scientists in producing a particular form of knowledge and expertise which has accrued and been exchanged over time. It also illustrates the ways in which this type of science has gained credibility and authority and become legitimised, reinforced and reproduced by those who employ it in both scientific and political debates. Boundaries were constructed by the knowledge network between different types of professions/disciplines, different forms of science and between the production of science and its consumption by non-scientists. The uniformity of the knowledge network in terms of their professional and disciplinary backgrounds, methodological expertise and ideological perspectives has meant that alternative forms of knowledge and perspectives have been neglected. This limits the nature and scope of the scientific evidence on which to base policy and practice decisions impacting on the work of policy makers and practitioners as well as the experiences of those in treatment who are most affected by this research and policy development.

Topics: Administration, Inhalation; Analgesics, Opioid; Behavior, Addictive; Cooperative Behavior; Drug Users; Evidence-Based Medicine; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Interdisciplinary Communication; International Cooperation; Knowledge Bases; Public Opinion; Qualitative Research; Stakeholder Participation; Treatment Outcome

Topics: Administration, Inhalation; Adult; Diagnosis, Differential; Dyspnea; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Opiate Substitution Treatment; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Spouses; Tomography, X-Ray Computed

Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re-selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible biases in how respondents describe their drug dealing activities.

Topics: Cocaine; Cocaine-Related Disorders; Commerce; Drug and Narcotic Control; Drug Costs; Drug Trafficking; Efficiency, Organizational; Heroin; Heroin Dependence; Humans; Italy; Models, Economic; Models, Organizational; Policy Making; Slovenia

Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.

Topics: Adult; Androstanes; Cytochrome P-450 CYP2B6; Extracellular Matrix Proteins; Female; Genome-Wide Association Study; Haplotypes; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Pharmacogenetics; Polymorphism, Single Nucleotide; Stereoisomerism

Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic-pituitary-adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.

Topics: Adult; Analgesics, Opioid; Hair; Heroin; Heroin Dependence; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Pituitary-Adrenal System; Young Adult

Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse.

Topics: Adult; Cues; Female; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Inhibition, Psychological; Male; Middle Aged; Narcotics; Neuropsychological Tests

Identification of external contamination is a challenge in hair analysis. This study investigates metabolite ratios of hydromorphone to morphine and hydrocodone to codeine as indicators to distinguish contamination from heroin use provided that hydromorphone/hydrocodone intake is excluded.. Hair samples after external contamination with street heroin proved to be negative for hydromorphone/hydrocodone. Hair samples from individuals with suspected street heroin use/contamination or opiate medication were analyzed for 6-monoacetylmorphine, morphine, acetylcodeine, codeine, hydromorphone and hydrocodone, and metabolite ratios of hydromorphone to morphine and hydrocodone to codeine were assessed. Hair samples from individuals with medicinal heroin/morphine/codeine use displayed significantly higher metabolite ratios than those with suspected street heroin use/contamination.. Hydromorphone/hydrocodone are solely formed during body passage. Thus, metabolite ratios can be used to distinguish morphine/heroin use from external contamination.

Topics: Analgesics, Opioid; Chromatography, Liquid; Female; Hair; Heroin; Heroin Dependence; Humans; Hydrocodone; Hydromorphone; Male; Morphine; Morphine Derivatives; Opiate Alkaloids; Substance Abuse Detection; Tandem Mass Spectrometry

Heroin has a half-life of 2-6 min and is metabolized too quickly to be detected in autopsy samples. The presence of 6-acetylmophine (6-AM) in urine, blood, or other samples is convincing evidence of heroin use by a decedent, but 6-AM itself has a half-life of 6-25 min before it is hydrolyzed to morphine, so 6-AM may not be present in sufficient concentration to detect in postmortem samples. Codeine is often present in heroin preparations as an impurity and is not a metabolite of heroin. Studies report that a ratio of morphine to codeine greater than one indicates heroin use. We hypothesize that the ratio of morphine to codeine in our decedents abusing drugs intravenously will be no different in individuals with 6-AM present than in individuals where no 6-AM is detected, and we report our study of this hypothesis.. All accidental deaths investigated by the Jefferson County Coroner/Medical Examiner Office from 2010 to 2013 with morphine detected in blood samples collected at autopsy were reviewed. Five deaths where trauma caused or contributed to death were excluded from the review. The presence or absence of 6-AM and the concentrations of morphine and codeine were recorded for each case. The ratio of morphine to codeine was calculated for all decedents. Any individual in whom no morphine or codeine was detected in a postmortem sample was excluded from further study. Absence or presence of drug paraphernalia or evidence of intravascular (IV) drug use was documented in each case to identify IV drug users. The proportion of the IV drug users with and without 6-AM present in a postmortem sample was compared to the M/C ratio for the individuals.. Of the 230 deaths included in the analysis, 103 IV drug users with quantifiable morphine and codeine in a postmortem sample were identified allowing for calculation of an M/C ratio. In these IV drug users, the M/C ratio was greater than 1 in 98 % of decedents. When controlling for the absence or presence of 6-AM there was no statistically significant difference in the proportion of IV drug users when compared to non IV drug users with an M/C ratio of greater than 1 (p = 1.000).. The M/C ratio in IV drug users, if greater than 1, is seen in deaths due to heroin toxicity where 6-AM is detected in a postmortem sample. This study provides evidence that a M/C ratio greater than one in an IV drug user is evidence of a death due to heroin toxicity even if 6-AM is not detected in the blood. Using the M/C ratio, in addition to scene and autopsy findings, provides sufficient evidence to show heroin is the source of the morphine and codeine. Listing heroin as a cause or contributing factor in deaths with evidence of IV drug abuse and where the M/C ratio exceeds 1 will improve identification of heroin fatalities, which will allow better allocation of resources for public health initiatives.

Topics: Codeine; Forensic Toxicology; Half-Life; Heroin; Heroin Dependence; Humans; Morphine; Morphine Derivatives; Narcotics; Postmortem Changes; Retrospective Studies; Substance Abuse Detection; Substance Abuse, Intravenous

Heroin-related cues can trigger craving and relapse in addicts or heroin seeking in rats. In the present study we investigated whether environmental enrichment (EE) implemented after heroin exposure can reduce cue-induced reinstatement of heroin seeking and expression of heroin conditioned place preference.. In Experiment 1, male Long Evans rats that already acquired a heroin self-administration habit, were housed in enriched or non-enriched environments, underwent extinction training and later were tested for cue-induced reinstatement of heroin seeking. In Experiment 2, rats were conditioned with heroin in one compartment of a CPP apparatus and saline in the other, exposed to 30days of enrichment or no enrichment and were later tested for heroin CPP.. The results showed that exposure to EE significantly reduced responding during the reinstatement test (Experiment 1) and prevented the expression of heroin CPP (Experiment 2).. Our findings suggest that EE can be an effective behavioral approach to diminish the effects of conditioned cues on heroin seeking.

Topics: Animals; Conditioning, Psychological; Cues; Environment; Extinction, Psychological; Heroin; Heroin Dependence; Male; Rats; Rats, Long-Evans; Self Administration

Little is known about trends in national rates of injection-related skin and soft tissue infections (SSTI) and their relationship to the structural risk environment for heroin users. Use of Mexican-sourced "Black Tar" heroin, predominant in western US states, may have greater risk for SSTI compared with eastern US powder heroin (Colombian-sourced) due to its association with non-intravenous injection or from possible contamination.. Using nationally representative hospital admissions data from the Nationwide Inpatient Sample and heroin price and purity data from the Drug Enforcement Administration, we looked at rates of hospital admissions for opiate-related SSTI (O-SSTI) between 1993 and 2010. Regression analyses examined associations between O-SSTI and heroin source, form and price.. Hospitalization rates of O-SSTI doubled from 4 to 9 per 100,000 nationally between 1993 and 2010; the increase concentrated among individuals aged 20-40. Heroin market features were strongly associated with changes in the rate of SSTI. Each $100 increase in yearly heroin price-per-gram-pure was associated with a 3% decrease in the rate of heroin-related SSTI admissions. Mexican-sourced-heroin-dominant cities had twice the rate of O-SSTI compared to Colombian-sourced-heroin-dominant cities.. Heroin-related SSTI are increasing and structural factors, including heroin price and source-form, are associated with higher rates of SSTI hospital admissions. Clinical and harm reduction efforts should educate heroin users on local risk factors, e.g., heroin type, promote vein health strategies and provide culturally sensitive treatment services for persons suffering with SSTI.

Topics: Adult; Commerce; Costs and Cost Analysis; Female; Heroin; Heroin Dependence; Hospitalization; Humans; Male; Middle Aged; Narcotics; Soft Tissue Infections; United States; Young Adult

To assess the prevalence of overdose of heroin and risk factors in intravenous drug users(IDUs)in Yunnan Province.. During July-August of 2015, IDUs were recruited from four methadone maintenance treatment(MMT)clinics and two compulsory drug rehabilitation centers in Honghe and Dehong prefectures, Yunnan province. The information about IDUs ' demographic characteristics and drug use history, overdose of heroin in previous12 months and the latest overdose of heroin were collected through face to face questionnaire survey. The factors associated with overdose of heroin were evaluated with logistic regression models.. Of the 340 IDUs surveyed, 85.3%(290/340)were males, the mean age was 37.7±8.7 years, 65.6%(223/340)were Han ethnicity, and 49.4%(167/338)were HIV positive, 22.6%(77/340)reported having used club-related drugs(such as ephedrine, methamphetamine, benzodiazepines and ketamine)in the previous 12 months. Of the 340 IDUs, 41.8%(142/340)had at least one overdose of heroin in their lifetime(median: 3 overdoses)and 15.6%(53/340)had at least one overdose of heroin(median : 1 overdose use)in previous 12 months. The mean age of the 53 IDUs was(36.7 ± 8.4)years, and 83.0%(44/53)of them were males, the average drug use history was(16.5 ± 7.6)years. Dosage increase(26.4%, 14/53)and multidrug use(28.3%, 15/53)were the main causes for overdose of heroin. Multiple logistic regression analysis indicated that methadone maintenance treatment during the past year(OR=0.534, 95%CI: 0.290-0.980)was independently associated with decreased risk of overdose of heroin, needle sharing in the past 6 months(OR=2.735, 95%CI: 1.383-5.407)and being forced to receive drug rehabilitation for less than one year(OR=2.881, 95% CI: 1.226-6.767)were independently associated with increased risk of overdose of heroin.. Overdose of heroin is common among IDUs in Yunnan. It is necessary to encourage IDUs to receive MMT and strengthen the health education about the prevention of overdose of heroin, especially before they leave drug rehabilitation centers. And it is important to establish a referral mechanism from drug rehabilitation center to MMT clinic for drug users.

Topics: China; Drug Overdose; Drug Users; Heroin; Heroin Dependence; HIV Seropositivity; Humans; Logistic Models; Male; Methadone; Needle Sharing; Opiate Substitution Treatment; Prevalence; Referral and Consultation; Risk Factors; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Surveys and Questionnaires

Topics: Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Morphine; Substance Abuse Detection

Autism susceptibility candidate 2 (AUTS2) is a gene associated with autism and mental retardation. Recent studies have suggested an association of the AUTS2 gene with heroin dependence, and reduced AUTS2 gene expression may confer increased susceptibility to heroin dependence. However, the functional role of the AUTS2 protein in regulating enduring neuroadaptations in response to heroin exposure has not been established. Here, we investigated the effects of acute and chronic heroin exposure on AUTS2 mRNA and protein expression in the nucleus accumbens (NAc) and caudate-putamen (CPu) to determine whether changes in AUTS2 expression are associated with heroin-induced locomotor sensitization in mice. Moreover, we explored whether AUST2 knockdown affects heroin-induced locomotor sensitization. AUTS2 mRNA and protein expression in the NAc, but not the CPu, was decreased after chronic heroin (1mg/kg) administration. In the NAc, the expression of heroin-induced locomotor sensitization was enhanced through the lentiviral-AUTS2-shRNA-mediated knockdown of AUTS2, while the overexpression of AUTS2 attenuated the locomotor-stimulant effects of heroin. Together, these results indicate that AUTS2 in the NAc, but not the CPu, suppresses the initiation and expression of heroin-induced behavioral sensitization, suggesting that AUST2 may be a potential target for the treatment of heroin dependence.

Topics: Animals; Caudate Nucleus; Cytoskeletal Proteins; Disease Models, Animal; Gene Knockdown Techniques; Heroin; Heroin Dependence; Male; Mice, Inbred C57BL; Motor Activity; Narcotics; Neuropeptides; Nuclear Proteins; Nucleus Accumbens; Putamen; rac1 GTP-Binding Protein; RNA, Messenger; Transcription Factors

Internationally there is a lack of measurement on the impact of childcare on people who use drugs.. The aim of this article was to longitudinally measure drug use, familial and social status and criminal involvement between parents and nonparents who use heroin and have children in their care.. From 2003 to 2006, 404 participants were recruited to the Research Outcome Study in Ireland Evaluating Drug Treatment Effectiveness (ROSIE) as part of a longitudinal cohort study design. Participants completed the Maudsley Addiction Profile and 88% (n = 356) completed interviews at the 3-year period. One way between groups ANOVA with post hoc tests and backward, stepwise multiple regression were employed for analysis.. At follow-up, parents who had children in their care used heroin (p = .004), illicit methadone (p ≤ .001) and cocaine (p = .024) on fewer days than those who had no children, or those who had children but did not have children in their care. These differences were not observed at intake. Living with someone at intake who used drugs was found to be significantly associated with increased heroin (p ≤ .001), benzodiazepine (p = .039), and tobacco (p = .030) use at 3 years. Furthermore, a change in childcare status to caring for a child was associated with increased cannabis use (p = .025). Conclusion/Importance: While caring for children was associated with reduced heroin use at 3 years, living with a person who used at intake removed this effect, thus indicating that while individual based addiction theories reflected observed outcomes, social network connectedness was more influential.

Topics: Child; Child Care; Cohort Studies; Heroin; Heroin Dependence; Humans; Ireland; Methadone

Topics: Heroin; Heroin Dependence; Humans; Myocardial Infarction; Substance Abuse, Intravenous

We investigated whether variation in the dopamine D2 receptor gene (DRD2) and tri-dimensional personality questionnaire (TPQ) scores could be used to aid adjustment of daily methadone requirements of heroin addicts. DRD2 TaqI B polymorphisms and TPQ scores were determined in 138 male Taiwanese heroin addicts who were receiving methadone treatment. Borderline index (harm avoidance + novelty seeking-reward dependence) was calculated for each subject, and three groups were defined: high (mean from all subjects plus 1 standard deviation, or greater), low (half of the calculated high score, or lower) and medium (all values between the high and low scores).. No significant differences in age (p = 0.60), mean methadone dose (p = 0.75) or borderline index group (p = 0.25) were observed between subjects bearing the B1/B1, B1/B2 and B2/B2 DRD2 TaqI genotypes. Among the individuals with low (≤10), medium (11-20) and high (≥21) borderline index scores, there was a significant difference in mean methadone dose (p = 0.04), but not age (p = 0.90). Further analysis showed that mean methadone dose was significantly higher in subjects with low borderline index scores than in those with high scores (62.5 vs. 47.0 mg/day, p = 0.03). The odds ratio for a daily methadone requirement ≥60 mg (median dose across the 138 subjects) was 2.64-fold greater in the low borderline index group than in the high group (p = 0.04).. Although the DRD2 TaqI B genotype was not associated with methadone use requirements, borderline index was revealed as a potential predictive marker for the adjustment of methadone dosage requirements in heroin addicts.

Topics: Adult; Dose-Response Relationship, Drug; Gene Frequency; Genotype; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Personality; Personality Assessment; Polymorphism, Genetic; Receptors, Dopamine D2; Substance-Related Disorders; Surveys and Questionnaires; Taiwan

In our previous article on the question whether heroin addicts are able to give informed consent voluntarily to research on heroin-assisted treatment, we criticized the ongoing bioethical discussion of a flawed conceptualization of heroin addicts' options. As a participant in this discussion, Edmund Henden defends the conceptualization as sufficient for determining whether heroin addicts are able to give informed consent to the research on heroin-assisted treatment voluntarily. This discussion on research on heroin-assisted treatment seems to go astray in several respects. In his reply to our article Henden maintains some of the biases, such as the necessity of abstinence in recovery, that seem to prevail in addiction research on a more general level as well. These biases run the danger of having implausible ethical implications on stakeholders in addiction research and treatment. In our reply to him, we will further clarify and discuss the importance of describing the relevant issues in plausible terms that do justice to the realities of the cases of informed consent in research on heroin-assisted treatment and also raise a wider issue of the ethics of wording as well as of the narrow scope, or 'tunnel vision', in addiction research as currently conducted.

Topics: Behavior, Addictive; Choice Behavior; Heroin; Heroin Dependence; Humans; Informed Consent; Male

Extended-release naltrexone (XRNT) was developed to overcome poor treatment compliance with oral naltrexone in alcohol and opioid-dependent patients. XRNT injections are registered in the United States and Russia, but not in The Netherlands. However, XRNT can be obtained for individual patients, but it is expensive and not reimbursed by the health insurance.. This study evaluates the support for abstinence oriented treatment among heroin-dependent patients and the acceptability of XRNT injections by heroin-dependent patients and treatment providers in The Netherlands.. A sample of 261 patients in methadone maintenance treatment or heroin assisted treatment and a sample of 188 addiction treatment providers completed specially designed questionnaires.. The current study shows that many patients in opioid maintenance treatment (58%) report a desire to become abstinent from opioids and that 83% of the patients with a desire for abstinence are interested in XRNT. The majority of treatment providers (81%) are willing to support the prescription of XRNT injections in opioid-dependent patients to prevent relapse after detoxification.. The current practice of automatic and indefinite continuation of opioid substitution should therefore be reconsidered. However, XRNT injections are very expensive and currently not reimbursed by the health insurance agencies in The Netherlands and thus not really available to most patients.

Topics: Heroin; Heroin Dependence; Humans; Naltrexone; Netherlands

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

Topics: Adult; Age of Onset; Analgesics, Opioid; Anxiety Disorders; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Retrospective Studies; Risk Factors; Time Factors

Topics: Heroin; Heroin Dependence; Morphine; Morphine Derivatives; Narcotics

Topics: Drug Overdose; Heroin; Heroin Dependence; Humans

Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.. Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT).. Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; p. This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction.

Topics: Adult; Analgesics, Opioid; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Single Nucleotide; Protein Precursors; Receptors, Opioid; Receptors, Opioid, delta

Histone acetylation and other modifications of the chromatin are important regulators of gene expression and may contribute to drug-induced behaviors and neuroplasticity. Inhibition of histone deacetylases (HDAC) activity results in the change of some drug-induced behaviors，however, relatively little is known about the effects of HDAC inhibitors on heroin-seeking behavior. In the present study, male rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, followed by 14 daily 2h extinction session in the operant chamber. After training, the heroin priming (250μg/kg) was introduced for the reinstatement of heroin-seeking behavior. Pretreatment with sodium butyrate (NaB) (200 or 400mg/kg, i.p.), an inhibitor of HDAC, failed to affect heroin self-administration. Additionally，systemic administration of NaB (400mg/kg, i.p.)increased significantly the reinstatement of heroin-seeking induced by heroin priming when NaB administered 12h, but not 6h before the reinstatement test. The same effect was observed after the intracerebroventricular injection of NaB (5μL, 100μg/μL). Moreover, the levels of histone H3 acetylation at lysine 18（H3K18）and H4 acetylation at lysine 5 or lysine 8（H4K5 or H4K8）in the accumbens nucleus core and shell were remarkably increased during the reinstatement and were further strengthened after intracerebroventricular injection of NaB. These results demonstrated that activation of histone acetylation may be involved in the heroin-seeking behavior, and identifying these epigenetic changes will be critical in proposing a novel pharmacological strategy for treating heroin addiction.

Topics: Acetylation; Animals; Butyric Acid; Conditioning, Operant; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Epigenesis, Genetic; Extinction, Psychological; Heroin; Heroin Dependence; Histone Deacetylase Inhibitors; Histone Deacetylases; Histones; Infusions, Intraventricular; Male; Motor Activity; Narcotics; Nucleus Accumbens; Random Allocation; Rats, Sprague-Dawley; Self Administration

Among those with opioid use disorder, heroin use is associated with poorer prognosis relative to use of prescription opioids alone. However, relatively little is known about distinguishing features between those who use heroin relative to those who use prescription opioids. In the present study we evaluated differences in delay discounting in those with opioid use disorder based on primary opioid of use. Delay discounting is associated with a range of negative outcomes and is an important therapeutic target in this population.. Treatment-seeking adults with opioid dependence completed self-report measures including past-month opioid use and the Monetary Choice Questionnaire (Kirby and Marakovic, 1996; Kirby et al., 1999), a measure of delay discounting. Participants were divided into two groups based on whether they used any heroin in the past 30days or only prescription opioids, and delay discounting scores were compared between the groups. Group differences in sociodemographic or clinical variables were included in the analysis as covariates.. Results from a forward stepwise linear regression indicated that heroin use was associated with significantly higher delay discounting (B=-0.99, SE. Adults with opioid dependence who exclusively used prescription opioids had lower delay discounting relative to those who used heroin. This finding contributes further to the literature suggesting that heroin use is associated with greater clinical severity among those with opioid use disorder.

Topics: Adult; Analgesics, Opioid; Cross-Sectional Studies; Delay Discounting; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Opioid-Related Disorders; Prescription Drug Misuse; Self Report; Surveys and Questionnaires; Young Adult

In heroin injectors, there have been a number of outbreaks caused by spore-forming bacteria, causing serious infections such as anthrax or botulism. These are, most likely, caused by injecting contaminated heroin, and our aim was to develop a filter that efficiently removes these bacteria and is also likely to be acceptable for use by people who inject drugs (i.e. quick, simple and not spoil the hit).. A prototype filter was designed and different filter membranes were tested to assess the volume of liquid retained, filtration time and efficiency of the filter at removing bacterial spores. Binding of active ingredients of heroin to different types of membrane filters was determined using a highly sensitive analytical chemistry technique.. Heroin samples that were tested contained up to 580 bacteria per gramme, with the majority being Bacillus spp., which are spore-forming soil bacteria. To remove these bacteria, a prototype filter was designed to fit insulin-type syringes, which are commonly used by people who inject drugs (PWIDs). Efficient filtration of heroin samples was achieved by combining a prefilter to remove particles and a 0.22 μm filter to remove bacterial spores. The most suitable membrane was polyethersulfone (PES). This membrane had the shortest filtration time while efficiently removing bacterial spores. No or negligible amounts of active ingredients in heroin were retained by the PES membrane.. This study successfully produced a prototype filter designed to filter bacterial spores from heroin samples. Scaled up production could produce an effective harm reduction tool, especially during outbreaks such as occurred in Europe in 2009/10 and 2012.

Topics: Bacillus subtilis; Bacteriological Techniques; Drug Contamination; Equipment Design; Filtration; Gram-Positive Bacterial Infections; Harm Reduction; Heroin; Heroin Dependence; Humans; Polymers; Spores, Bacterial; Substance Abuse, Intravenous; Sulfones

Adolescent Cannabis exposure has been hypothesized to act as a gateway to opiate abuse. In order to investigate the role of genetic background in cannabinoid-opiate interactions, we studied the effect of Δ(9) -tetrahydrocannabinol (THC) exposure of adolescent Lewis and Fischer 344 rats on the responsiveness of accumbens shell and core dopamine (DA), as monitored by microdialysis, to THC and heroin at adulthood. Heroin reward and reinstatement by heroin priming were studied by conditioned place preference (CPP) and cognitive and emotional functions by object recognition, Y maze and elevated plus maze paradigms. THC stimulated shell DA in Lewis but not in Fischer 344 rats. Adolescent THC exposure potentiated DA stimulant effects of heroin in the shell and core of Lewis and only in the core of Fischer 344 rats. Control Lewis rats developed stronger CPP to heroin and resistance to extinction compared with Fischer 344 strain. In Lewis rats, THC exposure did not affect heroin CPP but potentiated the effect of heroin priming. In Fischer 344 rats, THC exposure increased heroin CPP and made it resistant to extinction. Lewis rats showed seeking reactions during extinction and hedonic reactions in response to heroin priming. Moreover, adolescent THC exposure affected emotional function only in Lewis rats. These observations suggest that long-term effects of Cannabis exposure on heroin addictive liability and emotionality are dependent on individual genetic background.

Topics: Animals; Behavior, Animal; Cannabinoid Receptor Agonists; Dopamine; Dronabinol; Heroin; Heroin Dependence; Male; Microdialysis; Narcotics; Nucleus Accumbens; Rats; Rats, Inbred F344; Rats, Inbred Lew; Reward; Synaptic Transmission

Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self-administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self-administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence-associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid-induced hyperalgesia and eventually intake escalation.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-2 Receptor Agonists; Adrenergic beta-Antagonists; Animals; Behavior, Animal; Clonidine; Drug-Seeking Behavior; Heroin; Heroin Dependence; Hyperalgesia; Narcotics; Prazosin; Propranolol; Pyrimidines; Rats; Receptors, Corticotropin-Releasing Hormone; Self Administration

Heroin abuse is a significant public health issue and is on the rise because of the unintended consequences of strengthening controls for nonmedical use of prescription pain killers. Included in this trend is an increase in opiate exposed newborns that are particularly vulnerable to a number of negative health outcomes.. After presenting a fully validated liquid chromatography-tandem mass spectrometric method for codeine, morphine, 6-monoacetylmorphine, and meconin, a metabolite of the heroin contaminant noscapine, we compared the outcome of 46 authentic umbilical specimens with the results generated using a previous less sensitive method that did not include meconin. Additionally, we provided a summary of opiate finding from a year-long survey of specimens received into a commercial reference laboratory.. The limits of detection for all 4 compounds were 0.1 ng/g, the limit of quantitation was 0.2 ng/g, and the assay was linear from 0.2 to 10.0 ng/g. Of the 46 comparative specimens, this method improved the identification of heroin exposure from 2 to 5, and the year-long survey identified 86 heroin-exposed newborns with 11 of them identified by the sole identification of meconin.. This study demonstrated that a more sensitive analytical platform and the inclusion of meconin in the opiates assay improved the ability to distinguish between in utero heroin exposure and maternal administration of codeine or morphine.

Topics: Adult; Analgesics, Opioid; Calibration; Chromatography, High Pressure Liquid; Codeine; Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Morphine; Morphine Derivatives; Noscapine; Pregnancy; Quality Control; Reference Standards; Reproducibility of Results; Solid Phase Extraction; Substance Abuse Detection; Tandem Mass Spectrometry; Umbilical Cord

Overdose is a significant cause of death among heroin users. Frequently, other heroin users are present when an overdose occurs, which means the victim's life could be saved. There is a lack of studies that, based on heroin users own stories, examine their views, assessments, and responses to witnessed overdoses.. The study is based on qualitative interviews with thirty-five heroin users who witnessed someone else's overdose.. The heroin users generally had a positive attitude towards assisting peers who had overdosed. A number of factors and circumstances, however, contribute to witnesses often experiencing resistance to or ambivalence about responding. The witness's own high, the difficulty in assessing the seriousness of the situation, an unwillingness to disturb someone else's high, uncertainty about the motive behind the overdose and whether the victim does or does not want assistance as well as fear of police involvement, were common factors that acted as barriers to adequate responses in overdose situations.. The fact that being high makes it difficult to respond to overdoses, using traditional methods, argues for simpler and more effective response techniques. This can include intranasal naloxone programs for heroin users. The findings regarding the uncertainty about the intention of the overdose victim and the sensitivity to the experience of a good high argue for more up-front communication and discussion amongst using peers so that they can make their intentions clear to each other. Issues like this can be addressed in overdose education interventions. Overdose prevention measures also need to address the fact that fear of the police acts as a barrier to call emergency services.

Topics: Adult; Attitude to Health; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Interviews as Topic; Male; Middle Aged; Naloxone; Narcotic Antagonists; Peer Group; Police; Sweden; Young Adult

Previous studies have provided inconsistent evidence that chronic exposure to opioid drugs, including heroin and methadone, may be associated with impairments in executive neuropsychological functioning, specifically cognitive impulsivity. Further, it remains unclear how such impairments may relate of the nature, level and extent of opioid exposure, the presence and severity of opioid dependence, and hazardous behaviours such as injecting.. Participants with histories of illicit heroin use (n = 24), former heroin users stabilized on prescribed methadone (methadone maintenance treatment; MMT) (n = 29), licit opioid prescriptions for chronic pain without history of abuse or dependence (n = 28) and healthy controls (n = 28) were recruited and tested on a task battery that included measures of cognitive impulsivity (Cambridge Gambling Task, CGT), motor impulsivity (Affective Go/NoGo, AGN) and non-planning impulsivity (Stockings of Cambridge, SOC).. Illicit heroin users showed increased motor impulsivity and impaired strategic planning. Additionally, they placed higher bets earlier and risked more on the CGT. Stable MMT participants deliberated longer and placed higher bets earlier on the CGT, but did not risk more. Chronic opioid exposed pain participants did not differ from healthy controls on any measures on any tasks. The identified impairments did not appear to be associated specifically with histories of intravenous drug use, nor with estimates of total opioid exposure.. These data support the hypothesis that different aspects of neuropsychological measures of impulsivity appear to be associated with exposure to different opioids. This could reflect either a neurobehavioural consequence of opioid exposure, or may represent an underlying trait vulnerability to opioid dependence.

Topics: Adolescent; Adult; Analgesics; Executive Function; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Male; Methadone; Opiate Substitution Treatment; Young Adult

Craving is an important issue in substance use disorder. To achieve a better understanding of the cognitive processing systems of craving, the cognitive processes of craving have been considered as two distinct processes. One system, based on rule-based inferences and named explicit cognition, is more conscious and effortful. The other system, based on prior learned association and named implicit cognition, is unconscious and effortless. How explicit and implicit cognitions are associated with heroin use in patients with methadone maintenance treatment (MMT) is not clear. This study aimed to explore the relationship between explicit and implicit cognition and heroin use in patients undergoing MMT.. This study recruited one-hundred forty intravenous heroin users. The participants were invited to provide social-demographic data, the severity of substance dependence and explicit cognition with regard to heroin. Then, participants completed a computerized test to assess implicit cognition with regards to heroin.. This study found that explicit and implicit heroin-related cognitions were associated with the frequency of heroin use. There was an interaction effect between implicit and explicit cognition on the frequency of heroin use. This study also found that higher explicit heroin-related cognition was a risk factor for continuing heroin use.. Both explicit and implicit cognitions were associated with the frequency of heroin use in patients undergoing MMT, but only explicit cognition was associated with whether patients could stop using heroin during MMT. Therefore, the status of heroin use in patients undergoing MMT may be related to different cognitive processes.

Topics: Adult; Age Factors; Age of Onset; Cognition; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Neuropsychological Tests; Opiate Substitution Treatment; Psychiatric Status Rating Scales; Risk Factors; Sex Characteristics

Changes in drug market characteristics have been shown to affect drug use patterns but few studies have examined their impacts on injecting initiation experiences and subsequent patterns of injecting drug use (IDU).. We collected data on self-reported injecting initiation experiences and past-month patterns of IDU from 688 regular heroin and methamphetamine injectors in Melbourne, Australia, who initiated injecting across three different drug market periods (prior to the Australian heroin shortage ('high heroin')/immediately following the shortage ('low heroin')/'contemporary' markets (fluctuating heroin and methamphetamine availability)). We used univariable and multivariable logistic regression to examine the relationship between period of injecting initiation and first drug injected, and multinomial logistic regression for the relationship between period of injecting initiation and current injecting patterns.. 425 participants (62%) reported initiating injecting in the high heroin period, 146 (21%) in the low heroin period, and 117 (17%) in the contemporary period. Participants who initiated injecting during the low heroin period were twice as likely to initiate injecting using a drug other than heroin (AOR: 1.94, 95% CI: 1.27-2.95). The most common patterns of drug use among study participants in the month preceding interview were polydrug use (44%) and primary heroin use (41%). Injecting initiation period was either non-significantly or weakly associated with current drug use pattern, which was more strongly associated with other socio-demographic and drug use characteristics, particularly self-reported drug of choice.. The drug market period in which injecting initiation occurred influenced the first drug injected and influenced some aspects of subsequent drug use. In the context of highly dynamic drug markets in which polydrug use is common there is a need for broad harm reduction and drug treatment services which are flexible and responsive to changing patterns of drug use.

Topics: Adult; Amphetamine-Related Disorders; Data Collection; Female; Harm Reduction; Heroin; Heroin Dependence; Humans; Logistic Models; Male; Methamphetamine; Multivariate Analysis; Substance Abuse, Intravenous; Time Factors; Victoria; Young Adult

Mu-opioid receptors (MOPRs) are the target of heroin and other prescription opioids, which are currently responsible for massive addiction morbidity in the US. The gene coding for the human MOPR (OPRM1) has an important functional single nucleotide polymorphism (SNP), A118G. The OPRM1 A118G genotype results in substantially increased risk of heroin addiction in humans; however, the neurobiological mechanism for this increased risk is not fully understood. This study examined heroin self-administration (SA) behavior in A112G (G/G) mice, harboring a functionally equivalent SNP in Oprm1 with a similar amino acid substitution, in extended (4 h) SA sessions. Adult male and female G/G mice and 'wild-type' litter mates (A/A) were allowed to self-administer heroin (0.25 mg/kg/unit dose, FR1 with a nose poke response) for 4 h/day, for 10 consecutive days. Half of the mice then continued in a heroin dose-response study, while extinction from heroin SA was studied in the other half. In vivo microdialysis was used to measure acute heroin-induced increases of striatal dopamine in the GG vs AA genotypes. Male and female G/G mice responded for heroin significantly more (and thus had greater intake) than A/A mice, in the initial 10 days of heroin SA, and in the subsequent dose-response study. There were no significant differences in extinction of SA between the A/A and G/G mice. Heroin-induced increases in striatal dopamine levels are higher in the GG mice than in the AA mice. Both male and female G/G mice self-administered more heroin than did A/A mice over a 10-day period, possibly because of the greater increases of heroin-induced striatal dopamine in the GG mice. Furthermore, G/G male mice escalated the amount of heroin self-administration across 10 extended-access sessions more than A/A male mice did. These are the first studies to examine the acquisition of heroin SA in this mouse model. These studies may lead to a better understanding of the neurobiological and behavioral mechanisms that underlie greater risk of heroin addiction in carriers of the A118G SNP.

Topics: Animals; Catheters, Indwelling; Corpus Striatum; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Female; Heroin; Heroin Dependence; Male; Mice, Transgenic; Microdialysis; Narcotics; Polymorphism, Single Nucleotide; Receptors, Opioid, mu; Self Administration

The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence.

Topics: Animals; Central Amygdaloid Nucleus; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking Behavior; Drug-Seeking Behavior; Feeding Behavior; Heroin; Heroin Dependence; Locomotion; Male; Narcotics; Orexin Receptor Antagonists; Orexin Receptors; Rats, Wistar; RNA, Messenger; Self Administration; Substance Withdrawal Syndrome; Time Factors

Can heroin addicts give consent to research on trials in which heroin is prescribed to them? Analyses of addicts and informed consent have been objects of debate in several articles. Informed consent requires the agent not only to be competent but also to give consent voluntarily. This has been questioned because of alleged features of heroin addiction. Until recently the discussion has focused on heroin addicts' desires for heroin, whether these are irresistible and thus pose a problem for giving consent. Still, in light of empirical evidence, there seems to be a consensus more or less that the problem is not whether the addicts can resist their desire for heroin. A recent article concentrates specifically on heroin addicts' false assumptions of options and voluntariness. We argue that the prevailing framing of the options in this discussion in terms of heroin and access to it is problematic. The way in which the options are typically laid out suggests an assumption that participation in the research is allegedly based on the addicts' views on using the drug. We argue that this way of presenting the options is, first, a mismatch to the studies carried out and, second, symptomatic of potential misconceptions about heroin addiction and addicts. Furthermore, we also suggest that the account of voluntariness needs to be realistic in order for subjects to be able to give consent voluntarily in actual situations, and for medical research to carry out studies on improving outcomes in addiction treatment in an ethical way.

Topics: Choice Behavior; Heroin; Heroin Dependence; Humans; Informed Consent; Motivation; Personal Autonomy; Volunteers

Between late 2010 and mid 2011 there was a significant heroin shortage in the United Kingdom (UK), resulting in a rapid drop in street heroin purity and increase in price. The most well documented event of this kind is the 2000-2001 Australian heroin shortage, with little published research addressing the UK context. In this paper we draw on qualitative data to explore the impact of, and responses to, the 2010/2011 shortage among London-based heroin users.. Data collection comprised longitudinal life history and narrative interviews with 37 PWID in 2010-2011. The average age of participants was 40, with a 20-year average duration of injecting. Heroin was the drug of choice for the majority of participants (25), with 12 preferring to inject a crack-cocaine and heroin mix. Recruitment took place through London drug and alcohol services and peer networks.. The majority of participants continued to source and inject heroin despite reported decline in purity and increased adulteration. Transitions to poly-drug use during the heroin shortage were also common, increasing vulnerability to overdose and other drug related harms. Participants enacted indigenous harm reduction strategies in attempting to manage changes in drug purity and availability, with variable success.. Epidemiological data gathered during periods of heroin shortage is often drawn on to emphasise the health benefits of reductions in supply. Our findings highlight the importance of understanding the ways in which heroin shortages may increase, as well as reduce, harm. There is a need for enhanced service provision during periods of drug shortage as well as caution in regard to the posited benefits of supply-side drug law enforcement.

Topics: Adult; Cocaine-Related Disorders; Crack Cocaine; Data Collection; Drug Contamination; Drug Overdose; Female; Harm Reduction; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Substance Abuse, Intravenous; United Kingdom; Young Adult

Previous studies that utilized task-based approaches have demonstrated that the chronic use of heroin is associated with altered activity of the anterior cingulate cortex (ACC). However, few studies have focused on examining the variation in resting-state functional connectivity in heroin-dependent individuals, which might help further understanding the mechanisms underlying heroin addiction. Due to the structural and functional heterogeneity of the ACC, we systematically mapped the resting-state functional connectivity patterns of three sub-regions of the ACC in heroin-dependent individuals, wondered whether the partition of three sub-regions of the ACC is feasible in heroin-dependent individuals, and identified how heroin affected the correlated activities among three sub-regions of the ACC using resting-state functional magnetic resonance imaging (fMRI). In the present study, fMRI data were acquired from 21 heroin-dependent individuals (Her group) and 15 non-addicted controls (CN group). Compared to controls, there were reduced functional connectivities in the dorsal ACC (dACC) and rostral ACC (rACC) networks with different areas of the dorsal striatum (the caudate and the putamen) in the Her group. Meanwhile, there exhibited an inverted alteration of pattern for orbital frontal cortex (OFC) and superior frontal gyrus (SFG) in the functional connectivity network with the dACC and subcallosal ACC (sACC), and a different alteration of the cerebellum and the amygdala in the functional connectivity network with the rACC and the sACC. In addition, we also found reduced connectivities between dACC and rACC, as well as reduced connectivities between sACC and dACC. Our findings of variations of functional connectivities in three sub-regions of ACC in Her group implied that these sub-regions of the ACC together with other key brain areas (such as dorsal striatum, OFC, SFG, cerebellum, amygdale, etc.) might potentially play independent and/or overlapping roles in heroin addiction, which might indicate the potential direction of future research.

Topics: Adult; Brain Mapping; Gyrus Cinguli; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Narcotics; Rest

Opiate addiction is a brain disorder emerging through repeated intoxication and withdrawal episodes. Epidemiological studies also indicate that chronic exposure to opiates may lead in susceptible individuals to the emergence of depressive symptoms, strongly contributing to the severity and chronicity of addiction. We recently established a mouse model of heroin abstinence, characterized by the development of depressive-like behaviors following chronic heroin exposure.. While genetic factors regulating immediate behavioral responses to opiates have been largely investigated, little is known about their contribution to long-term emotional regulation during abstinence. Here, we compared locomotor stimulation and physical dependence induced by heroin exposure, as well as emotional dysfunction following abstinence, across mice strains with distinct genetic backgrounds.. Mice from three inbred strains (C57BL/6J, Balb/cByJ, and 129S2/SvPas) were exposed to an escalating chronic heroin regimen (10-50 mg/kg). Independent cohorts were used to assess drug-induced locomotor activity during chronic treatment, naloxone-precipitated withdrawal at the end of chronic treatment, and emotional-like responses after a 4-week abstinence period.. Distinct behavioral profiles were observed across strains during heroin treatment, with no physical dependence and low locomotor stimulation in 129S2/SvPas. In addition, different behavioral impairments developed during abstinence across the three strains, with increased despair-like behavior in 129S2/SvPas and Balb/cByJ, and low sociability in 129S2/SvPas and C57BL/6J.. Our results indicate that depressive-like behaviors emerge during heroin abstinence, whatever the severity of immediate behavioral responses to the drug. In addition, inbred mouse strains will allow studying several aspects of mood-related deficits associated with addiction.

Topics: Animals; Arousal; Emotions; Heroin; Heroin Dependence; Male; Mice; Mice, Inbred Strains; Motor Activity; Naloxone; Social Behavior; Substance Withdrawal Syndrome

To characterize trends in drug abuse in China before and after the 2005 initiation of the 'People's War on Drugs'.. Retrospective self-controlled study.. Annual, nation-wide surveillance from 2003 to 2010 of all registered drug users in China's National Surveillance System on Drug Abuse (NSSDA).. A total of 1,184,124 drug users registered in NSSDA were involved in this study and were classified into three groups based on registered dates-pre-war group (n=230,278) registered 2003-04, phase I group (n=518,651) registered 2005-07 and phase II group (n=435,195) registered 2008-10.. Indicators included proportions of:(i) new and relapsed drug users, (ii) heroin and synthetic drug users among new users, (iii) people aged 35 years or younger and (iv) women. Comparisons were made across groups using annual data to describe temporal trends.. Between 2003 and 2010 the proportion of heroin users decreased by 52.3% and synthetic drugs use increased 860.7% among new users, while a 12.8% decrease in the proportion of heroin users and a 918.8% increase in synthetic drug use in all users was detected. Compared with the pre-war group, the proportion of relapsed users decreased 2.6% and 29.1% in the phase I and phase II groups, respectively, but a significant increase in the proportion of new users was found in phase I (OR=1.24, CI=1.15-1.35, p<0.0001), followed by an apparent decrease in phase II compared with phase I (OR=0.75, CI=0.70-0.80, p<0.0001). Similarly, the proportion of heroin users decreased 15.1 and 24.2% among new drug users in phase I and phase II in comparison with the pre-war group.. The decrease in proportions of drug users in China between 2003/4 and 2008/10 may suggest some positive influence of the 'People's War on Drugs', especially in the decreased proportion of relapsed users. In contrast, there was a rapid increase in new synthetic drug use over the same period.

Topics: Adult; China; Drug Users; Epidemics; Epidemiological Monitoring; Female; Heroin; Heroin Dependence; Humans; Male; Recurrence; Retrospective Studies; Self Report

In this study, an incubation, solid-phase extraction (SPE) and LC-MS-MS procedure was developed, validated and used for simultaneous analysis of amphetamine (AP), methamphetamine (MA), morphine (MOR), codeine (COD), 6-acetylmorphine (6-AM) and 6-acetylcodeine (6-AC) in hair. Hair samples were initially cut into sections, washed with dichloromethane, then sonicated in a methanol-trifluoroacetic acid mixture. The resulting solutions were processed with a SPE procedure before undergoing LC-MS-MS analysis. Mass spectrometric analysis was performed in positive-ion, multiple reactions monitoring (MRM) mode, using appropriate collision energy for each selected precursor ion. The overall protocol, when applied to the analysis of hair (50 mg) samples fortified with 100-10,000 pg/mg of the analytes, was found to achieve 55.5-74.6% recovery of the six analytes with the following analytical parameters: (i) intra- and interday precision/accuracy data for the six analytes in the 1.6-7.6%/-6.0-12.8% and 1.3-6.6%/-6.9-9.3% ranges, respectively; (ii) r(2) > 0.998 for all six analytes and (iii) LOD 2 pg/mg for AP and MA, and 8 pg/mg for MOR, COD, 6-AM and 6-AC; LOQ 10 pg/mg for all six analytes. This method was then utilized to (i) analyze hair samples collected from 86 self-reported drug users and (ii) evaluate the deposition pattern of drugs in head hairs from four female MA and heroin users in a rehabilitation facility. This relatively simple protocol was found superior over the GC-MS methods we have previously developed and utilized in our laboratory for the analysis of these six analytes.

Topics: Amphetamine-Related Disorders; Amphetamines; Calibration; Chromatography, High Pressure Liquid; Female; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Heroin Dependence; Humans; Limit of Detection; Linear Models; Predictive Value of Tests; Reference Standards; Reproducibility of Results; Solid Phase Extraction; Substance Abuse Detection; Tandem Mass Spectrometry

A painful petechial rash developed in a patient after the subcutaneous or intravenous injection of reported black tar heroin. Additional history and the appearance of the skin lesion suggested otherwise.

Topics: Adult; Exanthema; Female; Heroin; Heroin Dependence; Humans; Narcotics; Pain; Skin; Substance Abuse, Intravenous

To determine the long-term mortality, remission, criminality and psychiatric comorbidity during 11 years among heroin-dependent Australians.. Longitudinal cohort study.. Sydney, Australia.. A total of 615 participants were recruited and completed baseline interviews between 2001 and 2002. Participants completed follow-up interviews at 3, 12, 24 and 36 months post-baseline, and again at 11 years post-baseline; 431 (70.1%) of the original 615 participants completed the 11-year follow-up.. Participants were administered the Australian Treatment Outcome Study (ATOS) structured interview, addressing demographics, treatment history, drug use, heroin overdose, criminality, health and mental health at all interviews. Overall, 96.1% of the cohort completed at least one follow-up interview.. At 11 years, 63 participants (10.2%) were deceased. The proportion of participants who reported using heroin in the preceding month decreased significantly from baseline (98.7%) to 36-month follow-up (34.0%; odds ratio = 0.01; 95% confidence interval = 0.00, 0.01) with further reductions evident between 36 months and 11 years (24.8%). However, one in four continued to use heroin at 11 years, and close to one-half (46.6%) were in current treatment. The reduction in current heroin use was accompanied by reductions in risk-taking, crime and injection-related health problems, and improvements in general physical and mental health. The relationship with treatment exposure was varied. Major depression was associated consistently with poorer outcome.. In an 11-year follow-up of patients undergoing treatment for heroin dependence, 10.2% had died and almost half were still in treatment; the proportion still using heroin fell to a quarter, with major depression being a significant predictor of continued use.

Topics: Adult; Cohort Studies; Crime; Depressive Disorder, Major; Diagnosis, Dual (Psychiatry); Drug Overdose; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Mental Health; Needle Sharing; New South Wales; Personality Disorders; Sex Distribution; Substance Abuse, Intravenous; Treatment Outcome

To develop a model for estimating the time delay between last heroin consumption and blood sampling in chronic drug users. Eleven patients, all heroin inhalers undergoing detoxification, were included in the study. Several plasma samples were collected during the detoxification procedure and analyzed for the heroin metabolites 6-acetylmorphine (6AM), morphine (MOR), morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), according to a UHPLC/MSMS method. The general linear mixed model was applied to time-related concentrations and a pragmatic four-step delay estimation approach was proposed based on the simultaneous presence of metabolites in plasma. Validation of the model was carried out using the jackknife technique on the 11 patients, and on a group of 7 test patients. Quadratic equations were derived for all metabolites except 6AM. The interval delay estimation was 2-4 days when only M3G present in plasma, 1-2 days when M6G and M3G were both present, 0-1 day when MOR, M6G and M3G were present and <2 h for all metabolites present. The 'jackknife' correlation between declared and actual estimated delays was 0.90. The overall precision of the delay estimates was 8-9 h. The delay between last heroin consumption and blood sampling in chronic drug users can be satisfactorily predicted from plasma heroin metabolites.

Topics: Adult; Biotransformation; Blood Specimen Collection; Forensic Toxicology; Heroin; Heroin Dependence; Humans; Inhalation Exposure; Linear Models; Middle Aged; Predictive Value of Tests; Substance Abuse Detection; Time Factors

Casually exposing adolescents to prescription opioid agents may escalate to daily use. A trend exists for adolescents using prescription opioid agents to substitute heroin because it is significantly cheaper than pills (approximately half of the cost) and is often more readily available. Additionally, it is more potent than most prescription opioid agents and carries increased risks of overdose and death. Although treatment for substance use disorders has traditionally centered on total abstinence, opioid replacement therapy (ORT) is an option that saves lives and prevents overdose deaths. In the United States, ORT is based on two medicines: methadone and buprenorphine. These drugs can be substituted for other opiate agents and have much lower overdose risks. Nursing implications and web-based resources for teaching are presented.

Topics: Adolescent; Analgesics, Opioid; Drug Overdose; Drug Substitution; Heroin; Heroin Dependence; Humans; Methadone; Nurse-Patient Relations; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; Substance Withdrawal Syndrome; United States

Heroin-associated stroke is a rare complication of use. Various proposed mechanisms of heroin-associated ischemic stroke have been proposed, including the following: cardioembolism in the setting of infective endocarditis, hypoxic ischemic brain injury in the setting of hypoxemia and hypotension, and infective arteritis or vasculitis from drug adulterants. A previously healthy 28-year-old woman presented to the emergency department with altered mental status and normal vitals after she was found wandering outside her apartment. During ambulance transport, she endorsed heroin use. The patient was alert but could not recall her name, place, or time. She intermittently responded "I don't know" to questioning and could not perform simple commands. No motor or sensory deficits were apparent other than sluggish pinpoint pupils. There were no signs of trauma other than antecubital track marks. Her laboratory results were unremarkable. Reevaluation at 2 hours after presentation showed persistent confusion and disorientation. A computed tomographic scan of the head was obtained, which showed a large 5.1 × 5-cm intraparenchymal hemorrhage in the left frontal lobe, vasogenic edema, and a 5-mm midline shift. A workup for cardioembolic, vasculitis, and other etiologies for stroke did not reveal an underlying cause. The patient remained confused with significant memory loss throughout her hospital stay and was eventually discharged to a long-term care facility. Drug abuse should be considered a risk factor for stoke in young adults. In patients with persistent neurologic deficits, physicians must be vigilant and order appropriate workup while managing drug overdose.

Topics: Adult; Cerebral Hemorrhage; Female; Heroin; Heroin Dependence; Humans; Narcotics; Radiography; Stroke

One of the consequences of heroin dependency is a huge expenditure on drugs. This underlying economic expense may be a grave burden for heroin users and may lead to criminal behavior, which is a huge cost to society. The neuropsychological mechanism related to heroin purchase remains unclear. Based on recent findings and the established dopamine hypothesis of addiction, we speculated that expenditure on heroin and central dopamine activity may be associated. A total of 21 heroin users were enrolled in this study. The annual expenditure on heroin was assessed, and the availability of the dopamine transporter (DAT) was assessed by single-photon emission computed tomography (SPECT) using [(99m)TC]TRODAT-1. Parametric and nonparametric correlation analyses indicated that annual expenditure on heroin was significantly and negatively correlated with the availability of striatal DAT. After adjustment for potential confounders, the predictive power of DAT availability was significant. Striatal dopamine function may be associated with opioid purchasing behavior among heroin users, and the cycle of spiraling dysfunction in the dopamine reward system could play a role in this association.

Topics: Adult; Costs and Cost Analysis; Dopamine Plasma Membrane Transport Proteins; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Neostriatum; Tomography, Emission-Computed, Single-Photon

Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.

Topics: Adult; Case-Control Studies; Female; Heroin; Heroin Dependence; Humans; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Tumor Necrosis Factor-alpha

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Methadone

This paper reports estimates of the price elasticity of demand for heroin based on a newly constructed dataset. The dataset has two matched components concerning the same sample of regular heroin users: longitudinal information about real-world heroin demand (actual price and actual quantity at daily intervals for each heroin user in the sample) and experimental information about laboratory heroin demand (elicited by presenting the same heroin users with scenarios in a laboratory setting). Two empirical strategies are used to estimate the price elasticity of demand for heroin. The first strategy exploits the idiosyncratic variation in the price experienced by a heroin user over time that occurs in markets for illegal drugs. The second strategy exploits the experimentally induced variation in price experienced by a heroin user across experimental scenarios. Both empirical strategies result in the estimate that the conditional price elasticity of demand for heroin is approximately -0.80.

Topics: Adult; Commerce; Female; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Middle Aged; United States

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

Topics: Adult; Basal Ganglia; Brain; Brain Mapping; Cross-Over Studies; Double-Blind Method; Female; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Morphine; Opiate Substitution Treatment; Rest; Reward

Little is known about connectivity within the default mode network (DMN) in heroin-dependent individuals (HDIs). In the current study, diffusion-tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were combined to investigate both structural and functional connectivity within the DMN in HDIs.. Fourteen HDIs and 14 controls participated in the study. Structural (path length, tracts count, (fractional anisotropy) FA and (mean diffusivity) MD derived from DTI tractography)and functional (temporal correlation coefficient derived from rs-fMRI) DMN connectivity changes were examined in HDIs. Pearson correlation analysis was performed to compare the structural/functional indices and duration of heroin use/Iowa gambling task(IGT) performance in HDIs.. HDIs had lower FA and higher MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to right parahippocampal gyrus (PHG), compared to the controls. HDIs also had decreased FA and track count in the tract connecting the PCC/PCUN and medial prefrontal cortex (MPFC), as well as decreased functional connectivity between the PCC/PCUN and bilateral PHG and MPFC, compared to controls. FA values for the tract connecting PCC/PCUN to the right PHG and connecting PCC/PCUN to the MPFC were negatively correlated to the duration of heroin use. The temporal correlation coefficients between the PCC/PCUN and the MPFC, and the FA values for the tract connecting the PCC/PCUN to the MPFC were positively correlated to IGT performance in HDIs.. Structural and functional connectivity within the DMN are both disturbed in HDIs. This disturbance progresses as duration of heroin use increases and is related to deficits in decision making in HDIs.

Topics: Adult; Brain; Brain Mapping; Case-Control Studies; Diffusion Tensor Imaging; Gyrus Cinguli; Heroin; Heroin Dependence; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Parahippocampal Gyrus; Radiography

The abnormal cognitive processing of drug cues is a core characteristic of drug dependence. Previous research has suggested that the late positive potential (LPP) of heroin users is increased by heroin-related stimuli because of the attention-grabbing nature of such stimuli.. The present research used a modified emotional Stroop (eStroop) task to examine whether there was an early posterior negativity (EPN) modulation to heroin cues compared with emotional or neutral stimuli in heroin dependent subjects.. Fifteen former heroin users and 15 matched controls performed the eStroop task, which was composed of positive, negative, heroin-related, and neutral pictures with superimposed color squares. Participants responded to the color of the square and not to the picture while behavioral data and event-related potentials were recorded.. There were no significant differences of EPN amplitudes to emotional and neutral stimuli between heroin users and controls. However, heroin users displayed increased EPN modulation for heroin cues, whereas this modulation was absent in controls.. Drug-related cues acquire motivational salience and automatically capture the attention of heroin users at early processing stages, even when engaged in a non-drug-related task. The EPN to heroin cues could represent a novel electrophysiological index with clinical implications for selecting abstinent drug users who are at increased risk of relapse or to evaluate treatment interventions.

Topics: Adult; Attention; Brain; Cues; Emotions; Evoked Potentials; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Photic Stimulation; Reaction Time

Topics: Canada; Harm Reduction; Heroin; Heroin Dependence; Humans; Narcotics; United States

Topics: Administration, Inhalation; Adult; Female; Heroin; Heroin Dependence; Humans; Hydrocephalus; Narcotics; Ventriculoperitoneal Shunt

Heroin's analgesic, euphoric and dependence-producing effects are primarily mediated by the mu opioid receptor (MOR). A single gene, OPRM1, encodes the MOR. The functional polymorphism A(118)G, located in exon 1 of the OPRM1 gene, results in anatomically-specific reductions in MOR expression, which may alter an individual's response to heroin. In prior studies 118G (rare allele) carriers demonstrated significantly greater opioid tolerance, overdose vulnerability, and pain sensitivity than 118AA homozygotes. Those findings suggest OPRM1 genotype may impact characteristics of heroin use.. The present pilot study characterized the impact of OPRM1 genotype (rs1799971, 118G allele carriers vs. 118AA homozygotes) on heroin-use phenotypes associated with heroin dependence severity in a sample of male, Caucasian chronic heroin users (n = 86).. Results indicate that 118G allele carriers reported significantly more heroin use-related consequences and heroin-quit attempts, and were more likely to have sought treatment for their heroin use than 118AA homozygotes.. These preliminary findings, consistent with extant data, illustrate a role for OPRM1 allelic variation on heroin use characteristics, and provide support for considering genotype in heroin treatment and relapse prevention.

Topics: Adult; Alleles; Black or African American; Drug Overdose; Exons; Female; Genetic Carrier Screening; Genetic Predisposition to Disease; Genotype; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Pilot Projects; Polymorphism, Genetic; Receptors, Opioid, mu; Retrospective Studies; White People

Heroin abuse has increased substantially during the past decade in the United States. This study describes trends and demographic shifts of heroin overdoses and heroin-related fatalities in Wisconsin and contrasts these with prescription opioid overdoses.. This study was cross-sectional using databases of emergency department (ED) visits, hospital admissions, and death certificates in Wisconsin, United States, during 2003-2012. Cases were Wisconsin residents treated for heroin or prescription opioid overdose, and residents who died of heroin-related drug poisoning. Primary measurements were rates over time and by geographic region, and rates and rate ratios for selected demographic characteristics.. During 2003-2012, age-adjusted rates of heroin overdoses treated in EDs increased from 1.0 to 7.9/100,000 persons; hospitalized heroin overdoses increased from 0.7 to 3.5/100,000. Whites accounted for 68% of hospitalized heroin overdoses during 2003-2007 but 80% during 2008-2012. Heroin-related deaths were predominantly among urban residents; however, rural fatalities accounted for zero deaths in 2003 but 31 (17%) deaths in 2012. Among patients aged 18-34 years, those hospitalized with heroin overdose were more often men (73.0% versus 54.9%), uninsured (44.2% versus 29.9%), and urban (84.3% versus 73.2%) than those with prescription opioid overdose. Rates of ED visits for heroin overdose in this age group exceeded rates for prescription opioid overdose in 2012 (26.1/100,000 versus 12.6/100,000 persons, respectively).. An epidemic of heroin abuse is characterized by demographic shifts toward whites and rural residents. Rates of heroin overdose in younger persons now exceed rates of prescription opioid overdose.

Topics: Adolescent; Adult; Age Factors; Aged; Analgesics, Opioid; Cross-Sectional Studies; Drug Overdose; Emergency Service, Hospital; Female; Heroin; Heroin Dependence; Hospitalization; Humans; Male; Middle Aged; Rural Population; Sex Factors; Time Factors; Urban Population; Wisconsin; Young Adult

A 40-year-old heroin smoking man presented with acute onset severe shortness of breath. Radiological investigations revealed an unexpected loculated pneumothorax. Respiratory physicians inserted a chest drain which relieved his breathlessness. His exercise tolerance is much improved 6 months on. The side effects of smoking illicit substances are poorly understood. There is a growing trend for drug users to smoke rather than intravenously inject. It is therefore important for clinicians to be aware of the associated morbidity. The authors believe this is the first ever reported case of loculated pneumothorax associated with heroin smoking.

Topics: Administration, Inhalation; Adult; Chest Tubes; Dyspnea; Heroin; Heroin Dependence; Humans; Male; Pneumothorax; Smoking; Treatment Outcome

Vaccines against drugs of abuse have induced antibodies in animals that blocked the biological effects of the drug by sequestering the drug in the blood and preventing it from crossing the blood-brain barrier. Drugs of abuse are too small to induce antibodies and, therefore, require conjugation of drug hapten analogs to a carrier protein. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Previously, we have shown that 1 (MorHap), a heroin/morphine hapten, conjugated to tetanus toxoid (TT) and mixed with liposomes containing monophosphoryl lipid A [L(MPLA)] as adjuvant, partially blocked the antinociceptive effects of heroin in mice. Herein, we extended those findings, demonstrating greatly improved vaccine induced antinociceptive effects up to 3% mean maximal potential effect (%MPE). This was obtained by evaluating the effects of vaccine efficacy of hapten 1 vaccine conjugates with varying hapten densities using two different commonly used carrier proteins, TT and cross-reactive material 197 (CRM197). Immunization of mice with these conjugates mixed with L(MPLA) induced very high anti-1 IgG peak levels of 400-1500 μg/mL that bound to both heroin and its metabolites, 6-acetylmorphine and morphine. Except for the lowest hapten density for each carrier, the antibody titers and affinity were independent of hapten density. The TT carrier based vaccines induced long-lived inhibition of heroin-induced antinociception that correlated with increasing hapten density. The best formulation contained TT with the highest hapten density of ≥30 haptens/TT molecule and induced %MPE of approximately 3% after heroin challenge. In contrast, the best formulation using CRM197 was with intermediate 1 densities (10-15 haptens/CRM197 molecule), but the %MPE was approximately 13%. In addition, the chemical synthesis of 1, the optimization of the conjugation method, and the methods for the accurate quantification of hapten density are described.

Topics: Adjuvants, Immunologic; Analgesics, Opioid; Animals; Antibody Affinity; Bacterial Proteins; Crystallography, X-Ray; Drug Carriers; Female; Haptens; Heroin; Heroin Dependence; Immunization; Immunoglobulin G; Lipid A; Mice, Inbred BALB C; Models, Molecular; Tetanus Toxoid; Vaccines, Conjugate

This is a case report describing a reversal of fentanyl overdose with naloxone nasal spray. The patient was not aware that he overdosed on fentanyl being sold as heroin.. The Veterans Health Administration (VHA) has implemented an initiative to provide education for veterans, their families, friends and significant others about opioid overdose and use of naloxone reversal kits. The Atlanta VA Medical Center adopted this program to reduce the risk of opioid overdose in high risk patients.. Over the past year, we provided educational sessions for 63 veterans and their families. We also prescribed 41 naloxone kits. We have received three reports of opioid overdose reversal with use of naloxone kits prescribed by the Atlanta VA Medical Center.. The authors recommend that public health administrators and policy makers advocate for the implementation of these programs to reduce the rising number of overdose death in the United States and worldwide.

Topics: Buprenorphine, Naloxone Drug Combination; Drug Overdose; Fentanyl; First Aid; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Naloxone; Nasal Sprays; Recurrence; Veterans

The loss of functioning veins (venous sclerosis) is a root cause of suffering for long-term heroin injectors. In addition to perpetual frustration and loss of pleasure/esteem, venous sclerosis leads to myriad medical consequences including skin infections, for example, abscess, and possibly elevated HIV/HCV risks due to injection into larger jugular and femoral veins. The etiology of venous sclerosis is unknown and users' perceptions of cause/meaning unexplored. This commentary stems from our hypothesis that venous sclerosis is causally related to heroin acidity, which varies by heroin source-form and preparation. We report pilot study data on first ever in vivo measurements of heroin pH and as well as qualitative data on users' concerns and perceptions regarding the caustic nature of heroin and its effects. Heroin pH testing in natural settings is feasible and a useful tool for further research. Our preliminary findings, for example, that different heroin source-forms and preparations have a two log difference in acidity, have potentially broad, vital and readily implementable harm reduction implications.

Topics: Acids; Adult; Biomedical Research; Female; Heroin; Heroin Dependence; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Narcotics; Pilot Projects; Sclerosis; Substance Abuse, Intravenous; Vascular Diseases; Veins

While the risk of opioid overdose is widely accepted, the dangers of opioid withdrawal are far less clearly defined. The purpose of this publication is to provide evidence against the erroneous clinical dictum that opioid withdrawal is never life-threatening.. This case report (N = 1) illustrates an unfortunate, common scenario of a man abusing prescription opioids and heroin. His attempt at self-detoxification with buprenorphine-naloxone resulted in life-threatening opioid withdrawal. A detailed account of each day of his withdrawal period was documented by patient and family report and review of all medical records. The patient was contacted three months after hospitalization to verify information and determine progress in treatment and abstinence from drugs and alcohol.. A review of the literature was completed on severe cases of precipitated and spontaneous opioid withdrawal followed by a discussion of the significance as it relates to this case.. Given the widespread use of prescription opioids and opioid maintenance treatment, physicians should be aware of the complications of acute opioid withdrawal and should be equipped to treat these complications.

Topics: Acute Kidney Injury; Administration, Intranasal; Administration, Oral; Administration, Sublingual; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Intensive Care Units; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Prescription Drugs; Rhabdomyolysis; Self Medication; Substance Withdrawal Syndrome; Young Adult

Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

Topics: Administration, Inhalation; Brain; Disease Progression; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Middle Aged; Nervous System Diseases; Singapore

This editorial considers the findings of the systematic review of heroin-assisted treatment, with six different studies from six different countries, published in this issue. The meta-analysis focuses on supervised injected heroin and reports significant crime reduction and an overall cost-effectiveness of treatment. Despite this body of evidence, policy makers remain reluctant to develop this treatment further. The question remains, what else is required to convince policy makers of the value of such treatment for severe and refractory heroin dependence?

Topics: Administrative Personnel; Cost-Benefit Analysis; Heroin; Heroin Dependence; Humans; Methadone

Heroin overdose, more accurately termed 'heroin-related overdose' due to the frequent involvement of other drugs, is the leading cause of mortality among regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater risk of hospital admission for heroin-related overdose (HOD) in the eastern United States where Colombian-sourced powder heroin is sold than in the western US where black 'tar' heroin predominates. (Unick et al., 2014) This paper examines under-researched influences on HOD, both fatal and non-fatal, using data from a qualitative study of injecting drug users of black tar heroin in San Francisco and powder heroin in Philadelphia Data were collected through in-depth, semi-structured interviews carried out in 2012 that were conducted against a background of longer-term participant-observation, ethnographic studies of drug users and dealers in Philadelphia (2007-12) and of users in San Francisco (1994-2007, 2012). Our findings suggest three types of previously unconsidered influences on overdose risk that arise both from structural socio-economic factors and from the physical properties of the heroin source-types: 1) retail market structure including information flow between users; 2) marketing techniques such as branding, free samples and pricing and 3) differences in the physical characteristics of the two major heroin source forms and how they affect injecting techniques and vascular health. Although chosen for their contrasting source-forms, we found that the two cities have contrasting dominant models of drug retailing: San Francisco respondents tended to buy through private dealers and Philadelphia respondents frequented an open-air street market where heroin is branded and free samples are distributed, although each city included both types of drug sales. These market structures and marketing techniques shape the availability of information regarding heroin potency and its dissemination among users who tend to seek out the strongest heroin available on a given day. The physical characteristics of these two source-types, the way they are prepared for injecting and their effects on vein health also differ markedly. The purpose of this paper is to examine some of the unexplored factors that may lead to heroin-related overdose in the United States and to generate hypotheses for further study.

Topics: Anthropology, Cultural; Drug Overdose; Drug Users; Female; Heroin; Heroin Dependence; Humans; Male; Marketing; Philadelphia; Qualitative Research; San Francisco; Substance Abuse, Intravenous

Food restriction augments heroin seeking in chronically food-restricted male rats under withdrawal, an effect not yet examined in female rats. Importantly, women and female rats possess an increased vulnerability to drugs of abuse, which may be mediated by fluctuations in ovarian hormones.. We investigated the role of estradiol and progesterone in augmented heroin seeking in chronically food-restricted female rats, under withdrawal.. Female rats self-administered heroin for 10-12 days and were then allowed unrestricted (sated) or restricted access to food (FDR; ∼10 % reduction in body weight) for 14 days. On day 14, rats underwent a heroin-seeking test. Exp. 1: Rats underwent ovariectomy or sham surgery and were treated with a low dose of estradiol (5.0 % in cholesterol; subcutaneous capsule). Exp. 2: Rats underwent ovariectomy and were administered with a high dose of estradiol (0.5 mg/kg; subcutaneous) for 8 days before testing. Exp. 3: Progesterone injections (2.0 mg/kg; subcutaneous) were administered 24 h and 2 h before testing.. Food restriction resulted in augmented heroin seeking, compared to sated controls. While ovariectomy had no effect, estradiol replacement attenuated the food restriction effect. Injections of progesterone had no effect on heroin seeking in either the sated or FDR groups.. The effect of food restriction on heroin seeking in female rats under withdrawal is as robust as previously found in males. Interestingly, estradiol replacement, but not progesterone, attenuates the food restriction effect in the ovariectomized rats, possibly due to its anorexic properties.

Topics: Animals; Estradiol; Female; Food Deprivation; Heroin; Heroin Dependence; Ovariectomy; Ovary; Progesterone; Rats; Self Administration

The study evaluates the suitability of a specific immunoassay screening test for 6-acetylmorphine (6-AM) in the setting of suspected very recent heroin consumption for forensic and clinical purposes.. The EMIT® II Plus 6-AM immunoassay was applied in 65 cases that had already tested positive for morphine in urine or blood. Biological samples (n.65 urine and n.53 blood) were obtained from workplace drug tests (WDT n. 5), tests for driving under the influence of drugs (DUID n. 30), vehicle accidents (n. 10), overdoses (n. 12) and heroin-related deaths (n. 8) cases. The 6-AM screening assay results were confirmed with the LC-MS/MS analysis in relation to the cut-off set at 10 ng/mL for both urine and blood.. Among the 65 urine samples (all morphine-positive), 38 samples were 6-AM-positive and 27 were 6-AM-negative with 100% agreement between the positive/negative results of the two assays. Among the 53 blood samples (34 positive and 19 negative for the morphine), 16 were 6-AM positive and 37 were negative. Only one of the blood samples, positive for 6-AM by LC-MS/MS at 10.3 ng/mL, was negative by the immunoassay test. Based on the concordance between the results of the 6-AM immunoassay versus the LC-MS/MS, the sensitivity of the 6-AM assay was calculated as 100% and 95% for urine and blood respectively, with a specificity and accuracy of 100% for both biological samples. In addition, the study demonstrated that the 6-AM assay test, originally developed for urine, is also sufficiently sensitive to identify 6-AM in blood. Therefore, it could be applied in cases of vehicle accidents or overdose to distinguish rapidly between very recent heroin use and the intake of other opiates for therapeutic purposes.

Topics: Driving Under the Influence; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Immunoassay; Male; Morphine Derivatives; ROC Curve; Substance Abuse Detection; Tandem Mass Spectrometry

Topics: Forensic Sciences; Guidelines as Topic; Heroin; Heroin Dependence; History, 20th Century; Human Experimentation; Humans; Poisons; Risk Assessment; United States; United States Department of Agriculture

Topics: Administration, Intranasal; Administration, Oral; Adrenal Cortex Hormones; Adult; Asthma; Disease Progression; Heroin; Heroin Dependence; Humans; Male; Severity of Illness Index

Topics: Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Substance Abuse, Intravenous; Vascular Diseases

Heroin injection is emerging as a significant dimension of the HIV epidemic in Kenya. Preventing transitions to injecting drug use from less harmful forms of use, such as smoking, is a potentially important focus for HIV prevention. There is, however, little evidence to support comprehensive programming in this area, linked to a shortage of analysis of the social and structural context for transitions, particularly in low-income settings. We explore accounts of transitions from smoking to injecting in Kenya to understand the role of individual, social and structural processes.. We combine data from two separate studies conducted in Kenya: an in-depth qualitative study of HIV care access for people who inject drugs (study 1) and an ethnographic study of the political economy of the heroin trade in Kenya (study 2). In-depth interviews with PWID and community observation from study 1 are triangulated with accounts from stakeholders involved in the heroin trade and documentary data from study 2.. People who inject drugs link transitions to injecting from smoking to a range of social and behavioural factors, as well as particular aspects of the local drug supply and economy. We present these results in the form of two narratives that account for factors shaping transitions. A dominant narrative of 'managing markets and maintaining a high' results from a process of trying to manage poverty and a shifting heroin supply, in the context of deepening addiction to heroin. A secondary narrative focuses on people's curiosity for the 'feeling' of injecting, and the potential pleasure from it, with less emphasis on structural circumstances.. The narratives we describe represent pathways through which structural and social factors interact with individual experiences of addiction to increase the risk of transitions to injecting. In response, HIV and harm reduction programmes need combinations of different strategies to respond to varied experiences of transitions. These strategies should include, alongside behaviour-oriented interventions, structural interventions to address economic vulnerability and the policing of the drug supply.

Topics: Adult; Comorbidity; Drug Users; Female; Harm Reduction; Heroin; Heroin Dependence; HIV Infections; Humans; Interviews as Topic; Kenya; Male; Middle Aged; Qualitative Research; Substance Abuse, Intravenous; Young Adult

In contrast to research on more restricted samples of drug users, epidemiological studies open up a view of death rates and survivorship of those who have tried heroin a few times, with no acceleration toward sustained use patterns often seen in treatment and criminal justice samples. At their best, epidemiological estimates of heroin effects on risk of dying are not subject to serious selection biases faced with more restricted samples.. Data are from 7207 adult participants aged 18-48 years in United States Epidemiologic Catchment Area Program field surveys, launched in 1980-1984. US National Death Index (NDI) records through 2007 disclosed 723 deaths. NDI enabled estimation of heroin-associated risk of dying as well as survivorship.. Estimated cumulative mortality for all 18-48 year old participants is 3.9 deaths per 1000 person-years (95% confidence interval, CI=3.7, 4.2), relative to 12.4 deaths per 1000 person-years for heroin users (95% CI=8.7, 17.9). Heroin use, even when non-sustained, predicted a 3-4 fold excess of risk of dying prematurely. Post-estimation record review showed trauma and infections as top-ranked causes of these deaths.. Drawing strengths from epidemiological sampling, standardized baseline heroin history assessments, and very long-term NDI follow-up, this study of community-dwelling heroin users may help clinicians and public health officials who need facts about heroin when they seek to prevent and control heroin outbreaks. Heroin use, even when sporadic or non-sustained, is predictive of premature death in the US, with expected causes of death such as trauma and infections.

Topics: Adolescent; Adult; Drug Users; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Logistic Models; Male; Middle Aged; Mortality, Premature; Public Health; Risk; Substance-Related Disorders; Survival Rate; United States; Young Adult

Because the role of dopamine (DA) D3 receptors has been investigated primarily in relation to cocaine-related behaviors little is known of the role of these receptors in heroin seeking.. To investigate the effect of the selective DA D3 receptor antagonist, SR 21502, on cue-induced reinstatement of heroin seeking and heroin conditioned place preference (CPP).. In experiment 1, rats were trained to self-administer intravenous heroin for 15 days followed by extinction. Following extinction animals were treated with one of several SR 21502 doses (0, 7.5, 10 or 15mg/kg) and a cue-induced reinstatement test was conducted. In experiment 2, animals were conditioned to experience heroin in one compartment of a CPP apparatus and saline in the other. On the test day animals were treated with 0, 3.75, 7.5, 10 or 15mg/kg of SR 21502 and tested for their CPP.. The results from experiment 1 showed a significant dose-related reduction in cue-induced reinstatement of active lever pressing in the 7.5 and 10mg groups and an absence of the reinstatement effect in the 15mg group. In experiment 2, animals treated with vehicle or 3.75mg of SR 21502 showed significant heroin place preferences but those treated with the higher doses showed no CPP.. Our findings suggest that DA D3 receptors play a significant role in heroin approach behaviors driven by conditioned stimuli. As such, we propose that SR 21502 holds potential as an effective pharmacotherapeutic agent for relapse prevention and should be studied further.

Topics: Animals; Conditioning, Classical; Cues; Disease Models, Animal; Dose-Response Relationship, Drug; Extinction, Psychological; Female; Heroin; Heroin Dependence; Imidazoles; Male; Pyridines; Rats; Rats, Long-Evans; Receptors, Dopamine D3; Recurrence; Self Administration; Substance Abuse, Intravenous

To observe the expression of discs large homolog 4 (DLG4) protein in hippocampus, amygdala and frontal cortex of rats and evaluate postsynaptic density in heroin dependence.. The rat heroin dependent model was established by increasing intraperitoneal injection of heroin. DLG4 proteins in hippocampus, amygdala and frontal cortex of heroin dependent 9, 18, 36 days rats were detected with immunohistochemical staining and compared with that in the control group.. DLG4 proteins in hippocampus, amygdala and frontal cortex were gradually reduced with extension of heroin dependent time.. Heroin dependence can affect postsynaptic density of hippocampus, amygdala and frontal cortex. The changes become more apparent with extension of heroin dependence time.

Topics: Amygdala; Animals; Disks Large Homolog 4 Protein; Frontal Lobe; Heroin; Heroin Dependence; Hippocampus; Injections, Intraperitoneal; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Rats

Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.

Topics: Administration, Oral; Adult; Analgesics, Opioid; Capnography; Drug Overdose; Electromyography; Female; Heroin; Heroin Dependence; Humans; Hypoventilation; Injections, Intramuscular; Male; Methadone; Middle Aged; Morphine; Oximetry; Pulmonary Disease, Chronic Obstructive

Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.

Topics: Animals; Behavior, Addictive; Drug-Seeking Behavior; Gene Expression; Heroin; Heroin Dependence; Hippocampus; Intracellular Signaling Peptides and Proteins; Male; Motivation; Narcotics; Nucleus Accumbens; Prefrontal Cortex; Rats, Sprague-Dawley; Receptors, Dopamine D2; Receptors, G-Protein-Coupled; Reward; Self Administration

We report on patterns and correlates of sustained abstinence at the 11-year follow-up of the Australian Treatment Outcome Study cohort.. This report is a longitudinal cohort analysis of patterns of recent and sustained abstinence.. A total of 431 (70.1%) of the original 615 participants were interviewed, and 10.2% were deceased. The mean elapsed time since heroin initiation was 20.4 years (SD = 7.2). At the 11-year follow-up, heroin abstinence over the preceding month was reported by 75.2%. A period of at least 1 month's abstinence across the follow-up was reported by 97.7% and at least 1 year by 89.9%, whereas 52.2% reported an abstinence period of 5 or more consecutive years. Sustained abstinence across the entire follow-up period was reported by 5.6%. Independent correlates of 5 or more consecutive years of heroin abstinence were female gender (odds ratio [OR] = 1.73), not being currently enrolled in a drug treatment program (OR = 2.16), and fewer treatment episodes across the follow-up (OR = 0.90, 95% CI [0.85, 0.96]).. The clinical profile of the cohort at the 11-year follow-up was encouraging, with the majority currently heroin abstinent, a proportion that has increased across time. Although only a small minority maintained abstinence over the entire period, half had sustained abstinence for at least 5 consecutive years. With the exception of gender, baseline characteristics made poor predictors of long-term abstinence. Treatment stability, however, appears crucial in maintaining abstinence.

Topics: Adult; Aged; Australia; Cohort Studies; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Treatment Outcome

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer.

Topics: Adult; Delay Discounting; Emotional Intelligence; Female; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Intelligence; Male; Middle Aged; Reward; Substance Withdrawal Syndrome; Young Adult

Topics: Female; Heroin; Heroin Dependence; Humans; Hydrocephalus; Narcotics

Topics: Acute Disease; Adult; Compartment Syndromes; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male

Topics: Female; Heroin; Heroin Dependence; Humans; Hydrocephalus; Narcotics

Heroin is one of the most dangerous drugs of abuse, which may exert various neurotoxic actions on the brain (such as gray matter loss, neuronal apoptosis, mitochondrial dysfunction, synaptic defects, depression of adult neurogenensis, as well as development of spongiform leucoencephalopathy). Some of these toxic effects are probably mediated by the gas nitric oxide (NO). We studied by morphometric analysis the numerical density of neurons expressing neuronal nitric oxide synthase (nNOS) in cortical and hypothalamic areas of eight heroin overdose victims and nine matched controls. Heroin addicts showed significantly increased numerical densities of nNOS immunoreactive cells in the right temporal cortex and the left paraventricular nucleus. Remarkably, in heroin abusers, but not in controls, we observed not only immunostained interneurons, but also cortical pyramidal cells. Given that increased cellular expression of nNOS was accompanied by elevated NO generation in brains of heroin addicts, these elevated levels of NO might have contributed to some of the known toxic effects of heroin (for example, reduced adult neurogenesis, mitochondrial pathology or disturbances in synaptic functioning).

Topics: Adolescent; Adult; Case-Control Studies; Drug Overdose; Female; Glutamate Decarboxylase; Glutamate-Ammonia Ligase; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Nitric Oxide Synthase; Paraventricular Hypothalamic Nucleus; Temporal Lobe

It is well established that re-exposure to a context paired with the effects of drugs of abuse can renew extinguished drug seeking behavior. A context, however, typically includes several stimuli, which may differ in their ability to control drug-oriented behaviors. Hence, the primary objective of this study was to assess whether a heroin-induced place preference could be recovered by re-exposure to a contextual stimulus that was part of the conditioning context before extinction. The second objective was to explore the role of the basolateral nucleus of the amygdala (BLA) in this conditioned effect. Male Sprague-Dawley rats were injected with 3 mg/kg heroin and confined in a compartment that was distinguished by a variety of contextual stimuli, including a ceramic floor tile. During extinction, the floor stimulus was removed, and it was reintroduced for a drug-free test of preference. A control experiment evaluated the unconditioned preference for the floor stimulus. It was found that reintroduction of the floor stimulus caused the recovery of heroin place preference. This effect was not observed in rats infused in the BLA with muscimol (0.03 nmol) and baclofen (0.3 nmol) just prior to the test. These data suggest that an extinguished heroin place preference can be renewed by a contextual tactual stimulus that was part of the conditioning context, and that this process requires an intact BLA.

Topics: Amygdala; Analysis of Variance; Animals; Baclofen; Conditioning, Psychological; Cues; Extinction, Psychological; GABA-A Receptor Agonists; GABA-B Receptor Agonists; Heroin; Heroin Dependence; Male; Muscimol; Narcotics; Rats; Rats, Sprague-Dawley; Space Perception; Time Factors

Topics: Canada; Clinical Trials as Topic; Heroin; Heroin Dependence; Humans; Hydromorphone; Narcotics; Therapeutic Human Experimentation

Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 ("true") specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine.

Topics: Animals; Antibody Specificity; Cross Reactions; Female; Haptens; Heroin; Heroin Dependence; Lipid A; Liposomes; Mice; Mice, Inbred BALB C; Morphine; Morphine Derivatives; Nociception; Vaccines

The aim of this paper is to illustrate how Switzerland was able to play such a pioneering role in the field of addiction treatment, in creating a drug policy that includes the medical prescription of diacetylmorphine (heroin). The paper will also describe the role of knowledge brokering processes and coalition building in the different phases of the development of the Swiss drug policy.. The medical prescription of diacetylmorphine was the exotic element of the Swiss drug policy of 1991 and probably still is one of the most controversial practices in clinical medicine despite its documented effectiveness. Coalitions of change actors, across stakeholder groups from many professions and politicians on various levels, succeeded in formulating and starting initiatives for a new drug policy and its innovations. Clear, shared objectives and a common feeling of urgency brought the coalitions together.. In the case of Switzerland, the Confederation took a leading role by facilitating communication, encouraging scientific knowledge and bringing the various stakeholders on a platform to deliver a consensual political policymaking basis. This was facilitated by the Swiss direct democracy system. Sustained dialogue between researchers and the users of research enhances the likelihood of research affecting policy.

Topics: Harm Reduction; Health Policy; Heroin; Heroin Dependence; Humans; Maintenance Chemotherapy; Narcotics; Opiate Substitution Treatment; Switzerland; Treatment Outcome

Active immunization is an effective means of blocking the pharmacodynamic effects of drugs and holds promise as a treatment for heroin addiction. Previously, we demonstrated the efficacy of our first-generation vaccine in blocking heroin self-administration in rats, however, many vaccine components can be modified to further improve performance. Herein we examine the effects of varying heroin vaccine injection route and adjuvant formulation. Mice immunized via subcutaneous (sc) injection exhibited inferior anti-heroin titers compared to intraperitoneal (ip) and sc/ip coadministration injection routes. Addition of TLR9 agonist cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) to the original alum adjuvant elicited superior antibody titers and opioid affinities compared to alum alone. To thoroughly assess vaccine efficacy, full dose-response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests. Mice treated with CpG ODN 1826 exhibited greatly shifted dose-response curves (10-13-fold vs unvaccinated controls) while non-CpG ODN vaccine groups did not exhibit the same robust effect (2-7-fold shift for ip and combo, 2-3-fold shift for sc). Our results suggest that CpG ODN 1826 is a highly potent adjuvant, and injection routes should be considered for development of small molecule-protein conjugate vaccines. Lastly, this study has established a new standard for assessing drugs of abuse vaccines, wherein a full dose-response curve should be performed in an appropriate behavioral task.

Topics: Adjuvants, Immunologic; Alum Compounds; Analgesics; Animals; Antibodies; Drug Administration Routes; Enzyme-Linked Immunosorbent Assay; Heroin; Heroin Dependence; Immunization; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Male; Mice; Oligodeoxyribonucleotides; Rats; Toll-Like Receptor 9; Vaccines, Conjugate

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Outcome Assessment, Health Care

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Outcome Assessment, Health Care

To investigate frequent findings in cases of fatal opioid intoxication in whole-body post-mortem computed tomography (PMCT).. PMCT of 55 cases in which heroin and/or methadone had been found responsible for death were retrospectively evaluated (study group), and were compared with PMCT images of an age- and sex-matched control group. Imaging results were compared with conventional autopsy.. The most common findings in the study group were: pulmonary oedema (95 %), aspiration (66 %), distended urinary bladder (42 %), cerebral oedema (49 %), pulmonary emphysema (38 %) and fatty liver disease (36 %). These PMCT findings occurred significantly more often in the study group than in the control group (p < 0.05). The combination of lung oedema, brain oedema and distended urinary bladder was seen in 26 % of the cases in the study group but never in the control group (0 %). This triad, as indicator of opioid-related deaths, had a specificity of 100 %, as confirmed by autopsy and toxicological analysis.. Frequent findings in cases of fatal opioid intoxication were demonstrated. The triad of brain oedema, lung oedema and a distended urinary bladder on PMCT was highly specific for drug-associated cases of death.. Frequent findings in cases of fatal opioid intoxication were investigated. Lung oedema, brain oedema and full urinary bladder represent a highly specific constellation. This combination of findings in post-mortem CT should raise suspicion of intoxication.

Topics: Adolescent; Adult; Autopsy; Brain Edema; Cardiomegaly; Cause of Death; Female; Forensic Pathology; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Pulmonary Edema; Retrospective Studies; Sensitivity and Specificity; Tomography, X-Ray Computed; Urinary Bladder; Whole Body Imaging; Young Adult

It has been proposed that relapse vulnerability in previously dependent individuals results from augmentation of drug-induced reinforcement due to repeated associations between the interoceptive properties of the drug and reduction of acute withdrawal distress.. To test this hypothesis, male Sprague-Dawley rats self-administered 0.05 mg/kg/inf heroin on continuous reinforcement (CR) and progressive ratio (PR) schedules. During this period, they also received injections of vehicle or escalating doses of heroin. Following tests of naloxone-precipitated withdrawal, as well as a drug-free period (4 days), and extinction (9 sessions), they were pre-treated with vehicle or yohimbine (0.5mg/kg, IV) and tested for resumption of heroin self-administration (0.05 mg/kg/inf) on CR and PR schedules, or tested for reinstatement in extinction conditions.. Increased self-administration on the CR schedule was observed in the heroin-injected rats, but no group differences were observed on the PR schedule, in spite of greater signs of withdrawal precipitated by naloxone in the heroin-injected rats. More importantly, there were no group differences in resumption of heroin self-administration, and this was not altered by yohimbine.. These results suggest that relapse vulnerability cannot be uniquely ascribed to enhanced reinforcing action of drugs; contextual and other conditioning factors must play a role in modulating resumption of drug intake after abstinence.

Topics: Animals; Dose-Response Relationship, Drug; Extinction, Psychological; Heroin; Heroin Dependence; Male; Naloxone; Rats; Reinforcement Schedule; Self Administration; Substance Withdrawal Syndrome; Yohimbine

Dominant public health and medical discourse has relied on a pharmacocentric conception of heroin use-that is, the notion that heroin users inject compulsively to stave off physical and psychological withdrawal. Previous research disputes this claim suggesting that other patterns of heroin use, such as occasional, recreational, or controlled use are possible. In our previous cross-sectional epidemiological research, we identified the phenomenon of low frequency heroin injection (low-FHI), among street-based drug users. The goal of the current study was to qualitatively assess and contextualise this phenomenon over time among a sample of street-based low-FHI.. 29 low-FHI and 25 high frequency heroin injectors (high-FHI) were followed for 2 years, during which they participated in a series of in-depth interviews. Qualitative data were coded using an inductive analysis approach. As similarities and differences between participants were discovered, transcripts were queried for supportive quotations as well as negative cases.. We found the social context among low-FHI and high-FHI to be similar with the exception of their patterns of heroin use. Thus, we focused this analysis on understanding motivations for and management of low-FHI. Two major categories of low-FHI emerged from the data: maintenance and transitioning low-FHI. Maintenance low-FHI sustained low-FHI over time. Some of these heroin users were circumstantial low-FHI, who maintained low-FHI as a result of their social networks or life events, and others maintained low-FHI purposefully. Transitioning low-FHI did not sustain low use throughout the study. We found that heroin use patterns frequently shift over time and these categories help identify factors impacting drug use within particular moments in an individual's life.. Given the various patterns of heroin use that were identified in this study, when working with IDUs, one must assess the specifics of heroin use patterns including drug preferences, desire for substance abuse treatment, as well as basic physical and mental health care needs.

Topics: Adult; Data Collection; Drug Users; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Middle Aged; Motivation; Poverty; Substance Abuse, Intravenous; Time Factors; Urban Population

Immunotherapy against drugs of abuse is being studied as an alternative treatment option in addiction medicine and is based on antibodies sequestering the drug in the bloodstream and blocking its entry into the brain. Producing an efficient vaccine against heroin has been considered particularly challenging because of the rapid metabolism of heroin to multiple psychoactive molecules. We have previously reported that heroin's first metabolite, 6-monoacetylmorphine (6-MAM), is the predominant mediator for heroin's acute behavioral effects and that heroin is metabolized to 6-MAM primarily prior to brain entry. On this basis, we hypothesized that antibody sequestration of 6-MAM is sufficient to impair heroin-induced effects and therefore examined the effects of a monoclonal antibody (mAb) specific for 6-MAM. In vitro experiments in human and rat blood revealed that the antibody was able to bind 6-MAM and block the metabolism to morphine almost completely, whereas the conversion of heroin to 6-MAM remained unaffected. Mice pretreated with the mAb toward 6-MAM displayed a reduction in heroin-induced locomotor activity that corresponded closely to the reduction in brain 6-MAM levels. Intraperitoneal and intravenous administration of the anti-6-MAM mAb gave equivalent protection against heroin effects, and the mAb was estimated to have a functional half-life of 8 to 9 days in mice. Our study implies that an antibody against 6-MAM is effective in counteracting heroin effects.

Topics: Adult; Animals; Antibodies, Monoclonal; Binding Sites; Brain; Heroin; Heroin Dependence; Humans; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Morphine Derivatives; Motor Activity; Rats; Rats, Sprague-Dawley; Tissue Distribution

Transport across the BBB is a determinant of the rate and extent of drug distribution in the brain. Heroin exerts its effects through its principal metabolites 6-monoacetyl-morphine (6-MAM) and morphine. Morphine is a known substrate of P-glycoprotein (P-gp) at the blood-brain-barrier (BBB) however, little is known about the interaction of heroin and 6-MAM with P-gp.. The objective of this paper is to study the role of the P-gp-mediated efflux at the BBB in the behavioral and molecular effects of heroin and morphine.. The transport rates of heroin and its main metabolites, at the BBB, were measured in mice by in situ brain perfusion. We then examined the effect of inhibition of P-gp on the acute nociception, locomotor activity, and gene expression modulations induced by heroin and morphine. The effect of P-gp inhibition during the acquisition of morphine-induced place preference was also studied.. Inhibition of P-gp significantly increased the uptake of morphine but not that of heroin nor 6-MAM. Inhibition of P-gp significantly increased morphine-induced acute analgesia and locomotor activity but did not affect the behavioral effects of heroin; in addition, acute transcriptional responses to morphine were selectively modulated in the nucleus accumbens. Increasing morphine uptake by the brain significantly increased its reinforcing properties in the place preference paradigm.. The present study demonstrated that acute inhibition of P-gp not only modulates morphine-induced behavioral effects but also its transcriptional effects and reinforcing properties. This suggests that, in the case of morphine, transport across the BBB is critical for the development of dependence.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Behavior, Animal; Blood-Brain Barrier; Conditioning, Operant; Cyclosporins; Gene Expression; Heroin; Heroin Dependence; Male; Mice; Morphine; Morphine Derivatives; Motor Activity; Narcotics; Nociception; Nucleus Accumbens; Pain Measurement; Transcription, Genetic

Reducing the enduring vulnerability to relapse is a therapeutic goal in treating drug addiction. Studies with animal models of drug addiction show a marked increase in extrasynaptic glutamate in the core subcompartment of the nucleus accumbens (NAcore) during reinstated drug seeking. However, the synaptic mechanisms linking drug-induced changes in extrasynaptic glutamate to relapse are poorly understood. Here, we discovered impaired glutamate elimination in rats extinguished from heroin self-administration that leads to spillover of synaptically released glutamate into the nonsynaptic extracellular space in NAcore and investigated whether restoration of glutamate transport prevented reinstated heroin seeking. Through multiple functional assays of glutamate uptake and analyzing NMDA receptor-mediated currents, we show that heroin self-administration produced long-lasting downregulation of glutamate uptake and surface expression of the transporter GLT-1. This downregulation was associated with spillover of synaptic glutamate to extrasynaptic NMDA receptors within the NAcore. Ceftriaxone restored glutamate uptake and prevented synaptic glutamate spillover and cue-induced heroin seeking. Ceftriaxone-induced inhibition of reinstated heroin seeking was blocked by morpholino-antisense targeting GLT-1 synthesis. These data reveal that the synaptic glutamate spillover in the NAcore results from reduced glutamate transport and is a critical pathophysiological mechanism underling reinstated drug seeking in rats extinguished from heroin self-administration.

Topics: Animals; Aspartic Acid; Ceftriaxone; Conditioning, Operant; Disease Models, Animal; Down-Regulation; Drug-Seeking Behavior; Excitatory Postsynaptic Potentials; Glutamic Acid; Heroin; Heroin Dependence; In Vitro Techniques; Male; Morpholinos; Neurons; Nucleus Accumbens; Potassium; Rats; Rats, Sprague-Dawley; Secondary Prevention; Synapses

Topics: Health Resources; Heroin; Heroin Dependence; Humans; Nursing Homes; Opiate Substitution Treatment; Patient Care Team; Rehabilitation Centers; Substance Withdrawal Syndrome; Switzerland

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of opiate addiction. Both increased and decreased serum BDNF levels have been reported in heroin addicts. Moreover, the role of BDNF in heroin-dependent patients during withdrawal has not been studied. This study aimed to explore the differences in serum BDNF levels of heroin addicts and healthy controls, and investigate the changes of serum BDNF levels in heroin addicts at baseline and at one month after heroin cessation. Seventy-two heroin-dependent patients and ninety age- and gender-matched healthy controls were enrolled in this study. We measured serum BDNF levels at baseline (both heroin addicts and healthy controls) and one month after heroin cessation (heroin addicts only). A total of 37 (51.4%) heroin addicts completed the one-month study. We found that baseline serum BDNF levels were significantly higher in heroin addicts compared to controls (F=36.5, p=0.001). There was no difference in serum BDNF levels among heroin addicts at baseline and one month after heroin cessation (F=1.101, p=0.301). These results indicate that BDNF may play a critical role in the course of opiate addiction and withdrawal.

Topics: Adult; Brain-Derived Neurotrophic Factor; Case-Control Studies; Female; Heroin; Heroin Dependence; Humans; Male; Substance Withdrawal Syndrome

Inhibition of phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP) increases intracellular cAMP/cAMP-response element binding protein (CREB) signaling. Activation of this signaling is considered as an important compensatory response that decreases motivational properties of drugs of abuse. However, it is not known whether PDE4 is involved in heroin seeking. Self-administration of heroin (50 μg/kg/infusion) was performed under the fixed ratio 1 (FR1) schedule for 14 d and then drug seeking was extinguished for 10 d. The progressive ratio schedule was used to evaluate the relative motivational value of heroin reinforcement. After training, the conditioned cue or heroin priming (250 μg/kg) was introduced for the reinstatement of heroin-seeking behavior. Pretreatment (i.p.) with rolipram (0.03-0.3 mg/kg), a prototypical, selective PDE4 inhibitor, failed to inhibit heroin self-administration under the FR1 schedule, but decreased the reward values under the progressive ratio schedule in a dose-dependent manner. In addition, rolipram decreased the reinstatement of heroin seeking induced by cues or heroin priming even at the lowest dose (0.03 mg/kg); in contrast, the highest dose (0.3 mg/kg) of rolipram was required to decrease sucrose reinforcement. Finally, the effects of rolipram on heroin-seeking behavior were correlated with the increases in expression of phosphorylated CREB in the nucleus accumbens. The study demonstrated that rolipram inhibited heroin reward and heroin-seeking behavior. The results suggest that PDE4 plays an essential role in mediating heroin seeking and that PDE4 inhibitors may be used as a potential pharmacotherapeutic approach for heroin addiction.

Topics: Animals; Conditioning, Operant; CREB-Binding Protein; Cues; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Extinction, Psychological; Heroin; Heroin Dependence; Male; Narcotics; Phosphodiesterase 4 Inhibitors; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Reward; Rolipram; Self Administration

The cellular mechanisms by which opiate addiction develops with repetitive use remain largely unresolved. Intercellular calcium homeostasis is one of the most critical elements to determine neuroadaptive changes and neuronal fate. Heroin, one of the most addictive opiates, may induce neurotoxicity potentially inducing brain impairment, especially for those chronic users who get an overdose. Here we examined changes in intracellular calcium concentration ([Ca2+]i) after repeated exposure to heroin using cultured cerebral cortical neurons. Dynamic changes in [Ca2+]i indicated by fluo-3-AM were monitored using confocal laser scan microscopy, followed by cytotoxicity assessments. It showed that the cells dissociated from heroin-dependent rats had a smaller depolarization-induced [Ca2+]i responses, and a higher elevation in [Ca2+]i when challenged with a high concentration of heroin (500 μM). The restoration ability to remove calcium after washout of these stimulants was impaired. Calcium channel blocker verapamil inhibited the heroin-induced [Ca2+]i elevations as well as the heroin-induced cell damage. The relative [Ca2+]i of the nerve cells closely correlated with the number of damaged cells induced by heroin. These results demonstrate that nerve cells from heroin-dependent rats manifest abnormal [Ca2+]i homeostasis, as well as vulnerability to heroin overdose, suggesting involvement of [Ca2+]i regulation mechanisms in heroin addiction and neurotoxicity.

Topics: Animals; Calcium; Cells, Cultured; Heroin; Heroin Dependence; Homeostasis; Male; Narcotics; Neurons; Rats; Rats, Sprague-Dawley

Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (

Topics: Analgesics, Opioid; Biomarkers; Buprenorphine; Chromatography, Liquid; Chronic Pain; Codeine; Heroin; Heroin Dependence; Humans; Illicit Drugs; Methadone; Morphine Derivatives; Pain Clinics; Tandem Mass Spectrometry

Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse.

Topics: Animals; Antidepressive Agents, Second-Generation; Depression; Disease Models, Animal; Dorsal Raphe Nucleus; Fluoxetine; Heroin; Heroin Dependence; Male; Memory Disorders; Memory, Short-Term; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Narcotics; Receptors, Opioid, kappa; Receptors, Opioid, mu; Social Behavior; Spatial Memory; Substance Withdrawal Syndrome

New Mexico has consistently high rates of drug-induced deaths, and opioid-related treatment admissions have been increasing over the last two decades. Youth in New Mexico are at particular risk: they report higher rates of nonmedical prescription opioid use than those over age 25, are more likely than their national counterparts to have tried heroin, and represent an increasing proportion of heroin overdoses.. Commissioned by the City of Albuquerque, semistructured interviews were conducted from April to June of 2011 with 24 substance use treatment agencies and eight key stakeholders in Albuquerque to identify recent changes in the treatment-seeking population and gaps in treatment availability. Themes were derived using template analysis and data were analyzed using NVivo 9 software.. Respondents reported a noticeable increase in youth seeking treatment for opioid use and a general increase in nonmedical prescription opioid use. Most noted difficulties with finding buprenorphine providers and a lack of youth services. Additionally, stigma, limited interagency communication and referral, barriers to prescribing buprenorphine, and a lack of funding were noted as preventing opioid users from quickly accessing effective treatment.. Recommendations for addressing these issues include developing youth-specific treatment programs, raising awareness about opioid use among youth, increasing the availability of buprenorphine through provider incentives and education, developing a resource guide for individuals seeking treatment in Albuquerque, and prioritizing interagency communication and referrals.

Topics: Adolescent; Age Factors; Analgesics, Opioid; Buprenorphine; Cause of Death; Cooperative Behavior; Cross-Sectional Studies; Health Planning Councils; Health Services Accessibility; Heroin; Heroin Dependence; Humans; Interdisciplinary Communication; Needs Assessment; New Mexico; Opioid-Related Disorders; Prescription Drugs; Referral and Consultation; Substance Withdrawal Syndrome; Young Adult

Drug abuse and addiction are worldwide health problems. However, few studies have used fMRI to investigate the effect of chronic heroin use on brain activation. This is a study along this line.. fMRI positive sites in the brain were recorded during different motor and sensory activities.. Following motor activities, heroin users had more sites globally activated in the brain than in normal volunteers, with ex-heroin users being least reactive. Conversely, a "heroin puffing" movie produced more activation in ongoing-heroin and ex-heroin users than in the normal individuals, whereas a movie with explicit sexual content was less stimulatory in both groups of heroin users compared to normal individuals.. These significant findings relative to the function of specific brain nuclei are discussed.

Topics: Adult; Arousal; Attention; Brain Mapping; Cerebellum; Cerebral Cortex; Corpus Callosum; Cues; Evoked Potentials; Female; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Motion Pictures; Motor Activity; Proprioception; Reference Values

Three haptens have been synthesized with linkers for attachment to carrier macromolecules at either the piperidino-nitrogen or via an introduced 3-amino group. Two of the haptens, with a 2-oxopropyl functionality at either C6, or at both the C3 and C6 positions on the 4,5-epoxymorphinan framework, as well as the third hapten (DiAmHap) with diamido moieties at both the C3 and C6 positions, should be much more stable in solution, or in vivo in a vaccine, than a hapten with an ester in one of those positions, as found in many heroin-based haptens. A "classical" opioid synthetic scheme enabled the formation of a 3-amino-4,5-epoxymorphinan which could not be obtained using palladium chemistry. Our vaccines are aimed at the reduction of the abuse of heroin and, as well, at the reduction of the effects of its predominant metabolites, 6-acetylmorphine and morphine. One of the haptens, DiAmHap, has given interesting results in a heroin vaccine and is clearly more suited for the purpose than the other two haptens.

Topics: Animals; Female; Haptens; Heroin; Heroin Dependence; Macromolecular Substances; Mice; Mice, Inbred BALB C; Molecular Conformation; Vaccines

Topics: Adult; Anabolic Agents; Androgens; Focus Groups; Heroin; Heroin Dependence; Humans; Male; Substance-Related Disorders; Young Adult

Overdose is a major cause of morbidity and mortality amongst opioid users. This paper reported recent non-fatal overdose amongst the Australian Treatment Outcome Study (ATOS) cohort at 11-year follow-up, and characteristics that predict recent overdose.. Longitudinal cohort, with 431 (70.1%) of the original 615 participants interviewed. Participants were administered the ATOS structured interview, addressing demographics, treatment history, drug use, heroin overdose, criminality, health and psychopathology.. Mean time since heroin initiation was 20.4 years. By 11-year follow-up, the proportion who had overdosed was 67.5%, and 24.4% had experienced five or more overdoses. In the 12 months preceding 11-year follow-up, 4.9% had overdosed (11.8% of those who had used heroin in that period). Of the 21 participants who had recently overdosed, 20 (95.2%) had overdosed previously, and 19 (90.5%) were not enrolled in a treatment programme at the time. Those who had recently overdosed reported higher levels of use of opiates other than heroin (57.1% vs 24.9%), benzodiazepines (61.9% vs 30.5%,), methamphetamine (38.1% vs 16.8%) and cocaine (19.0% vs 3.7%). They also had exhibited higher levels of heroin use and other drug use at baseline, 12 and 24 month follow-ups.. While the prevalence had declined, overdoses still occurred. A history of overdose and polydrug use patterns continued to provide strong markers for those at continued risk.

Topics: Adult; Australia; Cohort Studies; Drug Overdose; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Middle Aged; Time Factors; Treatment Outcome

Topics: Commerce; Drug Overdose; Heroin; Heroin Dependence; Humans

To analyze the electrical activity property changes in nucleus accumbens (NAc) of heroin-induced conditioned place preference (CPP) rats during different stages of heroin dependence and to explore NAc's roles in the formation of drug dependence.. Recording electrodes were bilaterally embedded into the NAcs of rats with the aid of stereotaxic apparatus, followed by establishment of heroin-dependent rat model. The NAc electrical activity during 3 different stages of heroin dependence, including heroin pre-exposure, immediate post-exposure and heroin withdrawal, were respectively recorded using EEG wireless telemetry techniques. The frequency distribution (ranging from 0.5 to 30 Hz) and the amplitude of NAc electrical activity were analyzed and measured.. Heroin-dependent rat models were successfully established and their withdrawal symptoms were evident. All rats showed a conditioned place preference (CPP) for the white box after 5-10 days of heroin-exposure, and displayed a maximum withdrawal symptoms on 2d after heroin- withdrawal. During all statges of heroin-dependence, the NAc electrical activity contained the highest proportion of delta rhythm and the lowest proportion of alpha2 rhythm. The discharge frequence band was similar across different stages. There was a significantly increased ratio of low-frequency discharges (delta rhythm) and decreased ratio of high-frequency discharges (beta rhythm) in NAc of rats during the immediate post- heroin exposure stage when compared with that during pre-exposure and heroin withdrawal stages. During the withdrawal stage, the ratio of at rhythm was significantly lower than during pre- and post-heroin exposure stages (P < 0.01). Further, the mean discharge amplitude in NAcs during immediate post-exposure and withdrawal stages was significantly increased relative to pre-exposure stage. However, the mean discharge amplitude during heroin withdrawal stage was significantly lower than during immediate post-exposure stage.. The electrical activity properties in rat NAcs showed a significant change during different stages of heroin-dependence, which suggested that neuronal activities in NAcs might contribute to the modulation of drug-dependence.

Topics: Animals; Conditioning, Operant; Heroin; Heroin Dependence; Male; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Telemetry

The antimicrobial peptide cathelicidin is critical in killing pathogens by innate immune cells, including Mycobacterium tuberculosis and Candida albicans. These pathogens often cause infections in opioid users, a risk that is greatly increased with concurrent human immunodeficiency virus (HIV) infection. Therefore, we examined the association between opioid use and cathelicidin in HIV-infected subjects from Bandung, Indonesia. The following three groups of HIV-infected individuals were included: (i) Active drug users: used heroin in the last 30 days; (ii) Methadone clients: received methadone maintenance therapy in the last 30 days; and (iii). never used opioids or did not use opioids in the year preceding inclusion. In addition to interviews, blood samples were taken to examine the RNA expression of cathelicidin. We found that the RNA expression of cathelicidin was significantly decreased (p=0.007) in heroin users, compared with controls. Opioids are associated with immunosuppression, and cathelicidin could be an important factor in this association. However, more research is needed to examine the direct effects of decreased cathelicidin levels.

Topics: Adult; Antimicrobial Cationic Peptides; Blood Cells; Cathelicidins; Female; Heroin; Heroin Dependence; HIV Infections; Humans; Immunosuppressive Agents; Indonesia; Interviews as Topic; Male; RNA, Messenger; Young Adult

Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats.. Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks. The selective mGluR5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 5, 15 and 50 nmol per side) was then microinjected into the NAc core or shell 10 min before a heroin-seeking test induced by context, cues or heroin priming.. Microinjection of MPEP into the NAc shell dose-dependently decreased the heroin seeking induced by context, cues or heroin priming. In contrast, microinjection of MPEP into the NAc core did not alter the heroin seeking induced by cues or heroin priming. In addition, microinjection with MPEP (15 nmol per side) in the NAc shell reversed both the percentage of open arms entries (OE%) and the percentage of time spent in open arms (OT%) after heroin withdrawal. Microinjection of MPEP (50 nmol per side) in the striatum as a control location did not affect the heroin seeking behavior. Microinjection of MPEP in the 3 locations did not change the locomotion activities.. Blockade of mGluR5 in NAc shell in rats specifically suppresses the relapse to heroin-seeking and anxiety-like behavior, suggesting that mGluR5 antagonists may be a potential candidate for the therapy of heroin addiction.

Topics: Analgesics, Opioid; Animals; Anxiety; Behavior, Animal; Cues; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Excitatory Amino Acid Antagonists; Heroin; Heroin Dependence; Locomotion; Male; Nucleus Accumbens; Pyridines; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5; Recurrence; Self Administration; Substance Withdrawal Syndrome; Time Factors

A 49-year-old man presented to the emergency department (ED) with shoulder pain after intramuscular injection of heroin into his right deltoid muscle. Point-of-care (POC) ultrasound identified a subdeltoid abscess, and ultrasound-guided aspiration of the fluid collection was performed. The patient was admitted and improved on antibiotics and made a complete recovery. POC ultrasound and ultrasound-guided aspiration can assist in the diagnosis and treatment of deep musculoskeletal abscesses.

Topics: Abscess; Biopsy, Fine-Needle; Deltoid Muscle; Drainage; Heroin; Heroin Dependence; Humans; Injections, Intramuscular; Male; Middle Aged; Point-of-Care Systems; Shoulder Pain; Substance Abuse, Intravenous; Ultrasonography, Interventional

The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Disease Management; Female; Heroin; Heroin Dependence; Humans; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Substance Withdrawal Syndrome; Young Adult

The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate. Vaccination with M-KLH blocked heroin-primed reinstatement of heroin responding. Vaccination also decreased HSA at low heroin unit doses but produced a compensatory increase in heroin self-administration at high unit doses. Vaccination shifted the heroin dose-response curve to the right, indicating reduced heroin potency, and behavioral economic demand curve analysis further confirmed this effect. In a separate experiment heroin was administered at rates simulating heroin exposure during HSA. Heroin and its active metabolites, 6-acetylmorphine (6-AM) and morphine, were retained in plasma and metabolite concentrations were reduced in brain in vaccinated rats compared to controls. Reductions in 6-AM concentrations in brain after vaccination were consistent with the changes in HSA rates accompanying vaccination. These data provide evidence that 6-AM is the principal mediator of heroin reinforcement, and the principal target of the M-KLH vaccine, in this model. While heroin vaccines may have potential as therapies for heroin addiction, high antibody to drug ratios appear to be important for obtaining maximal efficacy.

Topics: Animals; Brain; Heroin; Heroin Dependence; Male; Morphine; Morphine Derivatives; Rats; Self Administration; Vaccines, Conjugate

To investigate the impact of heroin for antiviral treatment, drug resistance, mutation types and frequency in HIV/AIDS patients in Guangxi Zhuang Autonomous Region.. HIV/AIDS patients were recruited in Methadone Maintenance Treatment Clinics, HIV/AIDS Clinic and HIV Voluntary Counseling and Testing Center Liuzhou and Baise city from April 2008 to October 2009. The patients were grouped by the situation of antiviral treatment and use of heroin. A total of 435 HIV/AIDS patients were recruited, among which 108 cases in antiviral treatment and heroin group, 93 cases in antiviral treatment and never using drug group, 105 cases in no antiviral treatment and using heroin group, 129 cases in no antiviral treatment and never using drug group. The effect of antiviral treatment was evaluated by questionnaire survey, viral load measurement and CD4(+) T lymphocyte count. HIV-1 RNA from plasma was extracted, and then the pol genes were amplified and sequenced. The sequences were analyzed for HIV-1 genotype drug-resistance.. For the patients who received antiviral treatment, the viral load in heroin group was higher than that in never using drug group (lg (2.61 ± 1.24) vs lg (2.08 ± 0.80), t = 3.54, P < 0.05) , and the percentage of viral load lower than 1 000 copies/ml in heroin group was significantly less than that in never using drug group (63.9% vs 86.0%,χ(2) = 12.76, P < 0.05). For the patients who received antiviral treatment, the difference has no significance in CD4(+) T lymphocyte count between heroin group and never using drug group ((337.92 ± 181.66) vs (326.14 ± 254.98), t = 0.38, P = 0.703). For the patients who didn't receive antiviral treatment, the difference also has no significance in CD4(+) T lymphocyte count between heroin group and never using drug group ((373.73 ± 155.97) vs (337.53 ± 209.26), t = 1.47, P = 0.143). For the patients who received antiviral treatment, there was no difference in the percentage of the CD4(+) T lymphocyte count more than 350/ml between heroin group and never using drug group (48.1% vs 43.0%, χ(2) = 0.53, P = 0.466). 319 HIV-1 pol gene sequences were obtained. Among the patients who received antiviral treatment, the mutation frequency of M184V/I, T215Y/F, L210W and T69N/S in heroin abuser group were significantly higher than that in never using drug group (14.9% (11/74) vs 4.4% (3/68), 12.2% (9/74) vs 1.5% (1/68), 12.2% (9/74) vs 1.5% (1/68) and 10.8% (8/74) vs 1.5% (1/68) respectively) (P < 0.05).. Using heroin may promote HIV replication, reducing the virological response to antiviral treatment and increasing the frequencies of drug resistance loci among HIV/AIDS patients.Heroin rehabilitation may benefit from the antiviral treatment and obtain better antiviral effect.

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Antiviral Agents; CD4 Lymphocyte Count; China; Drug Resistance; Drug Resistance, Viral; Genes, pol; Heroin; Heroin Dependence; HIV Infections; HIV-1; Humans; Mutation; Mutation Rate; Viral Load

Psychoactive drugs are responsible for pathological changes in the mouth including dental caries, which most troublesome. The aim of the present study was to evaluate the effect of heroin on several salivary factors which are involved in the oral health and their changes after methadone maintenance therapy (MMT).. Forty patients with heroin abuse history, who referred to Imam Reza Hospital for MMT were included. Saliva sampling was carried out two times; at the first visit (time 1) and repeated 1 month after MMT (time 2). The saliva was analyzed immediately to evaluate the total volume, Ph, CPR, the Uric acid concentration, nitric oxide and antioxidant capacity.. The mean values for saliva volume, pH, CRP, Uric acid, antioxidant and nitric oxide were 0.38 ± 0.14, 7.63 ± 1.22, 5.2 ± 2.3, 1.47 ± 0.8, 0.80 ± 0.23, and 0.26 ± 0.03, respectively at first visit and 0.34 ± 0.22, 7.37 ± 1.01, 6.1 ± 2.6, 2.18 ± 0.9, 0.74 ± 0.3 and 0.29 ± 0.08 after 1 month of MMT. These values are below the normal ranges; however, there was no significant difference between two times in term of saliva volume, pH and saliva component (p > 0.05).. Heroin addiction changed the effective salivary factors and therefore could negatively contribute to oral health. These factors were not return to the normal range after 1 month of MMT. Physicians should be informed about focusing on oral health in patients under MMT.

Topics: Adolescent; Adult; Antioxidants; C-Reactive Protein; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Hydrogen-Ion Concentration; Male; Methadone; Middle Aged; Narcotics; Nitric Oxide; Opiate Substitution Treatment; Peroxidase; Saliva; Uric Acid; Young Adult

In rats, reexposure to heroin-paired contexts after extinction of lever responding in a different context reinstates heroin seeking. Previous reports indicate that ventral hippocampus/Ca1 region plays a critical role in cocaine-, cue- and context-induced reinstatement of cocaine seeking. Here, we examined whether ventral subiculum, the output region of ventral hippocampus, is involved in context-induced reinstatement of heroin seeking. We found that reversible inactivation of ventral subiculum, but not posterior Ca1, with the gamma-aminobutyric acid agonists muscimol + baclofen decreased context-induced reinstatement of heroin seeking. Our findings, together with previous studies on cocaine seeking, indicate a critical role of ventral subiculum in context-induced relapse across drug classes.

Topics: Animals; Baclofen; Cues; Drug-Seeking Behavior; Extinction, Psychological; GABA-A Receptor Agonists; Heroin; Heroin Dependence; Hippocampus; Muscimol; Narcotics; Rats; Recurrence; Self Administration

To investigate whether microvascular damage is involved in the pathogenesis of heroin induced spongiform leukoencephalopathy (HSLE).. The brain tissues were collected from 4 HSLE patients and 5 controls and then fixed in 4% paraformaldehyde. The frontal lobe, corpus callosum and cerebellum were separated. The expressions of myelin base protein (MBP) and CD34 were detected by immunohistochemistry. TUNEL staining was applied to detect cell apoptosis. The correlation between microvascular changes and pathological vacuoles was evaluated.. No obvious abnormalities were found in the brain of controls. Immunohistochemistry for MBP showed the collapse and fracture of myelin sheath and vacuole formation in the subcortical white matter, corpus callosum, and cerebellar white matter of HSLE patients. TUNEL staining showed the number of apoptotic cells in the cerebellar white matter and corpus callosum of HSLE patients was significantly higher than that in controls (F = 389.451, P < 0.001). Masson's trichrome staining revealed vacuolar degeneration in the cerebral white matter of HSLE patients, and the vacuoles were distributed around the microvessels. Immunohistochemistry revealed CD34 positive cells were seldom found besides the vessels in the cerebellar white matter and corpus callosum of HSLE patients, but a variety of CD34 positive cells was found in the vascular wall of controls (F = 838.500, P < 0.001).. Apoptosis of oligodendrocytes may be related to the HSLE. Cerebral vascular injury and microcirculation dysfunction are involved in the pathogenesis of HSLE. The interrelation between apoptosis of oligodendrocytes and the microvascular damage are required to be studied in future investigations.

Topics: Adult; Antigens, CD34; Apoptosis; Canavan Disease; Cerebellum; Cerebrovascular Trauma; Corpus Callosum; Female; Frontal Lobe; Heroin; Heroin Dependence; Humans; Male; Microvessels; Middle Aged; Myelin Basic Protein; Oligodendroglia

Drug abuse is associated with epigenetic changes, such as histone modifications and DNA methylation. The purpose of the present study was to examine the effect of chronic cocaine and heroin administration on global DNA methylation in brain and liver. Male, 8 week old, C57BL/6J mice received heroin in a chronic 'intermittent' escalating dose paradigm, or cocaine in a chronic escalating dose 'binge' paradigm, which mimic the human pattern of opioid or cocaine abuse respectively. Following sacrifice, livers and brains were removed and DNA was extracted from them. The extracted DNA was hydrolyzed and 2'-deoxycytidine and 5-methyl-2'-deoxycytidine were determined by HPLC-UV. The % 5-methyl-2'-deoxycytidine content of DNA was significantly higher in the brain compared to the liver. There were no differences between the control animals and the cocaine or heroin treated animals in neither of the tissues examined, which is surprising since cocaine administration induced gross morphological changes in the liver. Moreover, there was no difference in the % 5-methyl-2'-deoxycytidine content of DNA between the cocaine and the heroin treated animals. The global DNA methylation status in the brain and liver of mice chronically treated with cocaine or heroin remains unaffected, but this finding cannot exclude the existence of anatomical region or gene-specific methylation differences. This is the first time that global DNA methylation in the liver and whole brain has been studied following chronic cocaine or heroin treatment.

Topics: Animals; Biomarkers; Brain; Chromatography, High Pressure Liquid; Cocaine; Cocaine-Related Disorders; Deoxycytidine; Disease Models, Animal; DNA Methylation; Heroin; Heroin Dependence; Liver; Male; Mice; Mice, Inbred C57BL; Spectrophotometry, Ultraviolet; Time Factors

We estimate trends and geographical differences in the heroin epidemic in the European Union plus Croatia and Turkey by analyzing aggregated data on first heroin treatment admissions (cases) during 2000-2009. In 2005-2009 the proportion of drug injectors was higher in Central and Eastern European countries (CEECs) than in Western European countries (WECs), whereas the opposite occurred with mean age at first heroin use and first treatment. During this period, the number of cases, cases per center, and proportion of injectors in WECs declined, whereas mean age at first treatment and first heroin use increased. The opposite occurred in Turkey, except for proportion of injectors, while trends were less clear in the other CEECs. In the 7 WECs with data, trends in 2000-2005 and 2005-2009 were similar. This suggests that the number of recent-onset heroin users and heroin injectors may have declined some years before the study period, especially in WECs.

Topics: Adult; Age Factors; Europe; Heroin; Heroin Dependence; Humans; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Time Factors; Young Adult

Although many complications of intravenous drug abuse are well described, "cotton fever" has had little mention in recent medical literature. Cotton fever is street terminology for the post-injection fever experienced by many drug users after "shooting up" with heroin reclaimed from a previously used cotton filter.. We report on a 22-year-old man with a history of intravenous drug abuse with fever 30 min after injecting heroin. He was intensely diaphoretic, tachycardic, and febrile. His workup was negative for any infectious etiology and he later admitted to reusing the same cotton balls for heroin filtration several times over in order to preserve more of the drug.. Although it is usually a benign situation, cotton fever can have a dramatic clinical and hematologic course. We present a typical case of cotton fever followed by a description of the pathophysiology and clinical presentation of this entity.

Topics: Cotton Fiber; Diagnosis, Differential; Equipment Reuse; Fever; Filtration; Heroin; Heroin Dependence; Humans; Male; Narcotics; Sepsis; Substance Abuse, Intravenous; Tachycardia; Young Adult

To assess heroin injectors' perceptions of and responses to a warning issued by public health officials regarding high-potency heroin and increases in fatal overdoses.. Semi-structured qualitative interviews.. Vancouver, Canada.. Eighteen active heroin injectors.. Semi-structured interview guide focussing on heroin injectors' perceptions of and responses to the overdose warning, including reasons for failing to adhere to risk reduction recommendations.. Although nearly all participants were aware of the warning, their recollections of the message and the timing of its release were obscured by on-going social interactions within the drug scene focussed on heroin quality. Many injection drug users reported seeking the high potency heroin and nearly all reported no change in overdose risk behaviours. Responses to the warning were shaped by various social, economic and structural forces that interacted with individual behaviour and undermined efforts to promote behavioural change, including sales tactics employed by dealers, poverty, the high cost and shifting quality of available heroin, and risks associated with income-generating activities. Individual-level factors, including emotional suffering, withdrawal, entrenched injecting routines, perceived invincibility and the desire for intense intoxication also undermined risk reduction messages.. Among heroin injectors in British Columbia, a 2011 overdose warning campaign appeared to be of limited effectiveness and also produced unintended negative consequences that exacerbated overdose risk.

Topics: Adult; British Columbia; Drug Overdose; Drug Users; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Public Health Practice; Qualitative Research; Risk Factors; Substance Abuse, Intravenous

This article highlights the experiences of a unique group. In January 2011, Dave Murray organized a group of participants from the North American Opiate Medication Initiative (NAOMI) heroin-assisted treatment clinical trials from 2005 to 2008 in the Downtown Eastside of Vancouver (DTES), B.C., Canada. The NAOMI Patients Association (NPA) is an independent group that currently meets every Saturday in the DTES. Currently, all members of the NPA are former participants in the heroin stream of the clinical trial. The NPA offers support, education, and advocacy to its members.. Drawing on brainstorming sessions and focus groups that were conducted in the summer of 2011, this paper highlights the experiences of NPA members in their own words.. The findings provide a lens to understand how becoming a research subject for the NAOMI trial impacted the lives of NPA members, both positive and negative. The NPA members discuss ethics, consent, recommendations for future HAT programs and studies, and ongoing advocacy.

Topics: Attitude to Health; Biomedical Research; British Columbia; Clinical Trials as Topic; Cost of Illness; Crime; Ethics, Research; Female; Health Policy; Heroin; Heroin Dependence; Humans; Legislation, Drug; Male; Narcotics; Prescription Drugs; Self-Help Groups; Survivors

Most animal research on drug relapse involves the reinstatement model where abstinence is a result of drug removal (extinction). However, abstinence in humans often results from the aversive consequences that accompany drug seeking (conflict situation). This study was aimed at using a conflict-based animal model of abstinence/relapse in rats self-administering heroin or cocaine.. Rats were trained to self-administer heroin (0.05 mg kg(-1) injection(-1)) or cocaine (0.5 mg kg(-1) injection(-1)) with each injection paired with a light cue. After stable responding was demonstrated, the floor near the levers was electrified, creating a barrier, in order to model the negative consequences of continued drug seeking. Shock intensities were increased over sessions until no responses occurred for three consecutive sessions. During a relapse test, where shock was maintained,the capacity of noncontingent drug cue presentations to induce active lever pressing was assessed.. Ten of ten heroin animals and three of eight cocaine animals exposed to noncontingent cue presentations resumed responding. During the relapse test, for both drug groups, active lever pressing was significantly higher than during abstinence but only in the heroin group was it significantly higher than inactive lever pressing.. The implementation of negative consequences for drug seeking can result in its cessation just as they might in human addicts. Similarly, exposure to drug cues can lead to resumption of drug seeking. This model may be useful for studying the mechanisms underlying abstinence and relapse and for developing strategies to prevent relapse.

Topics: Animals; Cocaine; Cocaine-Related Disorders; Conflict, Psychological; Cues; Disease Models, Animal; Electroshock; Extinction, Psychological; Heroin; Heroin Dependence; Male; Rats; Rats, Long-Evans; Recurrence; Self Administration

Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin's rapid metabolism to 6-acetylmorphine and morphine. We recently developed a "dynamic" vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin's metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin's psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance.

Topics: Animals; Antibodies; Chromatography, Liquid; Heroin; Heroin Dependence; Male; Morphine; Morphine Derivatives; Motivation; Rats; Rats, Wistar; Secondary Prevention; Self Administration; Tandem Mass Spectrometry; Vaccines

To investigate the WM microstructure deficits in heroin dependent individuals (HDIs) with different length of heroin dependence, and to investigate whether these WM deficits can be related to the duration of heroin use and to decision-making deficits in HDIs.. Thirty-six HDIs [including eighteen sHDIs (duration of heroin dependent is less than 10 years) and eighteen lHDIs (duration of dependent is between 10:20 years)] and sixteen healthy controls participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) were performed by tract-based spatial statistics (TBSS) to localize abnormal WM regions among groups. TBSS demonstrated that sHDIs had significantly lower FA than controls in right orbito-frontal WM, bilateral temporal WM and right parietal WM. The lHDIs had significantly lower FA throughout the brain compared with the controls and sHDIs. The lHDIs had significantly lower Da than controls in bilateral inferior frontaloccipital fasciculus, bilateral splenium of corpus callosum, left inferior longitudinal fasciculus, and had significantly higher Dr than controls in bilateral uncinatus fasciculus, bilateral inferior frontaloccipital fasciculus and bilateral cortical spinal fasciculus. Volume-of-interest (VOI) analyses detect the changes of diffusivity indices in the regions with FA abnormalities revealed by control vs sHDIs. In most VOIs, FA reductions were caused by the increase in Dr as well as the decrease in Da. Correlation analysis was used to assess the relationship between FA and behavioral measures in HDIs and controls available. Significantly positively correlations were found between the FA values in the right orbital-frontal WM, right parietal WM and IGT performance.. The extent and severity of WM integrity deficits in HDIs was associated with the length of heroin dependent. Furthermore, abnormal WM microstructure may correlate with decision-making impairments in HDIs.

Topics: Adult; Anisotropy; Case-Control Studies; Cerebral Cortex; Data Interpretation, Statistical; Diffusion Tensor Imaging; Games, Experimental; Heroin; Heroin Dependence; Humans; Male; Narcotics; Neuroimaging; Neuropsychological Tests

Topics: Drug Overdose; Drug Users; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Substance Abuse, Intravenous

The aim of this study was to compare the long-term outcomes of treatment-resistant bipolar 1 heroin addicts with peers who were without DSM-IV axis I psychiatric comorbidity (dual diagnosis).. 104 Heroin-dependent patients (TRHD), who also met criteria for treatment resistance - 41 of them with DSM-IV-R criteria for Bipolar 1 Disorder (BIP1-TRHD) and 63 without DSM-IV-R axis I psychiatric comorbidity (NDD-TRHD) - were monitored prospectively (3 years on average, min. 0.5, max. 8) along a Methadone Maintenance Treatment Programme (MMTP).. The rates for survival-in-treatment were 44% for NDD-TRHD patients and 58% for BIP1-TRHD patients (p=0.062). After 3 years of treatment such rates tended to become progressively more stable. BIP1-TRHD patients showed better outcome results than NDD-TRHD patients regarding CGI severity (p<0.001) and DSM-IV GAF (p<0.001). No differences were found regarding urinalyses for morphine between groups during the observational period. Bipolar 1 patients needed a higher methadone dosage in the stabilization phase, but this difference was not statistically significant.. The observational nature of the protocol, the impossibility of evaluating a follow-up in the case of the patients who dropped out, and the multiple interference caused by interindividual variability, the clinical setting and the temporary use of adjunctive medications.. Contrary to expectations, treatment-resistant patients with bipolar 1 disorder psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.

Topics: Adult; Bipolar Disorder; Diagnosis, Dual (Psychiatry); Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Narcotics; Opiate Substitution Treatment; Prospective Studies; Treatment Outcome; Young Adult

Both compulsory detoxification treatment and community-based methadone maintenance treatment (MMT) exist for heroin addicts in China. We aim to examine the effectiveness of three intervention models for referring heroin addicts released from compulsory detoxification centers to community methadone maintenance treatment (MMT) clinics in Dehong prefecture, Yunnan province, China.. Using a quasi-experimental study design, three different referral models were assigned to four detoxification centers. Heroin addicts were enrolled based on their fulfillment to eligibility criteria and provision of informed consent. Two months prior to their release, information on demographic characteristics, history of heroin use, and prior participation in intervention programs was collected via a survey, and blood samples were obtained for HIV testing. All subjects were followed for six months after release from detoxification centers. Multi-level logistic regression analysis was used to examine factors predicting successful referrals to MMT clinics.. Of the 226 participants who were released and followed, 9.7% were successfully referred to MMT(16.2% of HIV-positive participants and 7.0% of HIV-negative participants). A higher proportion of successful referrals was observed among participants who received both referral cards and MMT treatment while still in detoxification centers (25.8%) as compared to those who received both referral cards and police-assisted MMT enrollment (5.4%) and those who received referral cards only (0%). Furthermore, those who received referral cards and MMT treatment while still in detoxification had increased odds of successful referral to an MMT clinic (adjusted OR = 1.2, CI = 1.1-1.3). Having participated in an MMT program prior to detention (OR = 1.5, CI = 1.3-1.6) was the only baseline covariate associated with increased odds of successful referral.. Findings suggest that providing MMT within detoxification centers promotes successful referral of heroin addicts to community-based MMT upon their release.

Topics: Adolescent; Adult; China; Community Health Services; Female; Heroin; Heroin Dependence; HIV Seropositivity; Humans; Logistic Models; Male; Mandatory Programs; Methadone; Middle Aged; Opiate Substitution Treatment; Police; Referral and Consultation; Young Adult

To reduce heroin availability, the United Nations (UN) has encouraged nations to control acetic anhydride, an essential ("precursor") chemical typically necessary to the drug's production. This effort, a major environmental prevention policy, has received little evaluation. The United States, per the UN's lead, implemented acetic anhydride regulation in 11/1989. The present study examines whether the US regulation impacted US heroin availability.. Monthly series of three heroin availability indicators-heroin purity, heroin price, and amount of heroin seized-were constructed for the conterminous United States, the US Southwest (supplied predominantly with Mexican-produced heroin), and the US Northeast (supplied predominantly, at the time, with Southeast Asian-produced heroin). Data came from the System to Retrieve Information from Drug Evidence (01/1987-04/2011). Impacts were assessed using ARIMA-intervention time series analysis.. In each US area, heroin purity and amount seized rose and price decreased throughout the pre-intervention period. All of the indicators then reversed course at the time of the regulation. In the conterminous United States, the US Northeast, and the US Southwest, purity decreased (-40%, -25% and -50%, respectively); amount seized decreased (-27%, -37% and -39%, respectively); and price rose (+93%, +102% and +296%, respectively). Impacts lasted 2-5 years.. US heroin availability decreased in association with the US acetic anhydride regulation. The impacts in the US Southwest and US Northeast suggest that heroin production in Mexico and Southeast Asia, respectively, was constrained. This study lends support to the contention that essential ("precursor") chemical control can be used to help address heroin.

Topics: Acetic Anhydrides; Algorithms; Databases, Factual; Heroin; Heroin Dependence; Legislation, Drug; Narcotics; New England; Southwestern United States; United States

Heroin is among the most widely used and dangerous addictive opiate. The World Health Organization (WHO) estimated that more than 15 million people are under the influence of opiate addiction. The aim of this study was to investigate copper zinc-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and selenium-dependent glutathione peroxidase (Se-GPx) antioxidant enzyme activities, malondialdehyde (MDA) levels and the frequency of micronuclei (MN) in addicts using heroin, the most commonly abused opiate in Turkey. Addicts were defined as individuals diagnosed according to "Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)" criteria by the "Alcohol and Substance Abuse Treatment and Education Centre-Ankara (AMATEM)". The control group had no addiction. In comparisons between the groups, a significant decrease in Cu,Zn-SOD activity and increases in MDA levels and MN frequency were observed in addicts. It can be concluded that opiates may cause oxidative stress and that antioxidant supplementation, in addition to pharmacological and psychiatric approaches, can reduce the toxicological effects of these opiates.

Topics: Adolescent; Adult; Catalase; Erythrocytes; Glutathione Peroxidase; Heroin; Heroin Dependence; Humans; Male; Malondialdehyde; Micronuclei, Chromosome-Defective; Micronucleus Tests; Middle Aged; Oxidative Stress; Superoxide Dismutase; Turkey; Young Adult

Topics: Canada; Drug Prescriptions; Government Programs; Heroin; Heroin Dependence; Humans; Narcotics

The link between nasal inhalation of cocaine and nasal and palatal necrosis is well documented. In contrast, few data are available concerning nasal mucosa necrosis related to heroin snorting. The authors report here the retrospective analysis of 24 cases of orofacial lesions in patients with nasal heroin usage, collected between 2006 and 2012.. The cases concern 17 males and 7 females (median age 29.5 (range: 24-42)) with chronic consumption of intranasal heroin (from 2 months to more than 10 years). Six patients had a history of cocaine abuse. The median daily amount of heroin consumption was 5 g (range: 0.5-10). The complications were nasal perforation (11 cases), nasal ulceration or erythema (5 cases), nasal septum necrosis (5 cases), pharyngeal ulceration (3 cases), and palate damages (5 cases). The most common clinical signs and symptoms were nasal pain, purulent sputum, dysphagia, and rhinitis. Maintenance therapy with methadone (19 cases) or buprenorphine (3 cases) was initiated. In 8 cases, the injury improved.. The potential of heroin to induce destructive orofacial lesions should be considered when nasal damages are observed in patients with drug abuse. A multidisciplinary approach seems to be the most effective means of managing such patients.

Topics: Administration, Intranasal; Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Necrosis; Nose; Opiate Substitution Treatment; Palate, Soft; Pharynx

Implementation of injectable heroin treatment for patients with chronic heroin dependence unresponsive to oral methadone maintenance treatment has stagnated, even though the evidence for its effectiveness in this population continues to accrue. This is due to a range of political and environmental factors, not least of which is the cost of the treatment. The article by Byford et al in this issue of the Journal goes some way to increasing the evidence base for the cost-effectiveness of injectable heroin treatment compared with other treatment options. Questions still remain though about the funding implications for government departments, commissioners and providers, given that the sector that is responsible for the majority of the cost, healthcare, is not the same sector that sees the majority of the cost savings, criminal justice.

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Outcome Assessment, Health Care

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake. The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats. Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e. lever presses do not result in heroin delivery). The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.

Topics: Animals; Behavior, Addictive; Conditioning, Operant; Female; Food Deprivation; Heroin; Heroin Dependence; Male; Rats; Self Administration

The article deals with the data of study of biochemical indicators and activity of particular proteolytic enzymes in blood serum of patients with heroin drug addiction. The results can be applied to detect the typical laboratory changes intrinsic to this kind of intoxication.

Topics: Adolescent; Adult; Female; Heroin; Heroin Dependence; Humans; Male; Peptide Hydrolases

Topics: Attitude of Health Personnel; Drug Prescriptions; Heroin; Heroin Dependence; Hospitalization; Hospitals, University; Humans; Nurse-Patient Relations; Nursing Staff, Hospital; Substance Abuse, Intravenous; Switzerland

Brain distribution pattern of "street" heroin metabolites (morphine and codeine) was investigated in two fatalities due to "acute narcotism". A suitable sample pretreatment prior to solid-phase-extraction was developed to achieve a good recovery of the analytes and to eliminate the interfering species. After derivatization with MSTFA, samples were analyzed by GC/MS. Specificity, accuracy, precision and linearity of the method were evaluated; LOD and LOQ were, respectively, 10ng/25ng for morphine and 5ng/10ng for codeine. This method was applied to the analysis of six brain areas (hippocampus, frontal lobe, occipital lobe, nuclei, bulb and pons) coming from two cases of heroin-related deaths. No evidence of accumulation of metabolites in a specific brain region was found.

Topics: Adult; Brain; Codeine; Drug Overdose; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Illicit Drugs; Limit of Detection; Male; Molecular Structure; Morphine; Reproducibility of Results; Substance Abuse Detection; Tissue Distribution

In this paper, we explore the understudied phenomenon of "low-frequency" heroin injection in a sample of street-recruited heroin injectors not in drug treatment. We conducted a cross-sectional study of 2,410 active injection drug users (IDUs) recruited in San Francisco, California from 2000 to 2005. We compare the sociodemographic characteristics and injection risk behaviors of low-frequency heroin injectors (low-FHI; one to 10 self-reported heroin injections in the past 30 days) to high-frequency heroin injectors (high-FHI; 30 or more self-reported heroin injections in the past 30 days). Fifteen percent of the sample met criteria for low-FHI. African American race, men who have sex with men (MSM) behavior, and injection and noninjection methamphetamine use were independently associated with low-FHI. Compared to high-FHI, low-FHI were less likely to report syringe sharing and nonfatal heroin overdose. A small but significant proportion of heroin injectors inject heroin 10 or less times per month. Additional research is needed to qualitatively examine low-frequency heroin injection and its relationship to drug use trajectories.

Topics: Adolescent; Adult; Confidence Intervals; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Needle Sharing; Odds Ratio; San Francisco; Substance Abuse, Intravenous; Surveys and Questionnaires; Young Adult

Heroin addiction is characterized by recurrent cycles of drug use, abstinence, and relapse. It is likely that neurobiological changes during chronic heroin exposure persist across withdrawal and impact behavioral responses to re-exposure. We hypothesized that, after extended withdrawal, heroin-withdrawn rats would express behavioral tolerance and/or sensitization in response to heroin re-exposure and that these responses might be associated with altered mu-opioid receptor (MOPr) activity.. Male Fischer rats were exposed chronically to escalating doses of heroin (7.5-75 mg/kg/day), experienced acute spontaneous withdrawal and extended (10-day) abstinence, and were re-exposed chronically to heroin. Homecage behaviors and locomotor activity in response to heroin, as well as somatic withdrawal signs, were recorded. Separate groups of rats were sacrificed after extended abstinence and MOPr expression and G-protein coupling were analyzed using [(3)H]DAMGO and [(35)S]GTPγS assays.. The depth of behavioral stupor was lower during the initial days of heroin re-exposure compared to the initial days of the first exposure period. Behavioral responses (e.g., stereotypy) and locomotion were elevated in response to heroin re-exposure at low doses. Rats conditioned for heroin place preference during the chronic re-exposure period expressed heroin preference during acute withdrawal; this preference was stronger than rats conditioned during chronic heroin exposure that followed chronic saline and injection-free periods. Extended withdrawal was associated with increased MOPr expression in the caudate-putamen and frontal and cingulate cortices. No changes in G-protein coupling were identified.. Aspects of tolerance/sensitization to heroin are present even after extended abstinence and may be associated with altered MOPr density.

Topics: Animals; Behavior, Addictive; Behavior, Animal; Dose-Response Relationship, Drug; Drug Tolerance; Heroin; Heroin Dependence; Male; Motor Activity; Rats; Rats, Inbred F344; Receptors, Opioid, mu; Substance Withdrawal Syndrome

Metabolomics allows the high-throughput analysis of low molecular mass compounds in biofluids, which can reflect the metabolic response of the body to heroin exposure and potentially reveal biomarkers of heroin abuse.. Heroin was administered to Sprague-Dawley rats in increasing doses from 3 to 16.5 mg kg(-1)d(-1) (i.p.) for 10 days, then withdrawn and re-administered for 4 days. The analytes in serum and urine were profiled using gas chromatography-mass spectrometry, and metabolic patterns were evaluated based on the metabolomics data.. Both the administration and withdrawal of heroin resulted in aberrant behaviour in the rats; however, the rats gradually became adapted to heroin. Metabolomics data showed that heroin administration caused deviations in the metabolic patterns, whereas heroin withdrawal restored the metabolic patterns towards baseline. Re-administration of heroin caused the metabolic patterns to deviate again. Analysis of the metabolites revealed that heroin induced an acceleration of the tricarboxylic acid cycle and the metabolism of free fatty acids that may contribute to the reduction in observed body weight in the heroin group. Heroin administration decreased tryptophan and 5-hydroxytryptamine levels in peripheral serum but increased urinary tryptophan and 5-hydroxyindoleacetate. Withdrawal of heroin for 4 days efficiently restored all metabolites to baseline, except serum myo-inositol-1-phosphate, threonate, and hydroxyproline in the urine.. Heroin administration significantly perturbed metabolic pathways, elevated energy metabolism, whereas heroin withdrawal restored all but a few metabolites to baseline. These peripheral metabolites were indicated as the surrogates characterising the metabolic effect of heroin on central nervous system function.

Topics: Animals; Biomarkers; Energy Metabolism; Heroin; Heroin Dependence; Injections, Intraperitoneal; Male; Metabolomics; Phenotype; Random Allocation; Rats; Rats, Sprague-Dawley

Previous research with an animal model of relapse has shown that acute food deprivation will reinstate extinguished drug seeking. Recent evidence with humans, however, suggests that chronic food restriction rather than acute food deprivation is related to increases in drug taking and relapse, emphasizing a need for an animal model to elucidate the neural mechanisms mediating the effects of chronic food restriction on drug seeking. Here we studied the effects of chronic food restriction during a period of abstinence on heroin seeking in rats.. Rats were trained to self-administer heroin over 10 days (0.1 mg/kg/infusion; i.v.). Rats were then removed from the operant conditioning chambers and exposed to a mild food restriction (resulting in 10-15 % decrease in body weight) or given unrestricted access to food for 14 days while abstinent. The abstinence period was followed by a drug-seeking test under extinction conditions. Subsequent experiments manipulated the length of restriction and test conditions.. Rats that were food restricted throughout the abstinence period demonstrated a robust increase in cue-induced heroin seeking compared to sated rats. Re-feeding prior to testing or decreasing the length of the food restriction period prevented the augmentation of drug seeking.. A combination of chronic food restriction and a concurrent state of hunger appears to be necessary for an increase in cue-induced heroin seeking following abstinence. The procedure presented here may serve as a useful model to study the increased risk for relapse following dietary manipulations in abstinent subjects.

Topics: Animals; Behavior, Addictive; Conditioning, Operant; Cues; Disease Models, Animal; Eating; Food Deprivation; Heroin; Heroin Dependence; Hunger; Male; Rats; Rats, Long-Evans; Recurrence; Self Administration; Time Factors

Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely correlates of sensitivity to behavioral reinforcement in rats: physical withdrawal and locomotor sensitization.. Adolescent (35 days old at start) and adult (79 days old) male Sprague-Dawley rats were administered escalating doses of heroin, increasing from 1.0 to 8.0 mg/kg (i.p.) every 12 h, across 13 days. Somatic signs of spontaneous withdrawal were scored 12 and 24 h after the last injection, and then every 24 h for 5 days; locomotion was recorded concurrently. Challenge injections of heroin (1 mg/kg i.p.) were given at four points: as the first of the escalating doses (day 1), at days 7 and 13 during the escalating regimen, and after 12 days of forced abstinence. Body mass and food intake were measured throughout experimentation.. A heroin withdrawal syndrome was not observed among adolescents as it was among adults, including somatic signs as well as reduced locomotion, body mass, and food intake. On the other hand, heroin-induced locomotor sensitization did not differ across ages.. Reduced withdrawal is consistent with the attenuated reinforcing effects of heroin among adolescent male rats that we reported previously. Thus, it is possible that adolescent rats could reveal important neuroprotective factors for use in treatment of heroin dependence.

Topics: Aging; Animals; Body Weight; Dose-Response Relationship, Drug; Eating; Heroin; Heroin Dependence; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome

Surgical ablation of select brain areas has been frequently used to alleviate psychological dependence on opiate drugs in certain countries. However, ablative brain surgery was stopped in China in 2004 due to the related ethical controversy and possible side effects. Deep brain stimulation (DBS), a less invasive, reversible and adjustable process of neuromodulation, was adopted to attenuate relapses in studies of drug addiction.. Preclinical experiments were designed to assess the long-term effects of DBS of the nucleus accumbens (NAc) on cue- and heroin-induced reinstatement of drug seeking behaviors. After a rat self-administration model of heroin relapse was established, DBS was administered bilaterally or unilaterally to the NAc core through concentric bipolar electrodes. A 1-h long continuous stimulation (130 Hz, 100 μs, 0-150 μA) was given daily for 7 days during the abstinence session. Drug seeking behaviors were elicited by conditioned cues or a small dose of heroin.. 75 μA and 150 μA bilateral NAc DBS attenuated cue- and heroin-induced reinstatement of drug seeking, and unilateral DBS of the right NAc achieved effects almost equivalent to bilateral DBS. Additional experiments showed that DBS had no long-term influence on locomotor activity and spatial learning and retention capabilities in Morris water maze tasks. Subsequent immunohistochemistry measurements revealed that the behavioral consequences were associated with a significant increase in the expression of pCREB and a reduction in the expression of ΔFosB in the NAc.. These findings indicate that the NAc DBS could be an effective and safe therapeutic option for preventing relapse to heroin addiction.

Topics: Animals; Catheterization; Conditioning, Operant; Cues; Cyclic AMP Response Element-Binding Protein; Deep Brain Stimulation; Drug-Seeking Behavior; Electrodes, Implanted; Heroin; Heroin Dependence; Immunohistochemistry; Injections, Intraperitoneal; Male; Maze Learning; Motor Activity; Narcotics; Nucleus Accumbens; Phosphorylation; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Self Administration

The aim of this study was to investigate the effects of transitioning from non-injection heroin use to injection drug use on sexual risk behavior. Non-injecting heroin users age 16-30 were enrolled from 2002 to 2005, and were re-interviewed at 6-month intervals for up to three years; 561 participants completed at least one follow-up interview. The majority of participants were non-Hispanic (NH) Black (54 %), 23 % were Hispanic, and 21 % were NH white. During follow-up, 154 participants (27.5 %) transitioned to injecting drugs. Logistic regression analyses were conducted using generalized estimating equations (GEE) to estimate the effect of transition to injection drug use on changes in sexual risk behavior during follow-up. Transition to injection drug use during follow-up was associated with increased likelihood of sexual risk behavior, especially for men. Harm reduction efforts that focus on preventing initiation or return to injection among non-injecting drug users may also ameliorate HIV sexual risk behaviors.

Topics: Adolescent; Adult; Black or African American; Chicago; Cross-Sectional Studies; Drug Substitution; Female; Heroin; Heroin Dependence; Hispanic or Latino; HIV Infections; Humans; Longitudinal Studies; Male; Socioeconomic Factors; Substance Abuse, Intravenous; Unsafe Sex; White People; Young Adult

Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration.

Topics: Age Factors; Animals; Behavior, Addictive; Conditioning, Operant; Heroin; Heroin Dependence; Male; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Self Administration

Opioid overdose is a leading cause of accidental death in the United States.. To estimate the cost-effectiveness of distributing naloxone, an opioid antagonist, to heroin users for use at witnessed overdoses.. Integrated Markov and decision analytic model using deterministic and probabilistic analyses and incorporating recurrent overdoses and a secondary analysis assuming heroin users are a net cost to society.. Published literature calibrated to epidemiologic data.. Hypothetical 21-year-old novice U.S. heroin user and more experienced users with scenario analyses.. Lifetime.. Societal.. Naloxone distribution for lay administration.. Overdose deaths prevented and incremental cost-effectiveness ratio (ICER).. In the probabilistic analysis, 6% of overdose deaths were prevented with naloxone distribution; 1 death was prevented for every 227 naloxone kits distributed (95% CI, 71 to 716). Naloxone distribution increased costs by $53 (CI, $3 to $156) and quality-adjusted life-years by 0.119 (CI, 0.017 to 0.378) for an ICER of $438 (CI, $48 to $1706).. Naloxone distribution was cost-effective in all deterministic and probabilistic sensitivity and scenario analyses, and it was cost-saving if it resulted in fewer overdoses or emergency medical service activations. In a "worst-case scenario" where overdose was rarely witnessed and naloxone was rarely used, minimally effective, and expensive, the ICER was $14 000. If national drug-related expenditures were applied to heroin users, the ICER was $2429.. Limited sources of controlled data resulted in wide CIs.. Naloxone distribution to heroin users is likely to reduce overdose deaths and is cost-effective, even under markedly conservative assumptions.. National Institute of Allergy and Infectious Diseases.

Topics: Adult; Cost-Benefit Analysis; Decision Support Techniques; Drug Overdose; Heroin; Heroin Dependence; Hospital Costs; Humans; Markov Chains; Naloxone; Narcotic Antagonists; United States; Young Adult

To identify the prevalence and correlates of midazolam injection among injecting drug users in Thailand.. Serial cross-sectional mixed-methods study.. Bangkok, Thailand..   A total of 435 adults who had injected drug(s) in the past 6 months were recruited through peer outreach and word of mouth in Bangkok in 2011.. Multivariable logistic regression was used to analyze self-reported data collected through an interviewer-administered survey in July-October 2011 (n = 435). Additionally, qualitative data were collected in June-July 2009 (n = 10) and analyzed to explore the health problems attributable to midazolam injection.. Among 435 survey participants, the prevalence of daily midazolam injection in the past 6 months was 37.0% (95% confidence interval: 32-42). While 75.8% of the daily midazolam injectors identified heroin as their drug of choice, 91.8% of these individuals reported substituting heroin with midazolam when heroin was unavailable. In multivariable analyses, daily midazolam injection was associated with femoral vein injection [adjusted odds ratio (AOR) = 4.48], polydrug use (AOR = 4.94), daily heroin injection (AOR = 3.25), binge use (AOR = 1.75) and perceived increase in policing pressure (AOR = 1.95) (all P < 0.05). Qualitative accounts indicated severe health problems associated with midazolam injection, including nerve and vascular injuries.. Midazolam misuse is increasing among injecting drug users in Bangkok and appears to be used primarily as a substitute for heroin. Midazolam injection was associated independently with various risk factors for injection-related complications. Given the many deleterious effects of midazolam injection, novel interventions for midazolam injectors are needed urgently.

Topics: Adult; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Hypnotics and Sedatives; Male; Midazolam; Middle Aged; Narcotics; Prevalence; Risk Factors; Self Report; Substance Abuse, Intravenous; Thailand

Heroin is a highly addictive drug, and heroin abuse is considered to be a serious criminal act. The major metabolite of heroin, morphine, can usually be detected as evidence of heroin abuse. However, it is difficult to determine heroin use when morphine and codeine are both detected, because codeine use will also result in the presence of morphine in urine. Therefore, it is important to distinguish heroin abuse from codeine administration. In this study, urine samples from 21 volunteers with various ingestion patterns of a compound codeine phosphate oral solution were used as negative controls, and urine samples from 89 alleged heroin users were used as positive controls. Urine from single and multiple doses of codeine administration were collected at different time points for a systematic comparison. After protein precipitation, the urine samples were analyzed for the presence of free morphine, free codeine and their metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The method of percentiles, with median and standard interquartile ranges, was used to describe and analyze the data based on the normality of the distribution. The ratios of concentration of morphine and morphine to codeine were found to be the possible criteria to distinguish heroin users from codeine users in Chinese people.

Topics: Administration, Oral; Adolescent; Adult; Analgesics, Opioid; Asian People; Biomarkers; Biotransformation; Calibration; China; Chromatography, Liquid; Codeine; Female; Heroin; Heroin Dependence; Humans; Male; Morphine; Predictive Value of Tests; Reference Values; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Substance Abuse Detection; Tandem Mass Spectrometry; Young Adult

Existing incidence estimates of heroin use are usually based on one information source. This study aims to incorporate more sources to estimate heroin use incidence trends in Spain between 1971 and 2005.. A multi-state model was constructed, whereby the initial state "heroin consumer" is followed by transition to either "admitted to first treatment" or to "left heroin use" (i.e. permanent cessation or death). Heroin use incidence and probabilities of entering first treatment ever were estimated following a back-calculation approach.. The highest heroin use incidence rates in Spain, around 1.5 per 1,000 inhabitants aged 10-44, occurred between 1985 and 1990; subdividing by route of administration reveals higher incidences of injection between 1980 and 1985 (a mean of 0.62 per 1.000) and a peak for non-injectors in 1990 (0.867 per 1,000).. A simple conceptual model for heroin users' trajectories related to treatment admission, provided a broader view of the historical trend of heroin use incidence in Spain.

Topics: Adolescent; Adult; Cross-Sectional Studies; Emergency Service, Hospital; Heroin; Heroin Dependence; Humans; Incidence; Likelihood Functions; Middle Aged; Poisson Distribution; Population Surveillance; Spain; Substance Abuse, Intravenous; Young Adult

It has been proposed that the reinforcing properties of drugs of abuse are due, in part, to their ability to enhance memory consolidation. To test this hypothesis, heroin (0.03-3 mg/kg, SC) and d-amphetamine (0.5-2 mg/kg, SC) were administered to male Sprague-Dawley rats immediately or 4 h after training on win-stay and fear conditioning tasks. On the win-stay, immediate post-training administration of lower doses of heroin and d-amphetamine enhanced acquisition, and probe tests further revealed that these drugs enhanced different aspects of learning. Higher doses had no effect or impaired performance, particularly when administered repeatedly. On fear conditioning, the memory-enhancing effects of immediate post-training administration of lower heroin and d-amphetamine doses were revealed only when a single tone-shock pairing procedure was employed. Therefore, under appropriate experimental conditions, mildly stimulatory doses of heroin and d-amphetamine enhanced the acquisition of tasks thought to involve different types of learning. These results support the hypothesis that one of the ways in which drugs of abuse such as opiates and psychomotor stimulants reinforce behavior is by enhancing memory consolidation processes.

Topics: Amphetamine-Related Disorders; Animals; Avoidance Learning; Behavior, Animal; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Heroin; Heroin Dependence; Locomotion; Male; Maze Learning; Memory, Long-Term; Memory, Short-Term; Narcotics; Nootropic Agents; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology

The aim of the present study was to investigate the effects of pretreatment with risperidone on heroin self-administration and heroin-seeking behaviour induced by cues and heroin priming. Rats were trained to self-administer heroin under a fixed ratio 1 schedule for 2 wk and nose-poke responding was extinguished for 10 d, after which reinstatement of drug seeking was induced by conditioned cues or heroin priming. Acute risperidone administration at doses 10-100 μg/kg potently and dose-dependently inhibited reinstatement of conditioned cue-induced heroin seeking; the minimum dose of inhibition was 30 μg/kg. In contrast, risperidone at the same doses did not attenuate reinstatement induced by two priming doses of heroin (100 or 250 μg/kg s.c.). Risperidone at these doses failed to alter heroin self-administration and locomotion activity. These data demonstrate that acute treatment with low-dose risperidone inhibits conditioned cue-induced heroin seeking and risperidone may be an adjunctive therapy for the treatment of heroin addiction.

Topics: Analgesics, Opioid; Animals; Conditioning, Operant; Cues; Disease Models, Animal; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Extinction, Psychological; Heroin; Heroin Dependence; Male; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Risperidone; Secondary Prevention; Self Administration

To characterize the demographic, clinical, and epidemiologic features of levamisole-associated neutropenia in cocaine or heroin users.. State health departments were recruited for participation when the Centers for Disease Control and Prevention (CDC) was notified of potential cases by a clinician, a health department official, or a poison center between October 15, 2009, and May 31, 2010. A case was defined as a person with an absolute neutrophil count less than 1,000 cells/μL (or a WBC count <2,000 cells/μL) and a self-reported history or laboratory confirmation of cocaine or heroin use. Health department officials abstracted data from medical charts, attempted a patient interview, and submitted data to CDC for descriptive analysis.. Of the 46 potential cases reported from 6 states, half met eligibility criteria and had medical chart abstractions completed (n=23; 50%). Of these, close to half of the patients were interviewed (n=10; 43%). The average age was 44.4 years; just over half were men (n=12; 52%). The majority of patients presented to emergency departments (n=19; 83%). More than half presented with infectious illnesses (n=12; 52%), and nearly half reported active skin lesions (n=10; 44%). The majority of interview respondents used cocaine greater than 2 to 3 times a week (n=9; 90%), used cocaine more than 2 years (n=6; 60%), and preferred crack cocaine (n=6; 60%). All were unaware of exposure to levamisole through cocaine and of levamisole's inherent toxicity (n=10; 100%).. Physicians should suspect levamisole exposure in patients using illicit drugs, cocaine in particular, who present with unexplained neutropenia. Most patients reported chronic cocaine use and were unaware of levamisole exposure. Cocaine use is more prevalent among men; however, our results identified a higher-than-expected proportion of female users with neutropenia, suggesting women may be at higher risk. Emergency physicians and practitioners are uniquely positioned to recognize these patients early during their hospital course, elucidate a history of cocaine or other drug exposure, and optimize the likelihood of confirming exposure by arranging for appropriate drug testing.

Topics: Adult; Cocaine; Cocaine-Related Disorders; Drug Contamination; Female; Heroin; Heroin Dependence; Humans; Interviews as Topic; Levamisole; Male; Middle Aged; Neutropenia; Population Surveillance; United States

HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed, and executive function in the multicenter Women's Interagency HIV Study.. Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age = 42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test-Revised and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n = 140), former users (lifetime cocaine or heroin use but not in past 6 months, n = 651), and nonusers (no lifetime use of cocaine or heroin, n = 604).. The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (P < 0.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared with nonuse) negatively impacted verbal learning and memory only in HIV-infected women (P < 0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test.. The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks.

Topics: Adult; Aged; Black or African American; Cocaine-Related Disorders; Cognition; Crack Cocaine; Executive Function; Female; Heroin; Heroin Dependence; HIV Infections; Humans; Illicit Drugs; Memory; Middle Aged; Sex Factors; Verbal Learning; Young Adult

Although self reports of illicit drug use may not be reliable, this information is frequently collected and relied upon by national drug surveys and by counselors in drug treatment programs. The addition of oral fluid testing to these programs would provide objective information on recent drug use.. The goal of this study was to compare oral fluid tests for cocaine, benzoylecgonine, 6-acetylmorphine, morphine, codeine and 6-acetylcodeine to self reports of recent cocaine and heroin use by patients in an outpatient methadone treatment program.. Patients (n=400) provided an oral fluid specimen and completed a short questionnaire on illicit drug use over the last seven days. Oral fluid was collected with the Intercept Oral Fluid Collection device. Oral fluid was analyzed by a validated assay using liquid chromatography coupled with tandem mass spectrometry. The presence of an analyte was confirmed if all identification criteria were met and its concentration (ng/mL) was ≥ LOQ (cocaine, 0.4; benzoylecgonine, 0.4; morphine, 2; codeine, 2; 6-acetylmorphine, 0.4; and 6-acetylcodeine, 1).. Analyses of oral fluid specimens collected from the 400 methadone maintained patients revealed that a majority (95%) of subjects who admitted to recent cocaine use were confirmed positive, whereas slightly more than 50% were confirmed positive who admitted to heroin over the last seven days. For those patients who denied recent cocaine and heroin use, approximately 30% were positive for cocaine and 14% were positive for heroin.. Oral fluid testing provides an objective means of verifying recent drug use and for assessment of patients in treatment for substance use disorders.

Topics: Cocaine; Cocaine-Related Disorders; Codeine; Heroin; Heroin Dependence; Humans; Methadone; Morphine; Morphine Derivatives; Narcotics; Opiate Substitution Treatment; Saliva; Self Report; Substance Abuse Detection

Currently, there are no existing procedures that model in animals the situation where exposure to prolonged mild food restriction results in relapse to drug abuse. Here, reinstatement of extinguished heroin-seeking behavior was assessed in rats under extinction conditions. Ten, but not 7, days of food restriction (∼80% of sated body weight) induced reinstatement of heroin seeking, over and above the spontaneous recovery of the behavior. It is suggested that chronic, mild, food restriction following extinction of drug seeking behavior might serve as a useful model to study the increased risk for relapse to drug abuse due to dietary challenges.

Topics: Animals; Conditioning, Psychological; Disease Models, Animal; Drug-Seeking Behavior; Extinction, Psychological; Food Deprivation; Heroin; Heroin Dependence; Male; Narcotics; Rats; Recurrence; Self Administration; Time Factors

Topics: Botulinum Antitoxin; Botulism; Diagnosis, Differential; Female; Heroin; Heroin Dependence; Humans; Injections; Middle Aged; Substance Abuse, Intravenous

Serious leukoencephalopathy can be related to heroin injection or inhalation.. We report the first case of leukoencephalopathy observed three weeks after a 46-year-old man sniffed heroin. The clinical presentation included cognitive and behaviour disorders, pyramidal irritation and slight gait instability. Blood and cerebrospinal fluid analyse were normal. Brain magnetic resonance imaging showed diffuse, symmetrical supratentorial white matter lesions producing high intense signals on FLAIR and b1000-weighted sequences. Proton spectroscopy revealed an increased rate of cholin, in favour of active demyelinated lesions. Brain biopsy showed intramyelinic oedema with reactive gliosis. After two and a half years, moderate attentional fluctuations and difficulties in initiating activities persisted. Repeated MRI showed a reduction of the leukoencephalopathy.. Heroin could be a cause more common than thought of leukoencephalopathy. The clinical and radiological expression and prognosis could be related to the mode of consummation (inhalation, intravenous injection, sniffing). This parameter may modulate severity and localization of brain lesions. More systematic use of MRI for patients with psychiatric symptoms after heroin intoxications could lead to a better evaluation of heroin-related neurotoxicity and potentially improve prevention.

Topics: Administration, Inhalation; Biopsy; Brain Chemistry; Brain Edema; Choline; Cognition Disorders; Demyelinating Diseases; Gliosis; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Middle Aged; Narcotics; Prognosis

Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin's incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence.. Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals' behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded.. Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs.. Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior.

Topics: Animals; Behavior, Addictive; Conditioning, Psychological; Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Male; Motivation; Rats; Rats, Inbred F344; Substance Withdrawal Syndrome

Objective. Acute or chronic heroin abuse has been associated with various central neurologic pathologies and, occasionally, with peripheral nervous system damage. The effect of heroin on hearing has not been adequately documented, although several cases with sudden hearing loss owed to heroin abuse have been reported. We present a young male with bilateral sudden sensorineural hearing loss, following heroin sniffing and alcohol consumption. Methods. Our patient underwent a detailed clinical and audiological evaluation, including auditory brainstem responses and otoacoustic emission. Routine laboratory blood tests and imaging studies were performed. Results. The patient was treated with corticosteroids and magnesium, resulting in complete restoration of hearing after one month. Conclusion. Sudden hearing loss owed to heroin abuse is usually curable, following adequate treatment.

Topics: Adult; Alcoholism; Audiometry; Central Nervous System Depressants; Ethanol; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Bilateral; Hearing Loss, Sudden; Heroin; Heroin Dependence; Humans; Male; Otoacoustic Emissions, Spontaneous

Food deprivation (FD) or restriction augments the locomotor activating and reinforcing effects of drugs of abuse. It has been proposed that these effects might be mediated by FD-induced increase in plasma levels of ghrelin, a 28-amino acid orexigenic peptide demonstrated to functionally interact with the mesolimbic dopaminergic system. However, a role for ghrelin has been demonstrated only with psychostimulant drugs and alcohol associated behaviors. We therefore examined the role of ghrelin in ongoing heroin self-administration and FD-induced reinstatement of extinguished heroin seeking. As expected, infusions of ghrelin [0.0, 1.5 and 3.0 µg/rat, intracerebroventricular (i.c.v.)] produced increases in breakpoints on a progressive ratio schedule of heroin reinforcement. In contrast, central administration of a ghrelin receptor antagonist, [D-Lys-3]-GHRP-6 (0.0, or 20.0 µg/rat, i.c.v.) had no effect on ongoing heroin self-administration under a fixed-ratio 1 schedule, or on FD-induced reinstatement of heroin seeking. These results suggest that signals mediated through ghrelin receptors play a limited role in FD-induced augmentation of heroin reinforcement and reinstatement of extinguished heroin seeking.

Topics: Animals; Conditioning, Operant; Cues; Extinction, Psychological; Food Deprivation; Ghrelin; Heroin; Heroin Dependence; Hormone Antagonists; Male; Motivation; Narcotics; Oligopeptides; Rats; Rats, Long-Evans; Reinforcement, Psychology

Heroin-assisted treatment (HAT) is a solution for improving the condition of treatment-resistant heroin addicts. Since 1994, six randomized controlled trials have concluded that HAT is more efficacious than oral methadone for severe heroin addicts. We visited seven HAT treatment centres in four countries in order to observe diacetylmorphine (DAM) administration and to study the main concerns of the staff. Nurses were concerned by the risk taken if a previously intoxicated patient received his dose of DAM. Another concern was the smuggling of DAM doses. The HAT centres face a dilemma: treating patients while at the same time allowing their risky street habits in the centre.

Topics: Ambulatory Care; Drug Overdose; Heroin; Heroin Dependence; Humans; Interviews as Topic; Psychiatric Nursing; Security Measures; Substance Abuse Treatment Centers

The study examined concurrent illicit heroin use among methadone maintenance clients in China and its association with clients' demographic characteristics, treatment experience, and personal social network.. Face-to-face surveys were conducted with 178 clients randomly recruited from six methadone maintenance treatment (MMT) clinics in Sichuan, China. Concurrent heroin use was measured based on self-report of heroin use during the past 30 days and a confirmatory urine morphine test. The participants' demographic characteristics and treatment factors were measured and examined. The drug use status of their family members and friends was also assessed.. A total of 80 participants (44.9%) who either reported illicit heroin use in the past 30 days or had a positive urine test were defined as using heroin concurrently. Having drug-using friends was significantly associated with increased concurrent heroin use. Longer length of treatment (2 years or longer) was associated with increased concurrent heroin use. Among those who had both drug-using family members and friends, more women (71.4%) than men (50.0%) used heroin. For those who had no drug-using family members or friends, more men (34.8%) than women (20.8%) used heroin.. Study findings indicate an urgent need to address concurrent illicit heroin use among MMT clients. Further examination of the influence of social networks on concurrent drug abuse behavior is encouraged. Results also highlight the importance of understanding gender differences in treatment seeking and behavioral changes, which is crucial to the development of gender-specific treatment strategies.

Topics: Adolescent; Adult; China; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Risk Factors; Self Report; Sex Distribution; Social Support; Socioeconomic Factors; Substance Abuse Treatment Centers; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol. The emergence of mechanical hypersensitivity with heroin and ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and pain-related states may provide insight into mechanisms underlying the transition to drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Topics: Alcoholism; Animals; Cocaine; Cocaine-Related Disorders; Heroin; Heroin Dependence; Hyperalgesia; Male; Pain Perception; Pain Threshold; Physical Stimulation; Pyrimidines; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Reward; Self Administration

This study examined associations between mortality and demographic and risk characteristics among young injection drug users in San Francisco, California, and compared the mortality rate with that of the population. A total of 644 young (<30 years) injection drug users completed a baseline interview and were enrolled in a prospective cohort study, known as the UFO ("U Find Out") Study, from November 1997 to December 2007. Using the National Death Index, the authors identified 38 deaths over 4,167 person-years of follow-up, yielding a mortality rate of 9.1 (95% confidence interval: 6.6, 12.5) per 1,000 person-years. This mortality rate was 10 times that of the general population. The leading causes of death were overdose (57.9%), self-inflicted injury (13.2%), trauma/accidents (10.5%), and injection drug user-related medical conditions (13.1%). Mortality incidence was significantly higher among those who reported injecting heroin most days in the past month (adjusted hazard ratio = 5.8, 95% confidence interval: 1.4, 24.3). The leading cause of death in this group was overdose, and primary use of heroin was the only significant risk factor for death observed in the study. These findings highlight the continued need for public health interventions that address the risk of overdose in this population in order to reduce premature deaths.

Topics: Adult; Cause of Death; Drug Overdose; Drug Users; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Methamphetamine; Multivariate Analysis; Proportional Hazards Models; Prospective Studies; Risk Factors; San Francisco; Substance Abuse, Intravenous; Young Adult

Once dependent on alcohol or opioids, negative affect may accompany withdrawal. Dependent individuals are hypothesized to "self-medicate" in order to cope with withdrawal, which promotes escalated alcohol and drug use.. The current study aimed to develop a reliable animal model to assess symptoms that occur during spontaneous alcohol and opioid withdrawal.. Dependence was induced using intermittent alcohol exposure or pulsatile heroin delivery and assessed for the presence of withdrawal symptoms during acute withdrawal by measuring somatic signs, behavior in the forced swim test (FST), and air-puff-induced 22-kHz ultrasonic vocalizations (USVs). Additional animals subjected to 8 weeks of alcohol vapor exposure were evaluated for altered somatic signs, operant alcohol self-administration, and 22-kHz USV production, as well as performance in the elevated plus maze (EPM).. During spontaneous withdrawal from pulsatile heroin or intermittent alcohol vapor, animals displayed increased somatic withdrawal signs, FST immobility, and 22-kHz USV production but did not show any behavioral change in the EPM unless the duration of alcohol exposure was extended to 4 weeks. Following 8 weeks of alcohol vapor exposure, animals displayed somatic withdrawal signs, escalated alcohol self-administration, and increased 22-kHz USVs.. These paradigms provide consistent methods to evaluate the behavioral ramifications, and neurobiological substrates, of alcohol and opioid dependence during spontaneous withdrawal. As immobility in the FST and percent open-arm time in the EPM were dissociable, with 22-kHz USVs paralleling immobility in the FST, assessment of air-puff-induced 22-kHz USVs could provide an ethologically valid alternative to the FST.

Topics: Affect; Alcoholism; Animals; Conditioning, Operant; Disease Models, Animal; Ethanol; Heroin; Heroin Dependence; Male; Maze Learning; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome; Swimming; Time Factors; Vocalization, Animal

The objective of this study was to explore the characteristics of comorbid psychiatric symptoms and the relationship between different routes of drug administration and psychiatric symptoms. Five hundred and nine heroin addicts were studied in Drug Detoxification and Rehabilitation Centers in Yunnan and Heilongjiang provinces of China. The measure instrument, including demographic characteristics, history of drug abuse, and the Symptom Checklist-90 (SCL-90) scale (Chinese version), was administered to eligible heroin addicts. Among the subjects, comorbid psychopathology conditions were more severe on all dimensions of SCL-90 comparing with normal adults and the average score of Depression was highest among the 9 dimensions in heroin addicts; psychiatric symptoms were more severe in heroin injecting group than in "chasing the dragon" group and only the difference in Obsessive-Compulsive was significant, but more significant differences were found between snorting heroin addicts and chasing or injecting heroin addicts, and the average score of each dimension of SCL-90 was higher in the snorting group than in the other 2 groups. The reasons of the results and meaning for the present study are discussed. In summary, comorbid psychiatric symptoms in the heroin addicts were very common and severe and their severity varied with different routes of drug administration, suggesting that routes of drug administration should be considered as an important risk factor to mental health of heroin addicts.

Topics: Adult; Analysis of Variance; China; Comorbidity; Depressive Disorder; Diagnosis, Dual (Psychiatry); Female; Heroin; Heroin Dependence; Humans; Male; Mental Disorders; Psychiatric Status Rating Scales; Substance Abuse, Intravenous

Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT.

Topics: Adult; Anisotropy; Brain; Brain Mapping; Depressive Disorder; Diffusion Tensor Imaging; Female; Heroin; Heroin Dependence; Humans; Male; Memory; Methadone; Middle Aged; Nerve Fibers, Myelinated; Neuropsychological Tests; Prospective Studies; Young Adult

Drug use and relapse involve learned associations between drug-associated environmental cues and drug effects. Extinction procedures in the clinic can suppress conditioned responses to drug cues, but the extinguished responses typically reemerge after exposure to the drug itself (reinstatement), the drug-associated environment (renewal), or the passage of time (spontaneous recovery). We describe a memory retrieval-extinction procedure that decreases conditioned drug effects and drug seeking in rat models of relapse, and drug craving in abstinent heroin addicts. In rats, daily retrieval of drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated drug-induced reinstatement, spontaneous recovery, and renewal of conditioned drug effects and drug seeking. In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence.

Topics: Amygdala; Animals; Behavior, Addictive; Cocaine; Cocaine-Related Disorders; Conditioning, Classical; Conditioning, Operant; Cues; Extinction, Psychological; Heroin; Heroin Dependence; Humans; Male; Memory; Mental Recall; Models, Animal; Prefrontal Cortex; Protein Kinase C; Rats; Rats, Sprague-Dawley; Recurrence; Self Administration; Time Factors

Topics: Europe; Heroin; Heroin Dependence; Humans; Legislation, Drug; Narcotics

Topics: Cost-Benefit Analysis; Evidence-Based Medicine; Germany; Heroin; Heroin Dependence; Humans; Injections, Subcutaneous; Narcotics; Netherlands; Prescription Drugs; Randomized Controlled Trials as Topic; Switzerland; Treatment Outcome

To investigate and compare the integrity of white matter in heroin-addicted and healthy control subjects at different abstinent time using diffusion tensor imaging.. We performed voxelwise analysis of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in 35 currently abstinent heroin abusers who were divided into long-term group (n = 17) and short-term group (n = 18) and 17 healthy volunteers. Measurements of FA and ADC of the identified regions (genu and splenium of corpus callosum, bilateral frontal lobe) were obtained from all subjects.. The FA at callosal splenium was higher in the long-term group than in the short-term group (P < 0.05). The FA at left prefrontal cortex was higher in the short-term group than in the long-term group (P < 0.05). No significant difference in ADC was found among the 3 groups. The education history had a positive correlation with the FA value on the gena of corpus callosum (r = 0.402, P = 0.017). Months of abstinence had a negative correlation with left frontal FA (r = -0.366, P = 0.03) and a positive correlation with splenium FA (r = 0.348, P = 0.04).. Heroin abuse seems to alter white matter microstructure differentially in long-term and short-term heroin addicts. This study will contribute to the current literature by examining the quality of white matter fiber structure in heroin abstinence.

Topics: Adult; Aged; Brain; Corpus Callosum; Diffusion Magnetic Resonance Imaging; Female; Follow-Up Studies; Frontal Lobe; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Male; Middle Aged; Substance Withdrawal Syndrome; Young Adult

To investigate the effects of purine nucleotide on the expressions of follicle-stimulating hormone (FSH) and luteotrophic hormone (LH) and the ultrastructures of the distal somatotrophic and gonadotrophic cells in the pituitary gland of heroin-addicted and -withdrawal rats.. Ninety-two male Wistar rats were randomly divided into a control group (ip saline for 14 d), a nucleotide group (ip AMP and GMP for 10 d), a heroin group (ip heroin for 10 d), a heroin + nucleotide group (ip AMP and GMP + heroin for 10 d), a 3 d withdrawal group (ip heroin for 10 d and killed at 14 d), a 9 d withdrawal group (ip heroin for 10 d and killed at 20 d), a 3 d nucleotide group (ip nucleotide for 3 d after 10 d heroin administration and killed at 14 d), and a 9 d nucleotide group (ip nucleotide for 9 d after 10 d heroin administration and killed at 20 d). Changes in the mRNA expressions of FSH and LH in the pituitary gland of the rats were analyzed by semi-quantitative RT-PCR, and alterations in the ultrastructures of the distal somatotrophic and gonadotrophic cells were observed under the microscope.. The expression of FSH mRNA was significantly increased in the nucleotide, heroin + nucleotide, 3 d nucleotide and 9 d nucleotide groups (0.099 +/- 0.018, 0.177 +/- 0.046, 0.151 +/- 0.030 and 0.184 +/- 0.028) as compared with the control group (0.045 +/- 0.009) (P < 0.01); and so was that of LH mRNA in the heroin + nucleotide, 3 d nucleotide and 9 d nucleotide groups (0.950 +/- 0.169, 0.990 +/- 0.171 and 0.960 +/- 0.147) in comparison with the control group (0.700 +/- 0.099) (P < 0.01). In the heroin group, the nuclei of the distal somatotrophic and gonadotrophic cells exhibited morphological abnormality, unclear membrane, slightly pyknotic matrix, marginal and agglutinated heterochromatin, dilated rough endoplasmic reticula, swollen mitochondria, broken and vacuolated cristae in the cytoplasm, obviously decreased number of secretory granules, and myelin bodies in some cells. However, the heroin + nucleotide group showed no significant changes in the ultrastructures of somatotrophic and gonadotrophic cells compared with the control group.. Short-term use of heroin does not obviously affect the expressions of FSH and LH mRNA in the pituitary gland of rats, while heroin + nucleotide, or nucleotide following heroin withdrawal can enhance their expressions significantly. Heroin damages the ultrastructures of the distal somatotrophic and gonadotrophic cells in the pituitary gland of male rats, and purine nucleotide can diminish or inhibit this damage.

Topics: Animals; Follicle Stimulating Hormone; Gene Expression; Heroin; Heroin Dependence; Luteinizing Hormone; Male; Pituitary Gland; Purine Nucleotides; Rats; Rats, Wistar; Substance Withdrawal Syndrome

An unexpected outbreak of "cheese" heroin, which contained diphenhydramine and usually acetaminophen, began in Dallas around 2004. Onset occurred among youths living in neighborhoods populated by first-generation Hispanic immigrants. Little was known about the problem or the social strengths and deficits of these youth, who were primarily inhalers ("snorters") but at risk of transitioning to injection.. Multiple data sources were used, including surveys, data from emergency departments, law enforcement, treatment programs, and coroner, and interviews with users and key informants.. Among heroin users under age 20, overdose deaths peaked in 2006, the school survey responses to using "cheese" heroin peaked in 2007, and treatment admissions peaked in 2008. Hispanic youth entering treatment were less likely to be injectors and report fewer problems than their Anglo counterparts and they were more likely to live with their families and to be supported by them. Sixty percent of the Hispanic youth had been in treatment previously and only 53% completed treatment. Cocaine and/or benzodiazepines were involved in 32% of the adolescent heroin deaths.. The timely use of multiple data sources enabled this outbreak to be quickly identified and monitored, and the Cheese Heroin Task Force used the collected data to help respond to the problem, although retention in treatment and readmissions remained problematic. Cultural problems including immigration status, language, and misunderstandings about the nature of treatment were barriers to successful treatment outcomes. Completion of treatment as an inhaler is critical to reducing the likelihood of transitioning to injection.

Topics: Acetaminophen; Adolescent; Age Factors; Analgesics, Non-Narcotic; Animals; Data Interpretation, Statistical; Diphenhydramine; Disease Outbreaks; Drug Overdose; Emergency Medical Services; Female; Health Surveys; Heroin; Heroin Dependence; Hispanic or Latino; Histamine H1 Antagonists; Humans; Lactose; Male; Narcotics; Poison Control Centers; Schools; Texas; White People; Young Adult

Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence.. We trained rats to self-administer heroin or saline for 9-10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA (Oprm1). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone's (0-1.0 mg/kg) effect on extinction responding after 1 and 15 days.. Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day.. Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.

Topics: Animals; Brain-Derived Neurotrophic Factor; Cues; Dose-Response Relationship, Drug; Gene Expression Regulation; Heroin; Heroin Dependence; Male; Methyl-CpG-Binding Protein 2; Naloxone; Narcotic Antagonists; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Receptor, trkB; Receptors, Opioid, mu; RNA, Messenger; Self Administration; Time Factors

Topics: Adult; Drug Contamination; Female; Heroin; Heroin Dependence; Humans; Iran; Male; Thallium; Young Adult

Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving.. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed.. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P < 0.01, and r = -0.36, P < 0.01, respectively) and after controlling for the effects of potential confounders (β = -0.38, P < 0.01, and β = -0.42, P < 0.01, respectively).. Cholesterol could be associated with the cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

Topics: Adult; Body Mass Index; Cholesterol; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Motivation; Narcotics; Opiate Substitution Treatment; Recurrence; Risk Factors; Statistics as Topic; Substance Withdrawal Syndrome; Surveys and Questionnaires

In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6 h/d for 10 d) and assessed cue-induced heroin seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin seeking increased from 1 to 14 d and was accompanied by increased Fos expression in ∼12% of OFC neurons. Nonselective inactivation of OFC neurons with the GABA agonists baclofen + muscimol decreased cue-induced heroin seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin seeking after 14 withdrawal days. We trained c-fos-lacZ transgenic rats to self-administer heroin and 11 d later reexposed them to heroin-associated cues or novel cues for 15 min (induction day), followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 d later. Daun02 selectively decreased cue-induced heroin seeking in rats previously reexposed to the heroin-associated cues on induction day but not in rats exposed previously to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving.

Topics: Animals; Baclofen; Behavior, Animal; Buprenorphine; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Conditioning, Operant; Cues; Daunorubicin; Extinction, Psychological; GABA-B Receptor Agonists; Gene Expression Regulation; Glutamate Decarboxylase; Heroin; Heroin Dependence; In Vitro Techniques; Male; Muscimol; Narcotic Antagonists; Neurons; Oncogene Proteins v-fos; Phosphopyruvate Hydratase; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Self Administration

Carbohydrate metabolism disorder in heroin dependence is an issue with long history and contradicting results. The aim of the study was to evaluate basal insulin sensitivity in hepatitis C virus seronegative heroin dependents with normal body mass index, taking into consideration the duration of heroin dependence.. 78 heroin dependents and 32 healthy controls were enrolled in the cross-sectional, prospective study. The dependents were observed in 2 groups: group 1 with dependence duration less than or equal to 3 years and group 2 with more than 3 years. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and β-cell function (HOMA-B%) were used to define basal glucose-insulin homeostasis.. The group with longer dependence duration had HOMA-IR (2.23 ± 3.15) significantly higher compared with the control group (1.23 ± 0.53, P = 0.016) but lower compared with the group with the shorter dependence duration (2.65 ± 2.66, P = 0.024), after adjustment for HOMA-B%, waist circumference, and aspartate aminotransferase. The decrease in HOMA-IR during prolonged heroin addiction was significantly associated with the reduced β-cell function (P < 0.001) and waist circumference (P = 0.004).. Heroin dependence is associated with increased insulin resistance in hepatitis C virus seronegative heroin dependents. Prolonged heroin use is associated with reduction of basal β-cell pancreatic function with decreased insulin resistance controlled for waist circumference, but still inducing significantly decreased basal insulin sensitivity.

Topics: Adult; Body Mass Index; Buprenorphine; Cross-Sectional Studies; Female; Hepatitis C; Heroin; Heroin Dependence; Homeostasis; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Metabolic Syndrome; Models, Theoretical; Narcotics; Opiate Substitution Treatment; Prospective Studies; Republic of North Macedonia; Statistics as Topic; Waist Circumference; Young Adult

An increasing number of heroin addicts-especially young and first-time users-prefer inhaling the drug to intravenous injection. A rare complication of inhaling heroin is the development of a spongiform leukoencephalopathy (HSLE).. Pathological background, symptoms, imaging, and therapeutical options are discussed on the basis of an example case.. Pathophysiologically, a dysfunction of the oligodendrocyte mitochondria is suspected. Three distinct stages based on key symptoms are defined. Patients may remain in one stage, or pass through two, or all three stages. Magnetic resonance imaging (MRI) is necessary for diagnosis. There are few therapeutical options. Antioxidants and coenzyme Q may be beneficial. The disorder is self-limiting in the majority of cases. Complications such as hydrocephalus and diffuse cerebellar swelling may, however, require neurosurgical intervention.. HSLE is a rare occurrence in patients with heroin abuse. The number of undetected cases in drug-related deaths may be high. Clinical appearance may be easily mistaken for withdrawal symptoms.

Topics: Administration, Inhalation; Adult; Apoptosis; Cerebellum; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Image Enhancement; Image Interpretation, Computer-Assisted; Leukoencephalopathies; Magnetic Resonance Imaging; Mitochondria; Narcotics; Neurologic Examination; Neurotoxicity Syndromes; Oligodendroglia; Remission, Spontaneous; Tomography, X-Ray Computed

Opioid dependence is a chronic metabolic brain disease and several individual, sociological and biological factors are implicated in its development. Program (needle exchange, low threshold access to treatment) prevent harms associated with opioid use (HIV, overdose…). Effective treatment involves a set of pharmacological and psychosocial interventions. The benefits of maintenance programmes increase as long as the person remains in treatment (many years). Relapse is a symptom of the disorder or a sign of abstinence failure. Treatment aims to improve quality of life in a comprehensive and individualised assessment.

Topics: Harm Reduction; Heroin; Heroin Dependence; HIV Infections; Humans; Needle-Exchange Programs; Prescription Drug Misuse

Different autoantibodies and immunologic abnormalities have been described in heroin addicts.. dpending on the route of heroin application in heroin addicts to determine: 1) immunoglobulins: IgA, IgG, IgM; 2) complement (C3, C4); 3) some other autoantibodies RF, anti β2GP1 fractions: IgA, IgG, IgM, ANA; 4) CIC; 5)monitoring the cryoglobulin presence; 6) clinical manifestations in cryoglobulin positive heroin addicts. A total of 363 heroin addicts were analyzed after previously completed questionnaire; biochemical analyses of blood and urine; creatinine clearance (eC(Cr)) by Cockcroft-Gault formula; proteinuria; 24-hour proteinuria (Uprot/Ucreat); ECG; toxicological analyses; complement (C3, C4); immunoglobulins IgA, IgG, IgM; rheumatoid factor; cryoglobulins; circulating immune complexes; antiphospholipid antibodies (anti β2GP1: IgA, IgG, IgM); antinuclear antibodies. Male patients were predominating (82.09%). Of them 161 were using intravenous heroin (45.4%). IgA was statistically significantly lower in intravenous heroin addicts. Intravenous heroin addicts contrary to those who inhaled heroin had highly significant levels of IgG, IgM, IgG, antiβ2GP1 cryoglobulins; significantly higher mean values of: RF, anti β2GP1 IgA and IgM. Cryoglobulin positive (CP) heroin addicts compared to cryoglobulin negative (CN) presented significantly more frequently with clinical signs of arthralgia, vasculitis, hematuria; whereas highly significantly were manifested respiratory difficulties, neurological disorders, Raynaud phenomenon, proteinuria, 24-hour proteinuria, highly significantly lower mean values of renal clearance. Intravenous heroin addicts compared to the non-parenteral heroin addicts have shown greater changes in certain parameters of humoral immunity. CP heroin addicts have presented with more frequent clinical manifestations than CN heroin addicts.

Topics: Administration, Inhalation; Adolescent; Adult; Autoantibodies; Cryoglobulinemia; Cryoglobulins; Female; Heroin; Heroin Dependence; Humans; Immunity, Humoral; Injections, Intraventricular; Male; Middle Aged; Monitoring, Physiologic; Young Adult

Retrospective study of urinary heroin outcomes of a cohort (123) of patients commenced on a methadone treatment program. Significantly poorer outcomes were associated with urines positive for cocaine (OR 0.69 CI 0.59-0.81) benzodiazepines (OR 0.7 CI 0.53-0.93) with prescribing of low dose methadone (OR 0.65 CI 0.48-0.87), with urines positive for heroin at time of admission (OR 0.74 CI 0.56-0.97) and with behavioural sanctions (OR 0.8, CI 0.65-0.98). Improved outcomes were associated with granting of take away methadone (OR 1.34 CI 1.1-1.62). with an indication of improved outcomes associated with alcohol positive urines (OR 1.34 CI 0.95-1.9) and increased duration of clinic attendance (OR 1.21 CI 0.99-1.47). On multiple regression analysis low dose methadone (0.07 CI 0.01-0.33) prescribing remained negatively associated with urine heroin outcomes.

Topics: Adult; Cannabinoids; Cocaine; Cohort Studies; Comorbidity; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Inpatients; Male; Methadone; Middle Aged; Outcome Assessment, Health Care; Regression Analysis; Retrospective Studies; Risk Factors; Secondary Prevention; Substance Abuse Detection; Substance Abuse Treatment Centers; Substance-Related Disorders; Young Adult

The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems.

Topics: Animals; Antioxidants; Ceruloplasmin; Glutathione; Heroin; Heroin Dependence; Lipid Peroxidation; Male; Malondialdehyde; Melatonin; Naloxone; Nitrates; Nitrites; Oxidative Stress; Rats; Rats, Sprague-Dawley; Selenium; Substance Withdrawal Syndrome; Vitamin E

The aim of the study was to investigate predictors of offending among prisoners from official records after controlling for age at first conviction and antisocial personality disorder. The participants were 198 Scottish prisoners, who had completed Diagnostic Statistical Manual IV screens for child and adult attention-deficit hyperactivity disorder (ADHD) symptoms and the Millon Clinical Multiaxial Inventory III for Axis I and Axis II disorders. The ADHD symptomatic group had significantly higher rates of total, acquisitive and violent offending than other prisoners, as well as greater regular heroin use. Hierarchical multiple regressions, using child and adult symptoms as dimensions, showed that frequent use of heroin in the year prior to imprisonment was the single most powerful predictor of the extent of total offending, with ADHD symptoms also adding independently to the variance in offending. In contrast, for violent offending, ADHD symptoms were the strongest predictor followed by alcohol dependence. The findings demonstrate the importance of heroin use and ADHD symptoms in the persistence of offending. There is an urgent need to treat drug addiction and ADHD symptoms in order to reduce offending among the most persistent offenders. Recently, treatment programmes have been developed for adults with ADHD, heroin and crack cocaine addiction which can be applied to this population.

Topics: Alcoholism; Antisocial Personality Disorder; Attention Deficit Disorder with Hyperactivity; Criminals; Heroin; Heroin Dependence; Humans; Male; Prisoners; Scotland; Substance-Related Disorders; Surveys and Questionnaires; Violence

Heroin is an illicit narcotic abused by millions of people worldwide. In our earlier studies we have shown that heroin intoxication changes the antioxidant status in human brain. In the present work we continued our studies by estimating the effect of heroin abuse on reduced glutathione (GSH) and enzymes related to this cofactor, such as glutathione S-transferase detoxifying electrophilics (GST) and organic peroxides (as Se-independent glutathione peroxidase-GSHPx), and Se-dependent glutathione peroxidase (Se-GSHPx) specific mainly for hydrogen peroxide. Studies were conducted on human brains obtained from autopsy of 9 heroin abusers and 8 controls. The level of GSH and the activity of glutathione-related enzymes were determined spectrophotometrically. The expression of GST pi on mRNA and protein level was studied by RT-PCR and Western blotting, respectively. The results indicated significant increase of GST and GSHPx activities, unchanged Se-GSHPx activity, and decreased level of GSH in frontal, temporal, parietal and occipital cortex, brain stem, hippocampus, and white matter of heroin abusers. GST pi expression was increased on both mRNA and protein levels, however the increase was lower in brain stem than in other regions. Heroin affects all regions of human brain, and especially brain stem. Its intoxication leads to an increase of organic rather then inorganic peroxides in various brain regions. Glutathione S-transferase plays an important role during heroin intoxication, however its protective effect is lower in brain stem than in brain cortex or hippocampus.

Topics: Antioxidants; Brain; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Heroin; Heroin Dependence; Humans

Opioid overdose risk reduction behaviours include some preventive behaviours to avoid overdoses (PB) and others to avoid death after overdose, such as never using heroin while alone (NUA). Few studies have examined the prevalence and predictors of these behaviours.. To establish the prevalence and predictors of PBs and NUA among heroin users, both injectors and non-injectors, in three Spanish cities.. 516 injecting and 475 non-injecting heroin users aged 18-30 were street-recruited in 2001-2003 and interviewed by face-to-face computer-assisted interview. PBs and NUA in the last 12 months were explored using open-ended and precoded questions, respectively. Specific predictors for three PB categories were investigated: control of route of drug administration, control of quantity or type of heroin used, and control of co-use of other drugs. Bivariate and logistic regression methods were used.. Overall, the most prevalent PBs were: using a stable and not excessive amount of heroin (12.7%), injecting or using the whole heroin dose slowly or dividing it into smaller doses (12.4%), reducing or stopping heroin injection (8.3%), and not mixing heroin with tranquillisers (5.1%). Most PBs were significantly more prevalent among injectors than non-injectors. No one mentioned reducing the amount of heroin after an abstinence period. Some 36.2% had NUA. In multiple regression analysis, knowledge of risk factors for opioid overdose was a predictor of specific PBs, although this was not always the case. Use of syringe exchange programmes was a predictor of PB among injectors. However, attending methadone maintenance treatment (MMT) or other drug-dependence treatment was not a predictor of any opioid overdose reduction behaviour. Only ever having witnessed or experienced an overdose predicted PB in both injectors and non-injectors.. The proportion of heroin users with opioid overdose risk reduction behaviours is very low. Additional specific measures to prevent overdose are needed, as well as increased emphasis on reducing the risk of overdose in programmes to prevent HIV and other blood-borne infections in heroin injectors.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Heroin; Heroin Dependence; HIV Infections; Humans; Male; Risk Factors; Risk Reduction Behavior; Spain; Substance Abuse, Intravenous; Surveys and Questionnaires; Young Adult

Although recent data suggest that some long non-coding RNAs (lncRNAs) exert widespread effects on gene expression and organelle formation, lncRNAs as a group constitute a sizable but poorly characterized fraction of the human transcriptome. We investigated whether some human lncRNA sequences were fortuitously represented on commonly used microarrays, then used this annotation to assess lncRNA expression in human brain. A computational and annotation pipeline was developed to identify lncRNA transcripts represented on Affymetrix U133 arrays. A previously published dataset derived from human nucleus accumbens was then examined for potential lncRNA expression. Twenty-three lncRNAs were determined to be represented on U133 arrays. Of these, dataset analysis revealed that five lncRNAs were consistently detected in samples of human nucleus accumbens. Strikingly, the abundance of these lncRNAs was up-regulated in human heroin abusers compared to matched drug-free control subjects, a finding confirmed by quantitative PCR. This study presents a paradigm for examining existing Affymetrix datasets for the detection and potential regulation of lncRNA expression, including changes associated with human disease. The finding that all detected lncRNAs were up-regulated in heroin abusers is consonant with the proposed role of lncRNAs as mediators of widespread changes in gene expression as occur in drug abuse.

Topics: Analgesics, Opioid; Brain Chemistry; Data Mining; Gene Expression Regulation; Genetic Markers; Heroin; Heroin Dependence; Humans; Nucleus Accumbens; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Reward; RNA, Untranslated; Up-Regulation

Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were paired with a tone-light cue) and tested for cue-induced heroin-seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time-dependent increases in extinction responding were associated with time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens. Additionally, acute accumbens (but not VTA) GDNF injections (12.5 µg/side) administered 1-3 hours after the last heroin self-administration training session enhanced the time-dependent increases in extinction responding after withdrawal. However, the time-dependent increases in extinction responding after withdrawal were not associated with changes in GDNF protein expression in VTA and accumbens. Additionally, interfering with endogenous GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies (600 ng/side/day) into VTA or accumbens had no effect on the time-dependent increases in extinction responding. In summary, heroin self-administration and withdrawal regulate VTA and accumbens GDNF mRNA expression in a time-dependent manner, and exogenous GDNF administration into accumbens but not VTA potentiates cue-induced heroin seeking. However, based on the GDNF protein expression and the anti-GDNF monoclonal neutralizing antibodies manipulation data, we conclude that neither accumbens nor VTA endogenous GDNF mediates the incubation of heroin craving.

Topics: Animals; Association Learning; Cues; Extinction, Psychological; Glial Cell Line-Derived Neurotrophic Factor; Heroin; Heroin Dependence; Male; Narcotics; Nucleus Accumbens; Rats; Rats, Long-Evans; RNA, Messenger; Substance Withdrawal Syndrome; Ventral Tegmental Area

Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.. This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination ("speedball").. Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin-cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge.. Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking.. A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.

Topics: Animals; Behavior, Addictive; Cocaine; Cocaine-Related Disorders; Dominance-Subordination; Drug Synergism; Heroin; Heroin Dependence; Male; Motor Activity; Rats; Rats, Long-Evans; Reinforcement Schedule; Reinforcement, Psychology; Self Administration; Stress, Psychological

Hunger strike of prisoners and detainees remains a major human rights and ethical issue for medical professionals. We are reporting on a case of a 48-year-old male sentenced prisoner, intravenous heroin user, who went on a hunger strike and died 15 days later. Throughout the fasting period, the prisoner, who was capable of decision making, refused any medical examination. Autopsy findings were not supporting prolonged starvation, while toxicology revealed benzodiazepines and opiates in blood and urine. Cause of death was given as "heroin intoxication" in keeping with detection of 6-MAM. Legal and ethical issues pertinent to medical examination and treatment of prisoners on hunger strike are explored in accordance with legislation and professional ethical standards in Serbia. A recommendation for the best autopsy practice in deaths following hunger strike has been made.

Topics: Carbamazepine; Codeine; Dissent and Disputes; Fasting; Forensic Toxicology; Heroin; Heroin Dependence; Humans; Liver Cirrhosis; Male; Middle Aged; Morphine; Morphine Derivatives; Narcotics; Prisoners; Serbia

In a rat model of context-induced relapse to heroin, we identified sparsely distributed ventral medial prefrontal cortex (mPFC) neurons that were activated by the heroin-associated context. Selective pharmacogenetic inactivation of these neurons inhibited context-induced drug relapse. A small subset of ventral mPFC neurons formed neuronal ensembles that encode the learned associations between heroin reward and heroin-associated contexts; re-activation of these neuronal ensembles by drug-associated contexts during abstinence provoked drug relapse.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Heroin; Heroin Dependence; Nerve Net; Neurons; Prefrontal Cortex; Rats; Secondary Prevention; Substance Withdrawal Syndrome

Topics: Administration, Inhalation; Brain; Cerebellum; Dysarthria; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Nystagmus, Pathologic; Smoke; Substance Abuse, Intravenous; Young Adult

Risk factors for osteoporosis are prevalent in chronic heroin users who often start using opiates in their late teens. This study was the first to evaluate bone mineral density (BMD) in relatively young heroin-dependent patients on injectable heroin maintenance.. Using cross-sectional design, BMD was assessed in a convenience sample of 19 patients (mean age ± SD = 33.9 ± 5.4; 13 men) prescribed injectable diacetylmorphine for heroin dependence. BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry. Substance use and menstrual history, psychopathology and risk factors for low BMD were assessed by questionnaire-based interviews.. According to World Health Organisation criteria almost three-quarters (74%) of the sample had osteopenia (n = 11) or osteoporosis (n = 3) at one or more sites of measurement. All patients showed multiple risk factors for bone loss, with pack-years of tobacco use and years of heroin use reaching marginally significant associations with spine Z-scores. Moreover, BMD Z-scores correlated significantly negatively with increasing age at all sites, indicating that the older the patient, the greater the BMD deviation from an age-controlled population.. Prolonged heroin dependence appears to be associated with lower-than-normal bone mass already at early age and these individuals might be at greater risk for fracture with advancing age. The negative correlation of age-adjusted Z-scores with increasing age suggests factors other than age for low BMD in this population (e.g. smoking, heroin use). Prospective studies are warranted to determine the necessity for diagnostic and preventive measures.

Topics: Adult; Bone Density; Cross-Sectional Studies; Female; Femur; Heroin; Heroin Dependence; Humans; Lumbar Vertebrae; Male; Narcotics; Osteoporosis; Radiography

Vagus nerve stimulation has been used for the treatment of neuropsychiatric disorders, such as epilepsy. However, little is known whether it is also effective for the treatment of heroin dependence, in particular for relapse to heroin seeking. In the present study, we investigated the effects of vagus nerve stimulation on reinstatement (relapse) of heroin-seeking behavior induced by heroin priming or heroin-associated cues. The rats were trained for heroin self-administration for 14days and followed by extinction training in which heroin was replaced by saline and heroin-associated cues were turned off. In addition, animals were also received daily electric stimulation of vagus nerve (30Hz, pulse width of 0.5ms, 0.5mA (low-intensity) or 1mA (high-intensity); 30s on, 5min off; 10 continuous cycle per day) or false stimulation during extinction training. We found that such vagus nerve stimulation significantly inhibited heroin priming (0.25mg/kg, s.c.) - or heroin-associated conditioned cue-induced reinstatement of drug-seeking behavior, when compared to false stimulation control. Further, such a behavioral inhibition was correlated to a reduction in the expression of FosB and an increase in the expression of phosphorylation of cAMP response element binding protein (p-CREB) in nucleus accumbens. The data suggest that vagus nerve stimulation may inhibit heroin- or heroin cue-induced relapse, possibly by regulation of the expression of Fos and CREB in nucleus accumbens.

Topics: Analysis of Variance; Animals; Behavior, Animal; Blotting, Western; Cues; Cyclic AMP Response Element-Binding Protein; Drug-Seeking Behavior; Extinction, Psychological; Heroin; Heroin Dependence; Male; Narcotics; Nucleus Accumbens; Phosphorylation; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Self Administration; Vagus Nerve Stimulation

Methadone maintenance treatment (MMT) might cause the impairments of neuropsychological and neurotransmitter function in opioid addicts. Whether long-term MMT could lead to the impairment of white matter (WM) in heroin addiction brain is unclear. This study compared the WM integrity in the bilateral frontal lobe, temporal lobe, splenium and genu of corpus collasum (CC) between MMT patients (n=13), former heroin addicts (n=11) in prolonged abstinence (PA), and healthy control subjects (n=15) using diffusion tensor imaging (DTI). Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and eigenvalues (λ(⊥), λ(||)) were measured. The correlation between DTI measures and accumulated former heroin dose, total methadone consumption, and PA duration were determined. Although the PA subjects showed no difference in DTI measures relative to the controls, the extensive correlations between the former heroin consumption and the DTI measures were noted. The MMT subjects showed a decreased FA values in the left genu, as well as the increased ADC and λ(⊥) values in the left splenium of CC in comparison to the controls. Compared with the PA, the MMT subjects had a significantly increased ADC value in the bilateral splenium of CC. Importantly, the methadone dosage used in the MMT group was correlated with the FA value in the left splenium of CC and in the right frontal lobe. Our preliminary results suggest that methadone plays a role in the impairment of WM integrity in heroin users on long-term MMT and the normalization of WM injury may occur during abstinence.

Topics: Adult; Anisotropy; Brain; Diffusion Tensor Imaging; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Nerve Fibers, Myelinated; Regression Analysis

The prevalence of opioid abuse and dependence has been on the rise in just the past few years. Animal studies indicate that extended access to heroin produces escalation of intake over time, whereas stable intake is observed under limited-access conditions. Escalation of drug intake has been suggested to model the transition from controlled drug use to compulsive drug seeking and taking. Here, we directly compared the pattern of heroin intake in animals with varying periods of heroin access. Food intake was also monitored over the course of escalation. Rats were allowed to lever press on a fixed-ratio 1 schedule of reinforcement to receive intravenous infusions of heroin for 1, 6, 12, or 23h per day for 14 sessions. The results showed that heroin intake in the 12 and 23h groups markedly increased over time, whereas heroin intake in the 1h group was stable. The 6h group showed a significant but modest escalation of intake. Total heroin intake was similar in the 12 and 23h groups, but the rate of heroin self-administration was two-fold higher in the 12h group compared with the 23h group. Food intake decreased over sessions only in the 12h group. The 12 and 23h groups showed marked physical signs of naloxone-precipitated withdrawal. These findings suggest that 12h heroin access per day may be the optimal access time for producing escalation of heroin intake. The advantages of this model and the potential relevance for studying drug addiction are discussed.

Topics: Animals; Behavior, Animal; Disease Models, Animal; Drug-Seeking Behavior; Heroin; Heroin Dependence; Humans; Male; Naloxone; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome; Time Factors

This study aims to asses the influence of inhalable heroin on pulmonary function in chronic heroin-dependent patients treated with inhalable heroin. Among 32 patients (all cigarette smokers), a spirometric test was conducted at baseline and after an average period of 10 months of treatment with medically prescribed heroin. Patients showed a high frequency of pulmonary dysfunction at baseline [34%, with percentage of forced expiratory volume in 1 s (%FEV1)<80%]. However, after excluding those who started pulmonary treatment (n=2) or who used heroin intravenously only (n=2), no statistically significant differences in %FEV1 between baseline and follow-up were observed (n=28; mean %FEV1 86% at baseline vs. 91% at follow-up; p=0.09). This small and relatively brief study suggests that 10 months of co-prescribed inhalable heroine base does not seem to (further) deteriorate pulmonary function in chronic, cigarette smoking treatment refractory heroin addicts. Screening for and treatment of pulmonary dysfunction is recommended for methadone patients with and without co-prescribed heroin.

Topics: Administration, Inhalation; Adult; Female; Follow-Up Studies; Forced Expiratory Volume; Heroin; Heroin Dependence; Humans; Lung; Male; Prospective Studies; Respiratory Function Tests; Treatment Outcome

Semi-structured interviews were used to assess behavioral economic drug demand in heroin dependent research volunteers. Findings on drug price, competing purchases, and past 30-day income and consumption, established in a previous study, are replicated. We extended these findings by having participants indicate whether hypothetical environmental changes would alter heroin purchasing. Participants (n = 109) reported they would significantly (p < .005) decrease heroin daily purchasing amounts (DPA) from past 30-day levels (M = $60/day) if: (a) they encountered a 33% decrease in income (DPA = $34), (b) family/friends no longer paid their living expenses (DPA = $32), or (c) they faced four-fold greater likelihood of police arrest at their purchasing location (DPA = $42). Participants in higher income quartiles (who purchase more heroin) show greater DPA reductions (but would still buy more heroin) than those in lower income quartiles. For participants receiving government aid (n = 31), heroin purchasing would decrease if those subsidies were eliminated (DPA = $28). Compared to participants whose urine tested negative for cocaine (n = 31), cocaine-positive subjects (n = 32) reported more efficient heroin purchasing, that is, they live closer to their primary dealer; are more likely to have heroin delivered or walk to obtain it (and less likely to ride the bus), thus reducing purchasing time (52 vs. 31 min, respectively); and purchase more heroin per episode. These simulation results have treatment and policy implications: Daily heroin users' purchasing repertoire is very cost-effective, more so for those also using cocaine, and only potent environmental changes (income reductions or increased legal sanctions) may impact this behavior.

Topics: Adult; Commerce; Female; Heroin; Heroin Dependence; Humans; Income; Male; Middle Aged

As a result of long-term heroin abuse we can see impairment of cerebral structures, that leads to specific psychopathological and neuro - physiological deficits in the cognitive and connative areas. There is a positive correlation between the mentioned deficits and the duration of heroin abuse. The memory is a cognitive function highly sensitive to toxic effects of opiates. The aim of this study was to establish the psychiatric and psychological consequences of heroin abuse, in the sense of verbal memory deficits, and the specific relation between mentioned deficits with the duration of abuse.. The research was devised as a prospective study, including ninety heroin addicts, divided into three groups, based on the abuse duration. The following instruments were used for data collecting: questionnaire, with basic social-demographic and addictive characteristics of subjects and Rey Test of Verbal Learning, a neuropsychological test for verbal memory estimation.. Only the examinees who have abused heroin for less than a year obtained scores within the domain of the expected performances within the part of the test which relates to the direct verbal memory, as well as, the part of the test that relates to delayed verbal memory. With regard to the mentioned criteria, the difference between examinees with different length of opiates abuse is statistically important (direct memory: F=2.706; p=0.063, delayed memory: F=2.538; p=0.045). With the increase of heroin abuse length the number of examinees with a rising learning curve is decreased significantly, and the number of examinees with a flat learning curve is increased (Chi-square=19.589; p=0.003).. Heroin abuse, lasting longer than one year, is connected with impairment of short-term and delayed verbal memory. The intensity of the mentioned effects is higher with addicts who use a higher daily dose of heroin.

Topics: Adult; Dose-Response Relationship, Drug; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Memory, Short-Term; Narcotics; Neuropsychological Tests; Prospective Studies; Psychometrics; Retention, Psychology; Time Factors; Verbal Learning; Wechsler Scales; Young Adult

This paper examines changes in the interval between first heroin smoking and onset of injection in a large, out-treatment sample of male heroin users in Hanoi, Vietnam (n = 1,115). Mean age at initiation of heroin use (smoking) was 18.4 and mean age of onset of heroin injection was 20.9 years. Full multivariate analysis indicates that the interval between first heroin use (smoking) and first heroin injection has been significantly attenuated among more recent heroin initiates (P = 0.0043), suggesting that heroin users in Vietnam may be at increased risk for exposure to HIV relatively soon after onset of heroin use, highlighting the need for behavioral interventions that target heroin smokers. Critical intervention goals include delaying the onset of injection and improved education about safer drug sharing and drug injection practices.

Topics: Administration, Inhalation; Adolescent; Adult; Age of Onset; Cross-Sectional Studies; Disease Progression; Harm Reduction; Heroin; Heroin Dependence; HIV Infections; Humans; Injections, Intravenous; Male; Smoking; Substance Abuse, Intravenous; Time Factors; Vietnam; Young Adult

Topics: Heroin; Heroin Dependence; Humans; Methadone; Narcotics

Non-prescribed use of pharmaceutical opioid analgesics (POA) has been escalating internationally. In Australia, few studies have examined if POA users have similar characteristics and treatment needs to heroin users. The aim of this study was to compare those presenting for treatment where heroin versus POA were the primary drugs of concern.. A convenience sample of 192 treatment entrants were recruited from alcohol and drug treatment services in four Australian jurisdictions. A structured interview collected data on demographic characteristics, substance use, self-perceived mental and physical health, crime and harms resulting from drug use. Multivariate analyses were performed to identify characteristics which may differentiate those seeking treatment for heroin compared with POA.. Most treatment entrants sampled reported a history of injection drug use and use of both heroin and POA. However, those with primary POA problems were less likely to report an overdose history (adjusted odds ratio 0.90, 95% confidence interval 0.81-0.99) and more likely to initiate opioid use for pain (adjusted odds ratio 2.52, 95% confidence interval 1.04-6.12) than those with primary heroin problems. Latent Class Analysis found that, while most of the POA group were similar to heroin users in demographics, health and injecting drug use, there was a small, distinct group of primary POA problem users that did not typically inject and who commonly initiated opioid use for pain and also experienced elevated physical and mental health disability.. While some differences existed, this study of Australian treatment seekers found many similar characteristics between those with primary problems with heroin and POA. Few non-injecting POA were recruited in this sample. This finding contrasts with reports of a growing population of opioid-dependent people with characteristics that are distinct from traditional opioid-dependent populations, which may reflect the orientation of current treatment systems in Australia towards injection drug users.

Topics: Adolescent; Adult; Analgesics, Opioid; Australia; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Opioid-Related Disorders; Patient Acceptance of Health Care; Self Report; Young Adult

Previous functional imaging studies on heroin addicts have focused on abnormal brain functions based on specific tasks, while few fMRI studies concentrated on the resting-state abnormalities of heroin-dependent individuals. In the current study, we applied the pattern classification technique, which employs the feature extraction method of non-negative matrix factorization (NMF) and a support vector machine (SVM) classifier. Its main purpose was to characterize the discrepancy in activation patterns between heroin-dependent individuals and healthy subjects during the resting state. The results displayed a high accuracy in the activation pattern differences of the two groups, which included the orbitofrontal cortex (OFC), cingulate gyrus, frontal and para-limbic regions such as the anterior cingulate cortex (ACC), hippocampal/parahippocampal region, amygdala, caudate, putamen, as well as the posterior insula and thalamus. These findings indicate that significant biomarkers exist among the network of circuits that are involved in drug abuse. The implications from our study may help explain the behavioral and neuropsychological deficits in heroin-dependent individuals and shed light on the mechanisms underlying heroin addiction.

Topics: Adult; Biomarkers; Brain Mapping; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Models, Neurological; Narcotics; Rest

The high prevalence of cigarette smoking among heroin users has triggered many studies to explore possible interactions between cigarette smoking and heroin addiction; however, little is known about the relationship between cigarette smoking behaviors and routes of heroin administration. The present study provided the first examination of cigarette smoking status, motivation, and cigarette smoking cue reactivity among injecting or inhaling heroin users.. Forty-six heroin-dependent patients were recruited in the present study. A battery of self-report questionnaires was used to assess cigarette smoking status and the reasons for smoking. In the clinical laboratory study, participants completed a cue-reactivity procedure that involved collecting psychophysical and motivational data in response to cigarette smoking slides.. The average number of cigarette per day among heroin inhalers was higher than that among heroin injectors. Most heroin inhalers reported that the primary reason for smoking was "maintaining drug pleasure," whereas heroin injectors reported that the primary smoking reason was "nicotine pleasure." Compared with heroin injectors, heroin inhalers provided increased ratings of heroin craving and desire to heroin use when exposed to cigarette smoking cues. Number of cigarettes per day was significantly correlated with cue-induced overall mean motivation in heroin inhalers but not in heroin injectors.. Cigarette smoking behaviors were different among heroin inhalers from among heroin injectors. These results emphasize the stronger association between cigarette smoking and heroin inhaling.

Topics: Administration, Inhalation; Adult; Behavior, Addictive; Cues; Female; Heroin; Heroin Dependence; Hospital Records; Humans; Injections, Intravenous; Male; Middle Aged; Motivation; Prevalence; Self Report; Smoking

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma, we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.

Topics: Animals; Antibody Specificity; Cattle; Drug Carriers; Enzyme-Linked Immunosorbent Assay; Haptens; Hemocyanins; Heroin; Heroin Dependence; Hot Temperature; Immunoconjugates; Male; Molecular Structure; Morphine; Narcotics; Pain; Psychotropic Drugs; Rats; Rats, Wistar; Secondary Prevention; Self Administration; Serum Albumin, Bovine; Structure-Activity Relationship; Touch; Vaccines

The present investigations sought to determine whether the ventral tegmental area (VTA), basolateral amygdala (BLA), and nucleus accumbens shell (NAC) comprise a circuitry that mediates heroin-induced conditioned immunomodulation. Rats were given conditioning trials in which they received an injection of heroin upon placement into a distinctive environment. Prior to testing, rats received unilateral intra-BLA microinfusion of a D(1) antagonist concomitantly with unilateral intra-NAC shell microinfusion of an NMDA antagonist. Disconnection of the VTA-BLA-NAC circuit impaired the ability of the heroin-paired environment to suppress lipopolysaccharide-induced immune responses, defining for the first time a specific neural circuit involved in conditioned neural-immune interactions.

Topics: Amygdala; Analgesics, Opioid; Animals; Conditioning, Psychological; Disease Models, Animal; Heroin; Heroin Dependence; Immunomodulation; Male; Neural Pathways; Nucleus Accumbens; Rats; Rats, Inbred Lew; Ventral Tegmental Area

We investigated the role of histone H3 phosphoacetylation in the nucleus accumbens (NAc) in heroin-conditioned place preference paradigm. Heroin could dose-dependently increase histone H3 phosphoacetylation specifically in the NAc and could enhance heroin place preference. Injection of trichostatin A into the NAc significantly augmented heroin-induced histone H3 phosphoacetylation and enhanced heroin place preference. Conversely, injection of MK-801 into the NAc attenuated histone H3 phosphoacetylation and reduced heroin place preference. These data suggest that histone H3 phosphoacetylation in the NAc may play a critical role in heroin addiction.

Topics: Acetylation; Animals; Brain; Conditioning, Operant; Heroin; Heroin Dependence; Histones; Immunohistochemistry; Male; Narcotics; Phosphorylation; Rats; Rats, Sprague-Dawley

Heroin abuse can lead to organic damage of cerebral structures, including sequels in cognitive and affective sphere, which are in positive relation with the duration of substance usage. Memory is one of the cognitive functions which is highly sensitive to opiate toxic effects. The aim of this research was determination of heroin impact on the visual memory of addicts, as well as the existence of specific relation of potential deficiencies in visual memory with the duration of substance use.. The research included 90 examinees, divided into three groups, depending on the duration of heroin intake. We used questionnaire for basic socio-demographic and addictological traits of examinees; Wechsler's scale for the assessment of the intelligence and Visual Memory Test (TVP), for the assessment of the visual memory.. The achievements of heroin addicts with different duration of the substance abuse differ significantly (F = 1.83; df = 12; p < 0.05). Total number of errors examinees make in the first series of TVP (immediate visual memory) grows, almost linearly in the function of the duration of heroin abuse (p < 0.05), but in neither of groups meets criteria for the visual memory impairment. Deficiency of the delayed visual memory occurs in examinees who use heroin for one (total number of errors = 6.46; participation of typical organic errors = 31.7%) and longer than five years (total number of errors = 7.66; participation of typical organic errors = 26.7%). Univariate covariance analysis separates the average daily dosage of heroin as the most significant variable that contributes to the expression of the aforementioned deficiencies (F = 4.21; df = 2; p < 0.05).. Heroin abuse leads to damage of delayed visual memory, whereby for the observed effect intake of the substance for a period longer than one year is necessary.

Topics: Adult; Heroin; Heroin Dependence; Humans; Male; Memory; Prospective Studies; Visual Perception

This study investigates frequency and types of criminal convictions among a national sample of heroin users during a 3-year period prior to opioid maintenance treatment (OMT). All heroin users (N = 3,789) in Norway who applied for and were eligible for OMT (1997-2003) were included. The OMT records were cross-linked to Norwegian crime statistics. During observation, 24,478 convictions were recorded among 60.9% of the sample. Differences of criminal convictions were found within the group; a large proportion (39.1%) had no convictions, whereas 10% of the sample was responsible for 37.8% of all convictions. Convictions for acquisitive crimes and drug crimes were the most common. Variations in the cohort's individual crime sequences were found. The heavy involvement of heroin users with the criminal justice system provides an opportunity to intervene with dependent offenders. Coordination between treatment providers and police or courts can play an important role in improving outcomes through better access to treatment.

Topics: Adult; Analgesics, Opioid; Cohort Studies; Crime; Criminals; Databases, Factual; Drug Users; Female; Heroin; Heroin Dependence; Humans; Judicial Role; Longitudinal Studies; Male; Methadone; Norway; Opiate Substitution Treatment; Time Factors; Violence

Heroin has been shown to cause spongiform leukoencephalopathy (SLE) in heroin addicts. In this study, we found that heroin could induce apoptosis of primary cultured cerebellar granule cells (CGC) and c-Jun N-terminal kinase (JNK) pathway is activated during CGCs apoptosis. Inhibiting JNK with a specific inhibitor, SP600125, reduced the levels of c-Jun phosphorylation and caspase-3 activation. We also showed that use the JNK inhibitor SP600125, caspase inhibitor z-VAD, or use SP600125 and z-VAD together significantly suppressed cell death induced by heroin. These results indicate that JNK pathway is an important mediator of the neurotoxic effects of heroin and inhibiting JNK activity may represent a new and effective strategy to treat heroin-induced SLE.

Topics: Animals; Animals, Newborn; Apoptosis; Caspase 3; Caspase Inhibitors; Cerebellum; Cytoplasmic Granules; Disease Models, Animal; Enzyme Activation; Heroin; Heroin Dependence; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 8; Narcotics; Neurons; Primary Cell Culture; Rats; Rats, Sprague-Dawley

This article reports the case of a patient demonstrating acute bilateral pneumonitis almost completely confined to the upper lobes as a result of inhaling heroin. We attribute this distribution to the patient performing the Valsalva manoeuvre immediately after inhaling heroin. This pattern has not been reported before and we believe it may be seen more frequently owing to a switch amongst drug users from intravenous to inhaled heroin.

Topics: Acute Disease; Acute Lung Injury; Administration, Inhalation; Blood Gas Analysis; Female; Heroin; Heroin Dependence; Humans; Middle Aged; Pneumonia; Radiography, Thoracic; Valsalva Maneuver

Heroin use has seriously threatened public heath in many countries, but the existing therapies continue to have many limitations. Recently, immunotherapy has shown efficacy in some clinical studies, including vaccines against nicotine and cocaine, but no opioid vaccines have been introduced in clinical studies. The development of a novel opioid antigen designed specifically for the prevention of heroin addiction is necessary. A morphine-keyhole limpet hemocyanin conjugate was prepared and administered subcutaneously in rats. Antibody titers in plasma were measured using an enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was used to assess the selectivity of the antibodies. Dopamine concentrations in the nucleus accumbens in rats after vaccine administration were determined by high-performance liquid chromatography with electrochemical detection. The effects of the vaccine on the heroin-primed restatement of self-administration and locomotor sensitization were evaluated. A novel hapten, 6-glutarylmorphine, was produced, and the vaccine generated a high antibody titer response. This vaccine displayed specificity for both morphine and heroin, but the anti-morphine antibodies could not recognize dissimilar therapeutic opioid compounds, such as buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The morphine antibody significantly decreased morphine-induced locomotor activity in rats after immunization. Importantly, rats immunized with this vaccine did not exhibit heroin-primed reinstatement of heroin seeking when antibody levels were sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens after morphine administration, which is consistent with its behavioral effects. These results suggest that immunization with a novel vaccine is an effective means of inducing a morphine-specific antibody response that is able to attenuate the behavioral and psychoactive effects of heroin.

Topics: Animals; Antibodies; Antibody Specificity; Chromatography, High Pressure Liquid; Conditioning, Operant; Disease Models, Animal; Dopamine; Enzyme-Linked Immunosorbent Assay; Extinction, Psychological; Hemocyanins; Heroin; Heroin Dependence; Male; Motor Activity; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Vaccines, Conjugate

The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU).. We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities.. These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence.

Topics: Adult; Brain; Chronic Disease; Cues; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Rest

This study evaluates whether the instauration of a heroin prescription trial ('NAOMI') generated an impact on the occurrence of crime and disorder in surrounding areas. The clinical trial was initiated in Vancouver and Montreal in 2005, with the aim of assessing the benefits of heroin-assisted treatment (HAT) in Canada. While experiences from other jurisdictions where HAT trials have been implemented clearly demonstrate substantial crime reduction effects for trial participants, there is overall concern that HAT clinics - similar to other interventions aiming at problematic street drug users - may induce a 'honeypot' effect, leading to increases in crime and/or disorder problems in the vicinity of interventions. It has been argued that HAT clinics will attract undesirable behaviour associated with cultures of street drug use and thereby produce negative impacts on the community.. This study examined the incidence of crime and disorder in the Vancouver and Montreal sites before and during the NAOMI trial (2002-2006), using police calls for service and arrest data. Data were analysed by autoregression analyses.. The analysis suggested that most indicators remained stable during the pre- and implementation phase of the NAOMI trial in both sites.. While the attribution of observed crime and disorder trends to the specific clinical interventions in Montreal and Vancouver is difficult and many extrinsic factors may play a role, this study has not generated any clear evidence from institutional police data to suggest increases or decreases in community-based problems associated with HAT programs in Canada.

Topics: British Columbia; Civil Disorders; Clinical Trials as Topic; Community Health Centers; Crime; Heroin; Heroin Dependence; Humans; Narcotics; Quebec; Residence Characteristics; Safety; Statistics as Topic

Switzerland introduced a pragmatic national drug policy when the former conservative abstinence-orientated politics proved unable to cope with an escalating number of users and related negative consequences for public health and public order. The high visibility of 'needle parks' and the size of the acquired immune deficiency disorder (AIDS) epidemic called for a new approach and for national leadership.. To describe the intentions, the process and the results of setting up the new treatment approach of prescribing heroin to treatment resistant heroin addicts, as an example of drug policy change.. A systematic collection of relevant documents is analysed and used as evidence for describing the process of policy change.. Measures to reduce the negative consequences of continued use and to prevent the spread of AIDS were started mainly by private initiatives and soon taken up officially in the 'four-pillar' drug policy (including harm reduction, prevention, treatment and law enforcement). Medical prescription of heroin to chronic, treatment-resistant heroin addicts was one of the innovations, based on extensive scientific and political preparation. Detailed documentation and evaluation, ample communication of results, adaptations made on the basis of results and extensive public debate helped to consolidate the new policy and heroin-assisted treatment, in spite of its limitations as an observational cohort study. All necessary steps were taken to proceed from a scientific experiment to a routine procedure.. Comparable policy changes have been observed in a few other countries, such as The Netherlands and Germany, based on the Swiss experience, with equally positive results of heroin-assisted treatment. These experiments were designed as randomised controlled trials, comparing intravenous heroin against oral methadone, thereby demonstrating the specific value of pharmaceutical diamorphine for maintenance treatment in opiate dependence. The positive impact of policy change and the positive outcomes of heroin-assisted treatment were acknowledged increasingly nationally and internationally, but made it difficult to continue the process of adapting policy to new challenges, due to the low visibility of present drug problems and to changing political priorities.. A major change in drug policy was effectively realised under typical conditions of a federalist country with a longstanding tradition of democratic consensus building. Facilitating factors were the size and visibility of the heroin problem, the rise of the Aids epidemic, and a pragmatic attitude of tolerating private initiatives opening the way to official policy change.

Topics: Cohort Studies; Drug and Narcotic Control; Germany; Harm Reduction; Health Plan Implementation; Heroin; Heroin Dependence; HIV Infections; Humans; Methadone; Narcotics; Needle-Exchange Programs; Netherlands; Political Systems; Program Evaluation; Public Health; Students; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Switzerland; Treatment Outcome

Since the 1980s the abuse of cocaine has been -associated with gastroduodenal perforations in the United States. Here, we report the case of a 28-year-old man who came to our hospital with severe abdominal pain after smoking cocaine. Physical examination revealed generalised abdominal guarding. His X-ray did not show any free intraperitoneal air. However, there was a slightly elevated white blood cell count. Upon laparoscopic exploration of the abdomen, the -patient was found to have a generalised peritonitis secondary to a perforation of the prepyloric anterior wall. The operative procedure consisted of ulcer excision and primary closure with a pyloroplasty as well as an extensive abdominal irrigation after laparotomy.

Topics: Abdomen, Acute; Adult; Cocaine; Cocaine-Related Disorders; Diagnosis, Differential; Heroin; Heroin Dependence; Humans; Laparoscopy; Male; Narcotics; Peptic Ulcer Perforation; Peritonitis; Pylorus; Stomach Ulcer; Vasoconstrictor Agents

We describe a suspicious case involving a previous heroin addict and her newborn child experiencing symptoms suggestive of withdrawal. Therapeutic drug monitoring was used to determine whether in utero exposure took place.

Topics: Diazepam; Drug Monitoring; Female; Heroin; Heroin Dependence; Humans; Hypnotics and Sedatives; Infant, Newborn; Male; Neonatal Abstinence Syndrome; Pregnancy

Topics: Heroin; Heroin Dependence; Humans; Long-Term Care; Narcotics; Treatment Outcome

In 2003, a randomised controlled trial comparing injected diacetylmorphine and oral methadone was carried out in Andalusia, Spain. The subsequent follow-up study evaluated the health and drug use status of participants, 2 years after the completion of the trial.. This follow-up cohort study was carried out between March and August 2006. Data collected included information on socio-demographics, drug use, health and health-related quality of life. We compared data collected before randomisation and at 2 years for the following three groups: those currently on heroin-assisted treatment (C-HAT), those who have discontinued HAT (D-HAT), and those who have never received HAT (N-HAT).. From the total 62 randomised participants in 2003, 54 (87%) were interviewed for this study. Participants were distributed as follow: C-HAT 44.4% (24), N-HAT 22.2% (12) and D-HAT 33.3% (18). Illicit heroin use had a statistically significant decrease in the three groups from baseline to 2 years post trial. Mean days of heroin use were 2.42 (SD = 3.02); 6.56 (SD = 9.48) and 13.92 (SD = 12.59) for the C-HAT, D-HAT and N-HAT groups, respectively. Those currently on HAT were the only group that sustained at 2 years, their marked improvement in health after 9 months of treatment during the trial period.. Patients who received HAT showed better outcomes compared with those not on HAT. The results of this study strengthen the evidence showing that HAT can improve and stabilise the health of long-term heroin users with severe comorbidities and high mortality.

Topics: Adult; Cohort Studies; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Quality of Life; Randomized Controlled Trials as Topic; Spain; Time Factors; Treatment Outcome

Treatment research with opioid-dependent populations has not traditionally distinguished between those dependent on prescription opioids versus dependent upon heroin. Evidence suggests there is a substantial subpopulation of individuals with opioid dependence resulting largely or exclusively from prescription opioid use. Because this subpopulation may respond to treatment differently from heroin users, a method for discriminating DSM-IV opioid dependence due to prescription opioid use would provide more precision when examining this population. This paper describes an innovative method using a currently available diagnostic instrument, to diagnose DSM-IV opioid dependence and distinguish between dependence resulting from prescription opioids versus dependence upon heroin.

Topics: Clinical Trials as Topic; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Heroin; Heroin Dependence; Humans; Prescription Drugs; Psychiatric Status Rating Scales

On March 2007, a police officer (46-year-old man) and a clerk (37-year-old woman) were arrested and subjected to investigation on the charges of drugs of abuse trafficking. The loving couple was exploiting their administrative positions to make money with the resale of seized drugs. The laboratory was requested to analyse their hair for drugs of abuse. Hair of the 2 subjects tested positive for heroin by GC-MS. A few days later, analysis of hair obtained from 11 other police officers of the same unit was requested, in order to compare the results, as external contamination was proposed to account for the positive results. The aim of the investigations was to demonstrate that passive contamination could not occur for persons dealing every day with drugs of abuse with minimal caution and hygiene, and that the measured concentrations in the arrested subjects correspond to personal abuse. All the narcotic team tested negative, irrespective of the compound.

Topics: Adult; Biomarkers; Codeine; Female; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Morphine; Morphine Derivatives; Narcotics; Occupational Exposure; Police

Topics: Animals; Anxiety; Brain; Emotions; Heroin; Heroin Dependence; Humans; Nervous System Diseases; Rats; Stress, Psychological

Topics: Anthrax; Drug Contamination; Germany; Heroin; Heroin Dependence; Humans; Narcotics; United Kingdom

Buprenorphine is a partial opioid agonist with a "ceiling effect" for respiratory depression. Despite this, it has been associated with severe overdoses. Conflicting data exist regarding its response in overdose to naloxone. We compared clinical overdose characteristics of buprenorphine with heroin and methadone and assessed responses to naloxone and flumazenil. Patients admitted to two intensive care units with severe opioid overdoses were enrolled into this 4-year prospective study. Urine and blood toxicological screening were performed to identify overdoses involving predominantly buprenorphine, heroin, or methadone. Eighty-four patients with heroin (n = 26), buprenorphine (n = 39), or methadone (n = 19) overdoses were analyzed. In the buprenorphine group, sedative drug coingestions were frequent (95%), whereas in the methadone group, suicide attempts were significantly more often reported (p = .0007). Buprenorphine overdose induced an opioid syndrome not differing significantly from heroin and methadone in mental status (as measured by Glasgow Coma Score) or arterial blood gases. Mental status depression was not reversed in buprenorphine overdoses with naloxone (0.4-0.8 mg) but did improve with flumazenil (0.2-1 mg) if benzodiazepines were coingested. In conclusion, buprenorphine overdose causes an opioid syndrome clinically indistinguishable from heroin and methadone. Although mental status and respiratory depression are often unresponsive to low-dose naloxone, flumazenil may be effective in buprenorphine overdoses involving benzodiazepines.

Topics: Adult; Antidotes; Buprenorphine; Drug Overdose; Female; Flumazenil; Heroin; Heroin Dependence; Humans; Intensive Care Units; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Prospective Studies; Suicide, Attempted

To evaluate the influence of an initial heroin experience under a modified two-chained training schedule on drug-seeking behavior after a long abstinence period.. Rats were trained to respond for intravenous heroin (120 microg/kg) under a heterogeneous chained schedule of reinforcement using different responses in the first and second links of the chain. Animals received low-frequency drug administration training for four days and were then subjected to one month of abstinence in their home cages. Heroin-seeking behavior induced by re-exposure to the first chain associated context or discriminative stimuli was assessed after abstinence.. Almost all animals could acquire operant skills quickly under the two-chained schedule training for four days, as measured in first active response latency, travel speed and goal-box enter latency. Both first chain associated context and discriminative stimulus could reinstate heroin-seeking behavior after one month abstinence.. These observations suggest that an early experience of drug use is sufficient to maintain heroin-seeking behavior even after a one month abstinence.

Topics: Animals; Behavior, Animal; Conditioning, Operant; Heroin; Heroin Dependence; Male; Narcotics; Rats; Rats, Sprague-Dawley

Toxic leukoencephalopathy has been associated with illicit heroin vapor inhalation. Despite the nonspecific and variable clinical presentation of these patients, they show typical radiologic findings. Previous studies evaluated typical radiologic findings with symmetric infratentorial hyperintense signal changes and similar alteration in the posterior limb of the internal capsule, the splenium of corpus callosum, the medial lemniscus and the lateral brainstem. In context with the reviewed literature, a series of another three cases with toxic leukoencephalopathy after heroin abuse other than vapor inhalation is presented.. All three patients underwent magnet resonance imaging (MRI) including additional diffusion- weighted imaging and apparent diffusion coefficient maps. Clinical and laboratory findings were recorded.. MRI of all three patients revealed similar symmetric supratentorial hyperintense signal changes involving the frontal, parietal, occipital and temporal lobes. The cortex was spared and the subcortical U fibers were partially involved. Further, the brainstem and the cerebellar white matter were not affected.. Toxic leukoencephalopathy without involvement of the cerebellum and brainstem is a rare complication of heroin abuse. The pattern of heroin-induced toxic leukoencephalopathy on MRI might not only be related to an unknown adulterant, but also to the mode of drug administration.

Topics: Administration, Inhalation; Adult; Brain Stem; Cerebellar Diseases; Diffusion Tensor Imaging; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Male

CD56(+) T cells are abundant in liver and play an important role in host innate immunity against viral infections, including hepatitis C virus (HCV) infection, a common infection among heroin abusers. We thus investigated the in vivo impact of heroin use or heroin use plus HCV infection on the CD56(+) T cell frequency and function.. A total of 37 heroin users with (17) or without (20) HCV infection and 17 healthy subjects were included in the study. Although there was no significant difference in CD56(+) T cell frequency in PBMCs among three study groups, CD56(+) T cells isolated from the heroin users had significantly lower levels of constitutive interferon-gamma (IFN-gamma) expression than those from the normal subjects. In addition, when stimulated by interleukin (IL)-12, CD56(+) natural T cells from HCV-infected heroin users produced significantly lower levels of IFN-gamma than those from the normal subjects. This diminished ability to produce IFN-gamma by CD56(+) T cells was associated with the increased plasma HCV viral loads in the HCV-infected heroin users. Investigation of the mechanisms showed that although heroin use or heroin use plus HCV infection had little impact on the expression of the key positive regulators (IL-12 receptors, STAT-1, 3, 4, 5, JAK-2, and TYK-2) in IL-12 pathway, heroin use or heroin use plus HCV infection induced the expression of suppressor of cytokine signaling protein-3 (SOCS-3) and protein inhibitors of activated STAT-3 (PIAS-3), two key inhibitors of IL-12 pathway.. These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56(+) T cell-mediated innate immune function, which may account for HCV infection and persistence in liver.

Topics: CD56 Antigen; Gene Expression Regulation, Viral; Hepacivirus; Hepatitis C; Heroin; Heroin Dependence; Humans; Interferon-gamma; Interleukin-12; Leukocytes, Mononuclear; Liver; Molecular Chaperones; Protein Inhibitors of Activated STAT; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; T-Lymphocytes; Up-Regulation

To elucidate the relation between cytochrome P4502D6 (CYP2D6) gene polymorphism and the susceptibility of heroin spongiform leucoencephalopathy (HSLE).. With polymerase chain reaction-restriction fragment length polymorphism technique, the cytochrome P4502D6 gene polymorphisms were analyzed in HSLE cases and control subjects.. The frequencies of CYP2D6 (CYP2D6/C188, CYP2D6/L2938, CYP2D6/G4268) gene mutations were higher in HSLE patients than in the controls.. The CYP2D6 gene mutation is associated with a high risk of HSLE.

Topics: Adult; Canavan Disease; Cytochrome P-450 CYP2D6; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Mutation; Polymorphism, Restriction Fragment Length; Young Adult

The dominant Australian approaches to understanding illicit drug marketplaces are surveillance and criminological research. These approaches rely on the elementary neoclassical economic model of the market which focuses primarily on supply and demand. In this paper, we draw on anthropological and sociological research to develop an alternative framework for understanding Australian illicit drug marketplaces that emphasises their constituent processes.. The paper draws on two years of ethnographic research among heroin user/sellers of Vietnamese ethnicity in an Australian heroin marketplace.. Trade and barter were key modes of exchange in this marketplace. We identified active negotiation and bargaining over price on the basis of social relationships, with dealers and customers actively working to develop and maintain such ties. Dealers set price collectively and this was shaped by moral and cultural elements such as notions of a 'fair' price. Social processes and relations as well as shared cultural expectations helped to generate trust and maintain order in the marketplace.. Our ethnographic research suggests that the dominant Australian approaches to the study of illicit drug markets, with their reliance on the elementary neoclassical economic market model, ignore the social processes and social relations through which such sites are made and remade. Nor do they adequately capture the complex character of the subjects who act within these sites. If we are to expand our understanding of illicit drug markets and marketplaces in Australia, we must look beyond the conceptions offered by surveillance and criminological approaches.

Topics: Adolescent; Adult; Anthropology, Cultural; Australia; Commerce; Cultural Evolution; Drug and Narcotic Control; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Income; Male; Social Environment; Substance Abuse, Intravenous; Vietnam; Young Adult

This monograph describes the history, findings and international context of heroin-assisted treatment (HAT) in the Netherlands. The monograph consists of (1) a short introduction and seven paragraphs describing the following aspects of HAT in the Netherlands: (2) history of HAT studies and implementation of routine HAT in the Netherlands; (3) main findings on efficacy, safety and cost-effectiveness from the two randomized controlled HAT trials in the Netherlands; (4) new findings from a large cohort study on the effectiveness of HAT in routine clinical practice in the Netherlands; (5) unique data on the patient's perspective of HAT; (6) data on the pharmacological and pharmaceutical basis for HAT in the Netherlands; (7) description of the registration process; and (8) account of the international context of HAT. Together, these data show that HAT can now be considered a safe and proven-effective intervention for the treatment of chronic, treatment-resistant heroin dependent patients.

Topics: Adult; Cost-Benefit Analysis; Drug Prescriptions; Female; Heroin; Heroin Dependence; History, 20th Century; History, 21st Century; Humans; Male; Narcotics; Netherlands; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

An accidental death caused by the combined use of a new designer drug, 4-methylmethcathinone (mephedrone), and heroin is reported. A 22-year-old Caucasian male was found unresponsive in his living quarters and was transported to the hospital where he died. During autopsy, needle marks were found along the decedent's lower legs and ankles. Investigators discovered the decedent and his roommate had been using "Black Tar" heroin and mephedrone. Routine toxicological analysis detected morphine in the decedent's blood at 0.06 mg/L. Additionally, 6-acetylmorphine, morphine, codeine, and doxylamine were detected in his urine. A designer drug screen, employing a basic liquid-liquid extraction followed by pentafluropropionic anhydride derivatization, was used to isolate mephedrone from both blood and urine specimens. The derivatized extracts were analyzed by gas chromatography- mass spectrometry (GC-MS) operating in full-scan mode. Quantitative analysis of mephedrone was performed by GC-MS operating in selective ion monitoring mode using methamphetamine-d(14) as an internal standard. Mephedrone was confirmed in the decedent's blood and urine at 0.50 and 198 mg/L, respectively. The physiological and pharmacological effects of mephedrone and any associated toxicity have not been reported. However, because of its structural similarities with methcathinone and the high concentration in the decedent's blood, the overall contribution of mephedrone to the death could not be minimized. Therefore, the medical examiner reported the cause of death as multiple-drug toxicity and the manner of death as accidental.

Topics: Amphetamine-Related Disorders; Chromatography, Gas; Codeine; Doxylamine; Drug Overdose; Fatal Outcome; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Immunoassay; Male; Methamphetamine; Morphine; Morphine Derivatives; Reproducibility of Results; Substance Abuse Detection; Young Adult

This article aims at exploiting the statistical data of the qualitative and quantitative analyses of heroin circulating in France over more than 20 years. This information, systematically recorded by the Forensic Laboratories from Institut national de police scientifique is a good source of knowledge of this product at both the chemical and sanitary levels (street level, wholesalers, imports, etc.).

Topics: Crime; Databases, Factual; Forensic Toxicology; France; Heroin; Heroin Dependence; Humans; Laboratories; Law Enforcement

The fact that particular parents suffer afflictions limiting their ability to care does not mean that they should automatically be deemed unsuitable parents. Prompted by neonatal team concerns about child-care issues, a local multidisciplinary group was set up to care for substance-abusing pregnant women in our region.. This project was conducted in order to review the records of all the women who had been discussed at our management planning meetings over the past 5 years. Our assessment tool records were reviewed and analysed using spss.. A total of 233 women were assessed. The majority of patients booked before 20 weeks (62%) and 96 women (41%) attended over 80% of their antenatal appointments. There was little change in substance use during the course of pregnancy. Overall, at delivery, 196 of the 233 women (84%) used methadone and 89(38%) used heroin. There was no correlation between usage and foster care of the baby (methadone: chi(2) = 0.5, P = 0.8 NS) (heroin: chi(2) = 3.1, P = 0.08 NS). There was an absolute correlation between social services involvement and foster care (chi(2) = 2.33, P < 0.0001). Adherence with planned antenatal appointments significantly increased the likelihood of a child being discharged with his mother (chi(2) = 6.7, P = 0.009).. The majority of newborns were discharged home with their mothers directly with the most significant factor in placing a child in foster care being prior involvement of social services. However, many of these families will continue to need support during the children's early years.

Topics: Appointments and Schedules; Female; Foster Home Care; Heroin; Heroin Dependence; Humans; Infant, Newborn; Methadone; Opioid-Related Disorders; Patient Compliance; Pregnancy; Pregnancy Complications; Prenatal Care; Social Work

Topics: Administration, Oral; Heroin; Heroin Dependence; Humans; Injections; Methadone; Narcotics; Politics; Prescription Drugs

Topics: Adult; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Narcotics

Opiate abuse has been linked to oxidative stress, through the separate evaluation of oxidants and antioxidants.. To determine prooxidant-antioxidant balance (PAB) in chronic heroin users in a single assay, easily applied in a clinical setting. Specifically, to examine whether PAB values correlate with the duration of abuse or with the presence of anti-HCV antibodies.. Sixty-four chronic heroin users - 34 cases and 30 controls - participated in this study. PAB was determined by an Enzyme-linked immunosorbent assay (ELISA) method, developed by members of the study group.. In heroin users, oxidative balance was disrupted in favor of prooxidants. There was no correlation of PAB values with the duration of abuse or with the presence of anti-Hepatitis C virus (HCV) antibodies.. Chronic heroin users can benefit from an antioxidant therapy, and the method currently presented can be used as an identification criterion.

Topics: Adult; Analgesics, Opioid; Antioxidants; Case-Control Studies; Greece; Hepatitis C Antibodies; Heroin; Heroin Dependence; Humans; Male; Oxidants; Oxidative Stress; Young Adult

To evaluate the effect of methadone maintenance treatment (MMT) on cocaine use and cocaine injection among heroin users.. Generalized estimating equations (GEE) were used to examine the association between MMT enrollment (0, <12, ≥12 months) and changes in frequency of cocaine use or injection in two consecutive follow-up visits among heroin users in the Itinere cohort, and to determine whether these changes were independent of equivalent changes in heroin use or injection. Seven multivariate models were constructed, one for each outcome variable on drug use changes.. Of the 992 participants recruited in 2001-2003, 628 (63.3%) had at least one follow-up visit. Of these, 55.8% were enrolled in MMT at baseline and an additional 23.2% initiated MMT during follow-up. In multivariate GEE, changes significantly and positively associated with MMT enrollment were: less cocaine use [MMT<12 months (OR=1.70, 95% CI=1.17-2.48)] and less cocaine injection [MMT≥12 months (OR=2.98, 95% CI=1.51-5.89)]. Being on MMT≥12 months was negatively associated with more cocaine use (OR=0.62, 95% CI=0.38-0.99) and with more cocaine injection (OR=0.52, 95% CI=0.28-0.98). When equivalent changes in heroin were used as a covariate, the MMT effect on less cocaine use was hardly modified (OR=1.69, 95% CI=1.07-2.65), and the effect on changes in cocaine injection disappeared.. MMT enrollment is a protective factor against both cocaine use and injection among heroin users. The effect of MMT on cocaine injection appears to be mediated by heroin injection, whereas its effect on cocaine use is more direct.

Topics: Cocaine; Cocaine-Related Disorders; Cohort Studies; Female; Heroin; Heroin Dependence; Humans; Injections; Male; Methadone; Narcotics; Opiate Substitution Treatment; Substance Abuse, Intravenous

Successful treatment of drug addiction is hampered by high relapse rates during periods of abstinence. Neuroadaptation in the medial prefrontal cortex (mPFC) is thought to have a crucial role in vulnerability to relapse to drug seeking, but the molecular and cellular mechanisms remain largely unknown. To identify protein changes that contribute to relapse susceptibility, we investigated synaptic membrane fractions from the mPFC of rats that underwent 21 days of forced abstinence following heroin self-administration. Quantitative proteomics revealed that long-term abstinence from heroin self-administration was associated with reduced levels of extracellular matrix (ECM) proteins. After extinction of heroin self-administration, downregulation of ECM proteins was also present in the mPFC, as well as nucleus accumbens (NAc), and these adaptations were partially restored following cue-induced reinstatement of heroin seeking. In the mPFC, these ECM proteins are condensed in the perineuronal nets that exclusively surround GABAergic interneurons, indicating that ECM adaptation might alter the activity of GABAergic interneurons. In support of this, we observed an increase in the inhibitory GABAergic synaptic inputs received by the mPFC pyramidal cells after the re-exposure to heroin-conditioned cues. Recovering levels of ECM constituents by metalloproteinase inhibitor treatment (FN-439; i.c.v.) prior to a reinstatement test attenuated subsequent heroin seeking, suggesting that the reduced synaptic ECM levels during heroin abstinence enhanced sensitivity to respond to heroin-conditioned cues. We provide evidence for a novel neuroadaptive mechanism, in which heroin self-administration-induced adaptation of the ECM increased relapse vulnerability, potentially by augmenting the responsivity of mPFC GABAergic interneurons to heroin-associated stimuli.

Topics: Animals; Chromatography, High Pressure Liquid; Conditioning, Operant; Cues; Drug Administration Schedule; Enzyme Inhibitors; Extracellular Matrix; gamma-Aminobutyric Acid; Gene Expression Regulation, Enzymologic; Heroin; Heroin Dependence; Hydroxamic Acids; In Vitro Techniques; Male; Mass Spectrometry; Narcotics; Oligopeptides; Prefrontal Cortex; Proteomics; Pyramidal Cells; Rats; Rats, Wistar; Reinforcement Schedule; Self Administration; Signal Transduction; Synaptic Potentials

A key aim of supply-side drug law enforcement is to reduce drug use by increasing the retail price of drugs. Since most illicit drug users are polydrug users the effectiveness of this strategy depends on the extent to which drug users reduce their overall consumption of drugs. The literature shows that drug users do reduce their consumption of a drug when its price increases. However the extent of that decrease and the implications for the use of other drugs vary across studies.. A sample of 101 Australian methamphetamine users was surveyed using a behavioural economics approach. Participants were given a hypothetical fixed drug budget, presented with a range of drug price lists and asked how many units of each drug they would purchase. Methamphetamine and heroin prices were varied independently across trials.. While demand for both methamphetamine and heroin was found to be price elastic, elasticity estimates were influenced by the nature of participants' drug dependence. The group least responsive to changes in methamphetamine price were those dependent only on methamphetamine, while the group most responsive were dependent only on heroin. Similar findings emerged in relation to changes in heroin price. Cross-price elasticity analysis showed limited substitution into other drugs as the price of methamphetamine increased. In contrast, for heroin, there was significant substitution into pharmaceutical opioids and to a lesser extent, benzodiazepines and methamphetamine. However, for the most part, the decreases in methamphetamine or heroin consumption outweighed any substitution into other drugs.. The reduction in overall drug consumption and expenditure in response to price increases in heroin and methamphetamine observed in this sample lend support to supply-side enforcement strategies that aim to increase retail drug price. Notably, this analysis highlights the importance of accounting for the nature of users' drug dependence in estimating price responsiveness.

Topics: Adolescent; Adult; Amphetamine-Related Disorders; Australia; Commerce; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Law Enforcement; Male; Mental Health Services; Methamphetamine; Middle Aged; Substance Abuse, Intravenous; Substance-Related Disorders; Surveys and Questionnaires; Young Adult

Heroin use is associated with many serious consequences.While effective treatments exist, barriers to services persist. Understanding service use and barriers to treatment can structure treatment practice and target interventions for those who are most at risk.. To describe patterns and correlates of substance abuse service utilization and treatment barriers among a nationally representative sample of heroin users.. Data for this study were derived from the National Epidemiologic Survey on Alcohol and Related Conditions. This study focused on lifetime heroin users (N = 150).. Fifty-nine percent of heroin users reported receiving at least one treatment service. The most common services used were 12-step programs, detoxification, and rehabilitation. Approximately 44% reported at least one barrier to treatment. The most common were lack of motivation and beliefs that it could be managed alone. In a multivariate logistic regression, having a heroin use disorder was associated with a greater likelihood of receiving services (OR = 6.09) and experiencing a barrier (OR = 11.11) compared to those without a disorder.. High rates of service use and barriers were observed for all levels of heroin involvement. These findings underscore the importance of improving access to services for this group, even when full criteria for a drug disorder is not met. Integration of motivational approaches is also needed within the most common services used. To our knowledge, this is the first study to describe patterns and correlates of service use using a nationally representative community sample of heroin users.

Topics: Adult; Data Collection; Female; Health Services Accessibility; Healthcare Disparities; Heroin; Heroin Dependence; Humans; Male; Mental Health Services; Middle Aged; Substance Abuse Treatment Centers; United States

The neural and psychological mechanisms underlying vulnerability to drug addiction are poorly understood. Although a number of animal models have been developed to investigate vulnerability to stimulant addiction, few have considered how vulnerability traits such as impulsivity predict hallmark features of heroin addiction including the escalation of drug intake and increased propensity for relapse following protracted abstinence.. The aim of this study was to investigate whether high impulsivity in rats predicts the propensity to escalate intravenous heroin self-administration and to relapse following an extended withdrawal period from heroin.. High (HI)- and low (LI)-impulsive rats, defined by the extent of premature responding on the 5-choice serial reaction time test (5-CSRTT), were catheterized and allowed to self-administer heroin (40 μg/100 μl/infusion). After 5 days of short access (1 h/day) to heroin, rats were then given extended (6 h/day) access to heroin for 18 consecutive days.. High impulsivity predicted neither a greater tendency to acquire heroin SA nor an increased escalation of heroin self-administration. Moreover, high impulsivity was not associated with an increased propensity to relapse after protracted withdrawal from heroin. Nevertheless, marked inter-individual differences in the escalation of heroin self-administration were observed.. Although high impulsivity on the 5-CSRTT has been shown to predict loss of control over cocaine intake, this does not generalize to a loss of control over heroin self-administration. These findings suggest important distinctions in vulnerability mechanisms underlying cocaine and heroin addiction with trait-like impulsivity playing a role in stimulant but not opiate addiction.

Topics: Analgesics, Opioid; Animals; Attention; Behavior, Addictive; Behavior, Animal; Conditioning, Operant; Cues; Extinction, Psychological; Heroin; Heroin Dependence; Infusions, Intravenous; Male; Rats; Recurrence; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome; Time Factors

To evaluate the effects of washing process on hair samples from heroin addicts, and compare the extracting method of enzymatic digestion with homogenization of hair samples.. After washing samples for 3.15 h, a mild enzymatic digestion procedure at pH 6.6 and a buffer incubating procedure in water bath at 48 degrees C during 18h was used. The samples were pre-treated by solid phase extraction using mixed mode sorbent columns (MCX Oasis). Quantitative analysis of morphine, codeine, 6-acetylmorphine, heroin, acetylcodeine by chromatography-tandem mass spectrometry method was developed.. Heroin accounted for 21.82% of the total equivalents of morphine. The ratio of morphine to 6-MAM in enzymatic digestion hair samples was 0.9875 and that in homogenized hair samples was 0.3948.. The results suggested that the procedures were not sufficient to remove the contaminants penetrating into hair from external sources.

Topics: Chromatography, Liquid; Codeine; Hair; Heroin; Heroin Dependence; Humans; Morphine; Morphine Derivatives; Solid Phase Extraction; Tandem Mass Spectrometry

Childhood trauma has been reported as a possible cause of future substance abuse in some countries. This study reports the prevalence of childhood trauma and examines its association with psychological distress among injecting drug users from mainland China.. The study was conducted in three government-operated drug rehabilitation facilities in Shanghai, China in 2007. The Early Trauma Inventory Self Report-Short Form (ETISR-SF) was used to evaluate 4 types (general, emotional, physical and sexual) and severity of childhood trauma, and the Symptom Checklist-90-Revised (SCL-90-R) to evaluate psychological distress.. Among 341 injecting drug users who completed the study, about 80% reported one or more types of childhood trauma, specifically 53% general trauma, 56% physical abuse, 36% emotional abuse and 26% sexual abuse. Compared to female injecting drug users, males reported significantly higher scores of general trauma and physical abuse, but lower sexual abuse scores. Hierarchical linear regression analyses showed that greater physical and emotional abuse in childhood predict greater current psychopathological distress among these injecting drug users in China.. The results reveal a high prevalence of childhood trauma among injecting drug users in China, and it is comparable to other similar studies in Western countries. It is important to consider the role of childhood trauma in the prevention and treatment of substance abuse.

Topics: Adult; Child; Child Abuse; China; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Prevalence; Regression Analysis; Stress Disorders, Traumatic; Substance Abuse, Intravenous

Before implementing the TADAM project in Belgium (a heroin-assisted treatment trial), our research team studied the trials in other countries. Since 1994, six randomised controlled trials have been developed using the same treatment model of heroin-assisted treatment (HAT). Each trial concluded that HAT had more efficacy than methadone treatment. We analysed those trials in order to find on which levels patients in a HAT treatment are expected to improve. Improvements appeared after at least six months on the level of street heroin use, (physical and mental) health and criminal behaviour. In the longer term, the continuation of treatment had positive but limited effects on the social level. Due to his higher cost, this treatment should remain a second-line treatment for this special target group: severe heroin addicts, using continuously street heroin in spite of a methadone treatment.

Topics: Heroin; Heroin Dependence; Humans; Narcotics; Opiate Substitution Treatment; Randomized Controlled Trials as Topic

Opiate addiction has been widely documented to have negative impact on pregnancy course and outcome. Unfavorable psychosocial situation of addicted women predispose for poor processing of the physiological and psychological demands of pregnancy. Thus aim of our study was to investigate the psychological mood state of opiate addicts during pregnancy and postpartum in comparison to healthy women. In a case-controlled, prospective, longitudinal study nine pregnant opiate addicts and nine healthy pregnant women matched by age, level of education and gestational age at birth were interviewed in the third trimester of pregnancy and postpartum. Standardized questionnaires and inventories for assessment of the general psychopathology and emotional state, the perceived self-efficacy expectancy, the psychosocial adaptation to pregnancy and the fear of delivery, respectively were applied. Addicted women achieved significantly higher scores in the test assessing general psychopathology and emotional state before delivery compared to abstinent women. Interestingly this difference was unverifiable postpartum. This study reaffirms the presumption of a disadvantageous psychological condition in pregnant opiate addicts in comparison to healthy pregnant women for the first time in a prospective case-control study design.

Topics: Adult; Affect; Anxiety; Case-Control Studies; Cocaine; Cocaine-Related Disorders; Comorbidity; Depression, Postpartum; Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Longitudinal Studies; Narcotics; Parturition; Personality Inventory; Pregnancy; Pregnancy Complications; Prospective Studies; Psychometrics; Self Efficacy; Social Support; Young Adult

One month before (T-1) and 12 months after (T12) controlled i.v. administration of pharmaceutical heroin-HCl (10-100 mg/day) in the context of a heroin maintenance program (HMP), concentrations of opiates and cocaine as well as its metabolites were determined in head hair (n = 46) using a validated gas chromatographic-mass spectrometric method. In addition, a patient collective of a methadone maintenance program (MMP, daily doses 15-260 mg) was examined (n = 35). The incidence of additional cocaine consumption decreased in both groups during the study period (T-1 to T12): in HMP from 64.6% to 45.8% and in MMP from 71.4% to 60.0%. A significant reduction of cocaine consumption was defined as an at least 30% reduction of analyte concentrations in hair (Deltac > 30%). Accordingly, in HMP, a decrease in 45.8% of initially (T-1) cocaine-positive patients was determined; in MMP, the reduction was 48.6%. In 22.9% of HMP and 37.1% of MMP, an increase of cocaine concentrations was detected. Codeine and acetylcodeine were found in 50.0% and 43.5% (T-1) and 13.0% and 10.9% (T12) of the samples of the HMP, as well as in 45.7% and 25.7% (T-1) and 17.1% and 5.7% (T12) in MMP, respectively. The missing of acetylcodeine, in particular at T-1, questions its applicability as a characteristic marker of a preceding consumption of illicit heroin in hair analysis.

Topics: Cocaine; Codeine; Dopamine Uptake Inhibitors; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Heroin Dependence; Humans; Linear Models; Methadone; Narcotics; Substance Abuse Detection

Previous studies have reported that noradrenergic antagonists alleviate some of the symptoms of opiate withdrawal and dependence. Clinical studies also have shown that modification of the noradrenergic system may help protect patients from relapse. The present study tested the hypothesis that a dysregulated noradrenergic system has motivational significance in heroin self-administration of dependent rats. Prazosin, an alpha1-adrenergic antagonist (0.5, 1.0, 1.5 and 2.0 mg/kg, i.p.), was administered to adult male Wistar rats with a history of limited (1 h/day; short access) or extended (12 h/day; long access) access to intravenous heroin self-administration. Prazosin dose-dependently reduced heroin self-administration in long-access rats but not short-access rats, with 2 mg/kg of systemic prazosin significantly decreasing 1 h and 2 h heroin intake. Prazosin also reversed some changes in meal pattern associated with extended heroin access, including the taking of smaller and briefer meals (at 3 h), while also increasing total food intake and slowing the eating rate within meals (both 3 h and 12 h). Thus, prazosin appears to stimulate food intake in extended access rats by restoring meals to the normal size and duration. The data suggest that the alpha1 adrenergic system may contribute to mechanisms that promote dependence in rats with extended access.

Topics: Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Antagonists; Animals; Conditioning, Operant; Dose-Response Relationship, Drug; Drinking; Eating; Heroin; Heroin Dependence; Male; Narcotics; Prazosin; Rats; Rats, Wistar; Reinforcement Schedule; Self Administration; Substance Abuse, Intravenous

Opioid withdrawal can produce a constellation of physiological and behavioral signs, including an increase in opioid self-administration. Different mechanisms mediate different withdrawal signs, and the present study used pharmacologic tools to assess mechanisms underlying withdrawal-associated increases in opioid reinforcement. Five rhesus monkeys were rendered heroin dependent via daily 21-h heroin self-administration sessions. One hour after each heroin self-administration session, monkeys chose between heroin (0-0.1 mg/kg per injection) and food (1 g pellets) during 2-h choice sessions. Under these conditions, heroin maintained a dose-dependent increase in heroin choice, such that monkeys responded primarily for food when low heroin doses were available (0-0.01 mg/kg per injection) and primarily for heroin when higher heroin doses were available (0.032-0.1 mg/kg per injection). Periods of spontaneous withdrawal were intermittently introduced by omitting one 21-h heroin self-administration session, and test drugs were administered during these withdrawal periods. Untreated withdrawal robustly increased heroin choice during choice sessions. Withdrawal-associated increases in heroin choice were completely suppressed by the mu opioid agonist morphine (0.032-0.32 mg/kg/h, i.v.), but not by the alpha-2 noradrenergic agonist clonidine (0.01-0.1 mg/kg/h, i.v.), the dopamine/norepinephrine releaser amphetamine (0.032-0.1 mg/kg/h, i.v.), or the kappa-opioid antagonist 5'-guanidinonaltrindole (1.0 mg/kg, i.m.). The corticotropin-releasing factor 1 antagonist antalarmin (1.0-10 mg/kg per day, i.m.) produced a morphine-like suppression of withdrawal-associated increases in heroin choice in one of three monkeys. These results suggest that mechanisms of withdrawal-associated increases in the relative reinforcing efficacy of opioid agonists may be different from mechanisms of many other somatic, mood-related, and motivational signs of opioid withdrawal.

Topics: Adrenergic Agents; Adrenergic Agonists; Amphetamine; Animals; Behavior, Addictive; Choice Behavior; Clonidine; Dopamine Agents; Dose-Response Relationship, Drug; Food; Heroin; Heroin Dependence; Macaca mulatta; Male; Morphine; Narcotic Antagonists; Pyrimidines; Pyrroles; Receptors, Corticotropin-Releasing Hormone; Self Administration; Substance Withdrawal Syndrome

Mu opioid receptors (MOP-r) play an important role in the rewarding and locomotor stimulatory effects of heroin. The aim of the current study was to determine whether infusion of small interfering RNAs (siRNA) targeting MOP-r into the midbrain could knock down MOP-r mRNA and affect heroin-induced locomotor activity or heroin-induced conditioned place preference. Ten-week-old male C57BL/6J mice were surgically implanted bilaterally with guide cannulae directed between the substantia nigra and ventral tegmental area. After 4 days' recovery, mice were infused bilaterally with siRNAs that target the MOP-r (2 mMx0.75 microl/side/day for 3 days) or control siRNA. Seven days after the last infusion, a procedure for conditioned place preference was begun with four heroin (3 mg/kg i.p.) administration sessions alternating with four saline sessions. While heroin induced an increase in locomotor activity in all groups, siRNAs targeting specific regions of MOP-r significantly attenuated this effect. Of particular interest, mice infused with specific siRNAs targeting the MOP-r failed to develop and express conditioned place preference to heroin, or showed a significantly attenuated preference. These alterations in reward-related behaviors are likely due to the reduction in MOP-r mRNA and protein, shown in separate studies by in situ hybridization and autoradiography using the same MOP-r- siRNA infusions. Taken together, these studies demonstrate the utility of siRNA in the neurobiological study of specific components of the reward system and should contribute to the study of other complex behaviors.

Topics: Analysis of Variance; Animals; Autoradiography; Heroin; Heroin Dependence; Locomotion; Male; Mice; Mice, Inbred C57BL; Reaction Time; Receptors, Opioid, mu; Reward; RNA, Small Interfering; Substantia Nigra; Time Factors; Ventral Tegmental Area

Heroin coming into the United States historically comes from three widely dispersed geographical regions: Southwest Asia, Southeast Asia and Mexico. A fourth source of US-bound heroin, from Colombia, originated in the early 1990s. The fact that the four heroin sources produce differing morphologies and qualities of heroin has not been critically examined. In addition, it is not well established how the contemporary competing dynamics of interdiction, or restriction of heroin flows across international boundaries, and neoliberal, e.g., global expansion of free trade, policies are affecting heroin markets. This paper will highlight changes in the US heroin market, including source trends, the political economy of the now dominant source and the resultant effects on the heroin risk environment by US region.. Using a structural and historical framework this paper examines two decades of secondary data sources, including government and drug control agency documents, on heroin flows together with published work on the political and economic dynamics in Latin America.. Co-occurring neoliberal economic reforms may have contributed to paradoxical effects of US/Colombian interdiction efforts. Since entering the US market, heroin from Colombia has been distributed at a much higher quality and lower retail price. An increasingly exclusive market has developed with Mexican and Colombian heroin gaining market share and displacing Asian heroin. These trends have had dramatic effects on the risk environment for heroin consumers. An intriguing factor is that different global sources of heroin produce substantially different products. Plausible associations exist between heroin source/form and drug use behaviours and harms. For example, cold water-soluble powdered heroin (sources: Asia, Colombia) may be associated with higher HIV prevalence in the US, while low-solubility "black tar" heroin (BTH; source: Mexico) is historically used in areas with reduced HIV prevalence. BTH is associated with soft tissue infections caused by Clostridium bacteria.. Source and type of heroin are structural factors in the risk environment of heroin users: source dictates distribution and type predicts practice. How specific types of heroin are used and with what risk is therefore distributed geographically. Continued flux in the heroin market and its effects on the risk environment for drug users deserves further attention.

Topics: Clostridium Infections; Commerce; Crime; Drug and Narcotic Control; Heroin; Heroin Dependence; History, 20th Century; History, 21st Century; HIV Infections; Humans; Illicit Drugs; Politics; Public Policy; Risk; Risk-Taking; United States

Environmental conditions during adolescence, a critical period of brain maturation, can have important consequences on subsequent vulnerability to drugs of abuse. We have recently found that the behavioral effects of cocaine as well as its ability to increase expression of zif-268 are reduced in mice reared in enriched environments (EE).. The present experiments examined whether environmental enrichment has protective influences on the effects of heroin, a drug of addiction whose mechanism of action differs from that of cocaine.. Mice were housed either in standard environments (SE) or in EE from weaning to adulthood before any drug exposure. EE were constituted by big housing cages and contained constantly a running wheel and a small house and four to five toys that were changed once a week with new toys of different shapes and colors. We assessed the influence of EE on the ability of heroin to (1) induce conditioned place preferences, (2) induce behavioral sensitization, (3) increase dopamine levels in the nucleus accumbens (NAc), and (4) increase expression of the immediate early gene zif-268 in the striatum.. Conditioned place preference but not behavioral sensitization was reduced in EE mice compared to SE mice. Heroin induced similar increases in dopamine levels and in the expression of zif-268 in the NAc of EE and SE mice.. The rewarding effects of heroin are blunted by EE and appear to be, at least in part, independent from activation of the mesolimbic system.

Topics: Animals; Behavior, Animal; Conditioning, Psychological; Environment; Heroin; Heroin Dependence; Male; Mice; Mice, Inbred C57BL; Reward

Topics: Adult; Analgesics, Opioid; Aorta; Blood Pressure; Buprenorphine; Female; Hemodynamics; Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

A high incidence of relapse can be triggered by exposure to conditioned cues previously associated with heroin. Extended access to drug and withdrawal are thought to affect the motivation for drug seeking.. The present study evaluated how different periods of training to self-administer heroin and different periods of withdrawal affected drug seeking.. Following 1 to 14 days of heroin self-administration, rats were left in the home environment for 1 or 14 days. Subsequently, rats were evaluated for extinction of nose poke during the first hour after being returned to the training apparatus. One hour later, a conditioned stimulus was presented to initiate cue-induced reinstatement.. Extending the training period from 1 to 14 days caused an escalation of reinstatement of drug seeking induced by conditioned cues. Increasing the withdrawal period from 1 to 14 days produced a similar increase in reinstatement of drug seeking induced by cues. Reinstatement of drug seeking induced by cues was augmented by pretreatment with naltrexone (1, 5 mg/kg) 24 h prior to reinstatement on day 1, but not at 14 days of withdrawal from heroin self-administration.. These experiments demonstrate that increasing the duration of either heroin self-administration or the withdrawal periods from heroin self-administration augments the reinstatement induced by cues that were associated previously with heroin reinforcement. Additionally, we provide one of the first demonstrations that opiate withdrawal induces heroin seeking, as assessed in the reinstatement model.

Topics: Animals; Behavior, Addictive; Behavior, Animal; Conditioning, Operant; Cues; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Exploratory Behavior; Heroin; Heroin Dependence; Male; Naltrexone; Narcotic Antagonists; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Secondary Prevention; Self Administration; Substance Withdrawal Syndrome

There is limited published data to aid interpretation of analytical findings from hair analysis. The aim of the study was to collate 6-monoacetylmorphine (6-AM) and morphine concentrations in head and pubic hair from heroin users and to propose reference ranges and relate these to the amount of heroin used. The ratio of morphine-to-6-AM was also investigated. A total of 82 head hair samples divided into 173 segments of various lengths and 15 pubic hair samples were collected at postmortem from heroin users. The hair was analysed using a previously published method. A statistical evaluation demonstrated that in head hair, the lower, middle and upper concentration ranges of 6-AM were 0.1-0.9, 0.9-12.5 and 12.5-154.1 ng/mg and those of morphine were 0.1-0.8, 0.8-6.0 and 6.0-36.3 ng/mg. In pubic hair, the lower, middle and upper concentration ranges of 6-AM were 0.2-0.5, 0.5-2.3 and 2.3-18.2 ng/mg and those of morphine were 0.2-0.4, 0.4-2.4 and 2.4-13.3 ng/mg. The morphine-to-6-AM ratio showed a large variation. The ratio tended to decrease from proximal to distal segments. The statistical results suggest low, middle and high concentration ranges which we propose can be used for estimating the amount of heroin consumed into corresponding low or occasional, regular or habitual and heavy or excessive drug use. The ratio of morphine-to-6-AM showed great variation and did not support the proposal that a ratio less than 0.77 is needed to prove ingestion of heroin.

Topics: Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Heroin Dependence; Humans; Morphine; Morphine Derivatives; Narcotics; Substance Abuse Detection

Negative motivational symptoms are observed soon after withdrawal from chronic opiate administration, and are thought to mediate dependence. Examination of brain region-specific signaling changes that accompany early withdrawal may shed light on neural mechanisms underlying negative reinforcement and dependence. Thus, we measured alterations in protein phosphorylation in multiple limbic brain regions in rats undergoing 24 h spontaneous or naltrexone-precipitated withdrawal from chronic (6 h/day) i.v. heroin self-administration. Region-specific increases in cyclic AMP-dependent GluR(1) (S845) phosphorylation were found in the nucleus accumbens shell, basolateral amygdala, hippocampal CA1 and CA3 subregions, and premotor cortex from 12 to 24 h of spontaneous withdrawal, and there were no changes in prefrontal cortex, nucleus accumbens core or caudate-putamen. Increased GluR(1) (S845) phosphorylation was detected earlier (12 h withdrawal) in the central amygdala and ventral tegmental area. In contrast, prominent increases in extracellular signal-regulated kinase phosphorylation were found in both prefrontal and premotor cortex, and CA1 and CA3 between 12 and 24 h withdrawal. Phosphorylation of striatal cyclic AMP response element binding protein increased in the caudate-putamen but not in the nucleus accumbens. Naltrexone administration after 24 h withdrawal increased extracellular signal-regulated kinase phosphorylation in the central amygdala, and nucleus accumbens core and shell. Thus, spontaneous withdrawal from heroin self-administration produces region- and time-dependent changes in cyclic AMP and extracellular signal-regulated kinase activity that could contribute to the behavioral manifestation of opiate dependence.

Topics: Analysis of Variance; Animals; Brain; Cyclic AMP Response Element-Binding Protein; Extracellular Signal-Regulated MAP Kinases; Heroin; Heroin Dependence; Male; Narcotics; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Self Administration; Serine

We have previously reported that cocaine self-administration is facilitated in male rats not residing in the test chambers (Non Resident rats) relative to rats living in the test chambers at all times (Resident rats). Surprisingly, the opposite was found for heroin.. We predicted that, when given access to both cocaine and heroin on alternate days, Non Resident rats would take more cocaine relative to heroin than Resident rats. Heroin (25.0 microg/kg) and cocaine (400 microg/kg), were made alternately available for 14 self-administration sessions, on a fixed ratio (FR) schedule that was progressively increased from FR1 to FR5. Next, some rats underwent a progressive-ratio procedure for heroin and cocaine. The other rats continued to alternate heroin and cocaine self-administration for 12 additional sessions, during which the FR schedule was progressively increased from FR10 to FR100. The second aim of the study was to investigate Fos mRNA expression in Resident and Non Resident rats treated with non-contingent intravenous infusion of "self-administration doses" of heroin (25.0 microg/kg) and cocaine (400 microg/kg).. We found that: (1) drug-taking context differentially modulates intravenous cocaine versus heroin self-administration; (2) very low doses of cocaine and heroin are sufficient to induce Fos mRNA expression in the posterior caudate; (3) drug-administration context differentially modulates cocaine- versus heroin-induced Fos mRNA expression.. Our study indicates that the context of drug taking can play a powerful role in modulating cocaine versus heroin intake in the laboratory rat.

Topics: Animals; Cocaine; Cocaine-Related Disorders; Conditioning, Operant; Gene Expression; Genes, fos; Heroin; Heroin Dependence; In Situ Hybridization; Male; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; RNA, Messenger; Self Administration; Substance Abuse, Intravenous

There is evidence that pre-exposure to drugs of abuse can induce sensitization to several of their effects.. Four experiments were conducted to investigate the effect of heroin pre-exposure on modulation of memory consolidation as indexed by heroin's action on rate of learning.. Male Sprague-Dawley rats were tested on a social recognition learning task which assesses changes in investigation during repeated exposure to the same rat (habituation training: four sessions) and during exposure to a novel rat (dishabituation test). In the first experiment, rats received 0, 0.3, or 1 mg/kg heroin s.c. immediately following each training session, or 1 mg/kg heroin 2 h post-training. In experiments 2 and 3, rats received 1 mg/kg heroin post-training after a 7-day drug-free period from heroin pre-exposure achieved through conditioned place preference (1 mg/kg s.c., 1 injection/day x 4 days) or intravenous self-administration (0.05 mg/kg/infusion i.v., 3 h/day x 9 days) training. In experiment 4, rats received 0, 0.03, 0.3, or 3 mg/kg heroin post-training after a 7-day drug-free period from a regimen of heroin administration (i.e., 1 mg/kg heroin/day s.c. x 7 days) that induced locomotor sensitization.. Post-training administration of heroin enhanced social recognition learning in a dose- and time-dependent manner. Importantly, no regimen of heroin pre-exposure significantly altered this effect of heroin.. These results do not support the hypothesis that heroin pre-exposure leads to sensitization to its effect on memory consolidation of non-drug-related learning. However, this requires further testing using alternative heroin pre-exposure regimens, a wider range of post-training heroin doses, as well as other types of learning tasks.

Topics: Animals; Association Learning; Conditioning, Operant; Dose-Response Relationship, Drug; Habituation, Psychophysiologic; Heroin; Heroin Dependence; Infusions, Intravenous; Learning; Memory; Motor Activity; Narcotics; Rats; Rats, Sprague-Dawley; Recognition, Psychology; Self Administration; Social Behavior

The study aimed to determine patterns of major depression (MD) across 36 months, and the relationship to outcomes for the treatment of heroin dependence. As part of a longitudinal cohort study, 429 heroin users were interviewed at 36 month follow-up. MD declined from 23.8% at baseline to 8.2% at 36 months. Females were more likely to have MD at both baseline (31.1 vs. 19.8) and 36 months (11.9 vs. 6.1%). Those with MD at baseline were significantly more likely to be diagnosed with MD at a follow-up interview (40.2 vs. 15.9%) and at 36 months (14.7 vs. 6.1%). Antidepressant use did not decrease across 36 months amongst either gender. Baseline MD was not related to treatment exposure across 36 months. There were large and significant declines in drug use and drug-related problems, and improvements in physical health with no group differences evident at 36 months. Despite improvements in global mental health, at both baseline and 36 months those with MD at baseline had significantly lower SF12 mental health scores. It was concluded that, with the exception of depression, the prognosis of depressed heroin users is not worse than that of non-depressed users.

Topics: Adolescent; Adult; Buprenorphine; Cohort Studies; Comorbidity; Crime; Depressive Disorder, Major; Drug Overdose; Female; Health Status; Health Status Indicators; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Middle Aged; Narcotics; Needle Sharing; New South Wales; Prognosis; Substance Abuse, Intravenous; Suicide, Attempted; Treatment Outcome; Young Adult

This is a histological report of a myocardial lesion of a 44-year-old white man who was found dead in a hotel with circumstances strongly suggestive of heroin intoxication. Based on. autopsy findings and toxicologic analysis, the present case was an instance of straight forward heroin overdose in snorter. The most striking pathologic finding of the heart was a few patches of marked dark mottling appearance in the left ventricle and ventricular septum. Histological appearance of the lesions revealed marked congestion with intramyocardial extravasation of blood. Since the deceased had patent coronary arteries without evidence of atheroma, the lesions were thought to be the results ofcoronary artery spasm. There has also been substantial evidence in the previous reports to believe that the condition is secondary to heroin-induced coronary artery spasm. However its actual underlying mechanism remains unclear.

Topics: Adult; Death, Sudden; Drug Overdose; Heart; Heroin; Heroin Dependence; Humans; Male; Myocardium

The aim of the present study was to investigate the changes in the pituitary-thyroid axis (PTA) and the time course of the hormonal alterations in subjects with opioid dependence after abstinence. Blood samples from in-patients with opioid dependence and age- and sex-matched healthy controls were collected. The severity of opioid abuse and of withdrawal symptoms was assessed. Results were compared between patients with opioid dependence (n = 30) and healthy controls (n = 30). We found that free triiodothyronine and free thyroxine levels were comparable with healthy controls while thyroid-stimulating hormone (TSH) was lower in patients in acute opioid abstinence period. Also, TSH levels in patients remained lower than controls after 30 days of abstinence. These results indicate that PTA function is altered in opioid-dependent subjects. These data highlight the importance of screening the thyroid function for individuals with chronic opioid dependence.

Topics: Adult; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Narcotics; Pituitary Gland, Anterior; Reference Values; Substance Withdrawal Syndrome; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Well-known complications related to drug abuse are myocardial insufficiency, myocardial infarction, endocarditis, myocarditis, aortic dissection, neurologic damages, ischemic colitis, thrombotic phenomenons, renal infarction and acute liver failure. Furthermore, microfocal fibrosis of the myocardium is found in stimulant abuse. The origin of myocardial fibrosis associated with opiate abuse (endocarditis, myocarditis, embolism) is still unclear. This question shall be investigated using immunohistochemical staining for early diagnosis of myocarditis. A quantification of myocardial interstitial leucocytic infiltrates was accomplished in 21 chronic drug abusers who died of heroin/morphine intoxication and compared to 15 normal subjects who died suddenly due to non-cardiac causes of death without intoxication (e.g. traffic accidents, head trauma). Toxicological investigations were performed and in addition, blood samples were checked to clarify the status of HIV, hepatitis A, B and C in both groups. To verify signs of inflammation, myocardial specimen from different locations were investigated with conventional histological stainings and immunohistochemical techniques for characterization and quantification of interstitial myocardial leucocytes, T-lymphocytes and macrophages. The number of cells were found up to fivefold increased in heroin addicts compared to the control group without reaching the cut-off values for immunohistochemically based diagnosis of myocarditis.

Topics: Adult; Aged; Chronic Disease; Female; Fibrosis; Forensic Toxicology; Heart; Heroin; Heroin Dependence; Humans; Immunohistochemistry; Male; Middle Aged; Myocarditis; Myocardium; Reference Values; Substance Abuse Detection; Young Adult

In recent decades, studies have been made of the possible benefits of treatments using heroin, although qualitative methodologies have not usually been employed. In 2004, in Granada (Spain), a clinical experiment was launched: the Experimental Narcotics Prescription Programme in Andalusia (PEPSA). This project attempted to evaluate the effectiveness of intravenous heroin and orally-administered methadone prescription for long-term socially-excluded opiate addicts for whom other treatments have failed. The research described herein is qualitative and has been carried out within the framework of the aforementioned experiment. The objective was to discover the attitudes, opinions and experiences of patients (and relatives) once they had been included in the program and are receiving heroin in a therapeutic environment.. Focused ethnographic procedures were used to establish the study population. During the field work, we carried out in-depth interviews and observations using 21 patients and relatives. Analysis was carried out by a team according to grounded theory.. Our results show how the treatment process and the administering of heroin in a therapeutic context manages to break the habit of consuming heroin obtained illegally, thus changing the significance given to the substance and bringing about improvements in aspects such as the workplace, family relations and physical and mental health.. The move from 'substance addiction' to chronic 'illness' upon beginning the treatment provides a chance for a population with a long history of rejection and exclusion to become part of society once again.

Topics: Adult; Drug Administration Schedule; Drug Prescriptions; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Narcotics; Qualitative Research; Social Support; Spain; Substance Abuse, Intravenous

There still are concerns about unwanted effects of harm-reduction measures that may lead to an increasing number of new heroin users. Furthermore, it is thought that the admission of a substantial proportion of heroin users to methadone treatments reduces the demand on the heroin market and thus results in a lower price for street heroin. And finally, the intensity of police activity in the drug field may also affect prices for street heroin.. As incidence of regular heroin use over more than a decade is rarely known elsewhere, we examined the Zurich experience between 1980 and 2005 by triangulating published and unpublished data, concerning heroin price, heroin purity level, heroin seizures and drug offences. This time period encompasses the time before and after the introduction of low-threshold methadone treatment in 1991.. We found a steep peak of heroin incidence in 1990. The street price of heroin already declined from 700 to 60 Swiss Francs during the 80s. The number of heroin consumptions possession offences reported by the police increased since 1991 and peaked in 1997, 2 years after the closure of the last open drug scene.. The introduction of low-threshold methadone treatment has not resulted in lower heroin prices and the increased police activity during the 90s has not led to higher heroin prices, even though the higher police activity in the late 90s may have contributed to the prevention of a re-establishment of open drug scenes. In conclusion, we did not find a close relationship between street prices of heroin, police activity, and incidence of problematic heroin use.

Topics: Analgesics, Opioid; Commerce; Crime; Drug and Narcotic Control; Drug Contamination; Government Regulation; Harm Reduction; Heroin; Heroin Dependence; Humans; Illicit Drugs; Incidence; Law Enforcement; Methadone; Police; Public Policy; Switzerland; Time Factors

Self-injurious behaviours (SIB) can provide useful criteria for subtyping heroin-dependent patients, since SIB have been related to an opioid system dysfunction and they hinder patient management. The frequency of nine varieties of moderate/superficial SIB during active heroin use was assessed retrospectively in 164 heroin-dependent patients. A principal component analysis of SIB episodes revealed a four-component solution which accounted for 69.3% of the variance. The components were named as follows (percentage of variance explained by each component is enclosed in parentheses): 'SIB with objects' (27.3%), 'SIB by biting/scratching/hair-pulling' (18.2%), 'SIB by hitting' (12.3%), and 'SIB by picking scabs' (11.5%). A cluster analysis using the results of the principal component analysis enabled us to define three types of heroin-dependent patients, labelled: 'low-occurrence SIB cluster' (59.8%), 'high-occurrence scab-picking cluster' (31.7%) and 'high-occurrence hitting and cutting cluster' (8.5%). SIB by hitting was the most discriminatory component among clusters: its frequency was at a minimum in the low-occurrence SIB cluster, and attained a maximum in the high-occurrence hitting and cutting cluster. However, there were no differences among clusters regarding heroin-use variables. Patients from the low-occurrence SIB cluster, compared with those from the other two clusters, reported fewer episodes of SIB or suicide attempts and were diagnosed less frequently with bulimia. Patients from the high-occurrence scab-picking cluster had a very frequent history of these SIB, while the opposite was true in patients from the high-occurrence hitting and cutting cluster. Patients from this cluster probably presented staff members with the main management problems.

Topics: Adolescent; Adult; Bulimia Nervosa; Cluster Analysis; Comorbidity; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Principal Component Analysis; Self-Injurious Behavior; Suicide, Attempted; Surveys and Questionnaires

There are several complications associated with heroin abuse, some of which are life-threatening. Methadone may aggravate this problem.. A clinical case description.. A 33-year-old man presented with rhabdomyolysis and cerebral ischemic stroke after intravenous heroin. He had used heroin since age 20, and had used 150 mg methadone daily for 6 months. He was found unconsciousness at home and was sent to our hospital. In the ER, his opiate level was 4497 ng/ml. In the ICU, we found rhabdomyolysis, acute renal failure and acute respiratory failure. After transfer to an internal ward, we noted aphasia and weakness of his left limbs. After MRI, we found cerebral ischemic infarction.. Those using methadone and heroin simultaneously may increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone maintenance therapy should be warned regarding these serious adverse events. Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are discussed.

Topics: Adult; Brain; Brain Damage, Chronic; Cerebral Cortex; Cerebral Hemorrhage; Cerebral Infarction; Dominance, Cerebral; Drug Interactions; Electroencephalography; Heroin; Heroin Dependence; Humans; Intensive Care Units; Magnetic Resonance Imaging; Male; Methadone; Narcotics; Rhabdomyolysis; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Tomography, X-Ray Computed

Although morphine and heroin analgesia is mediated by mu-opioid receptors encoded by the MOR-1 gene, distinct isoforms are involved. Both opioids also induce dependence by acting at mu-opioid receptors, but which variants are utilized is not known. Here, we assayed morphine and heroin analgesia and dependence in mice treated with antisense oligodeoxynucleotides (AO) targeting MOR-1 exons 1-4. Whereas AOs targeting exons 1 and 4 blocked morphine analgesia, those targeting exons 2 and 3 blocked heroin analgesia. Neither morphine nor heroin analgesia was compromised 5 days after the last AO injection. In morphine and heroin dependent mice, only exon 1 AO significantly reduced jumping incidence during naloxone (50mg/kg) precipitated withdrawal. Neither analgesia nor withdrawal jumping was attenuated in controls pretreated with saline or a mismatch oligodeoxynucleotide control sequence. While these data confirm previous reports that morphine and heroin analgesia are not mediated by a single mu-opioid receptor, both opiates nonetheless apparently induce dependence via a mu-opioid receptor isoform containing exon 1. For heroin, the possibility that analgesia and dependence are mediated by distinct mu-opioid receptor isoforms offers the prospect of developing potent opiate analgesics possessing reduced dependence liability.

Topics: Analgesia; Analgesics, Opioid; Analysis of Variance; Animals; Exons; Heroin; Heroin Dependence; Hot Temperature; Male; Mice; Morphine; Morphine Dependence; Motor Activity; Naloxone; Narcotic Antagonists; Oligonucleotides, Antisense; Pain Measurement; Protein Isoforms; Receptors, Opioid, mu; Substance Withdrawal Syndrome

Despite the large volume of public effort devoted to restrain drug supply and the growing attention given to drug demand reduction policies, the use of cocaine and heroin remains steady. Furthermore, retail drug prices have fallen significantly in Europe and the US. This puzzling evidence leads us to develop a model aiming at systematically analysing illicit drug markets.. We model the markets of cocaine and heroin from production to the final retail markets. One novelty of the analysis consists in characterising the retail market as a monopolistic competitive one. Then, upper level dealers have some market power in the retail market. This allows them to charge a markup and to earn extra profits. These extra profits attract newcomers so that profits tend to fall over time.. Theoretical model was used to analyse the effect of supply containment policies on the retail market, the producer market and the export-import business. This introduces the discussion of the impact of demand reduction policies on the high level traffickers' profit. Finally, globalisation enters in the model.. Law enforcement measures increase the risk premia received by the lower and higher level traffickers. Consequently, trafficking intermediation margins tend to increase. However, globalisation has the opposite effect. It lowers intermediation margins and, then, pushes retail prices down, thereby stimulating consumption. In doing so, globalisation offsets the effects of supply containment policies. Finally, we discuss how the effectiveness of supply containment policies can be enhanced by combining them with demand reduction policies.

Topics: Cocaine; Cocaine-Related Disorders; Commerce; Crime; Drug and Narcotic Control; Government Regulation; Heroin; Heroin Dependence; Humans; Illicit Drugs; Internationality; Law Enforcement; Models, Economic; Public Policy; Time Factors

In humans, exposure to environmental contexts previously associated with heroin intake can provoke relapse to drug use. In rats, exposure to heroin-associated contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by blockade of D(1)-family receptors in lateral or medial accumbens shell, but not accumbens core.. In this study, we further characterized the role of striatal D(1)-family receptors in context-induced reinstatement by assessing the effect of dorsolateral or dorsomedial injections of the D(1)-family receptor antagonist SCH 23390 on this reinstatement.. Rats were trained to self-administer heroin (0.05-0.10 mg/kg per infusion) for 12 days; drug infusions were paired with a discrete tone-light cue. Subsequently, heroin-reinforced lever pressing was extinguished in the presence of the discrete cue in a nondrug context. During reinstatement tests under extinction conditions, the D(1)-family receptor antagonist SCH 23390 (0.3-1.0 microg per side) was injected into the dorsolateral or dorsomedial striatum prior to exposure to heroin self-administration context or the nondrug (extinction) context. We then used a disconnection procedure to examine whether D(1)-family receptors in the dorsolateral striatum and lateral accumbens shell jointly or independently support context-induced reinstatement.. Dorsolateral but not dorsomedial SCH 23390 injections attenuated context-induced reinstatement of heroin seeking. SCH 23390 injections into the dorsolateral striatum of one hemisphere and lateral accumbens shell of the other hemisphere were ineffective.. Results indicate that dorsolateral striatum D(1)-family dopamine receptors are critical for context-induced reinstatement of heroin seeking. Results also suggest that D(1)-receptor-mediated dopamine transmission in the dorsolateral striatum and lateral accumbens shell independently support this reinstatement.

Topics: Animals; Behavior, Addictive; Behavior, Animal; Benzazepines; Conditioning, Psychological; Corpus Striatum; Disease Models, Animal; Extinction, Psychological; Heroin; Heroin Dependence; Male; Nucleus Accumbens; Rats; Rats, Long-Evans; Receptors, Dopamine D1; Reinforcement Schedule; Reward; Secondary Prevention; Self Administration

Topics: Adult; Cerebral Cortex; Cerebral Infarction; Drug Synergism; Globus Pallidus; Heroin; Heroin Dependence; Humans; Male; Methadone; Narcotics; Neurologic Examination; Rhabdomyolysis; Substance Abuse Treatment Centers; Substance Abuse, Intravenous

Heroin use and withdrawal cause abnormality in the endocrine system. However, the time course of neuroendocrine alterations in heroin addicts during pharmacologically unassisted withdrawal is still unclear.. To investigate alterations in cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), leptin, and neuropeptide Y (NPY) during the first month of abstinence in heroin addicts.. Twelve heroin addicts and eight matched healthy control subjects were recruited for this study. The neuroendocrine alterations and self-reported heroin craving, anxiety, and depression in heroin addicts were assessed at different time points (days 3, 10, and 30) of first month of abstinence from heroin use.. Self-reported heroin craving, anxiety, and depression in heroin addicts decreased gradually during the first month of abstinence. The cortisol levels increased from abstinence day 3 to 30, while ACTH and beta-EP levels decreased over this period in heroin addicts. The leptin and NPY levels were significantly decreased on days 3 and 10 but had normalized on day 30 of abstinence. A positive correlation between cortisol level and heroin craving, anxiety, and depression was observed, while a negative correlation was observed between beta-EP level and craving and anxiety and between leptin and depression and NPY and anxiety.. Abnormal alterations in the neuroendocrine system, including levels of cortisol, ACTH and beta-EP persist throughout the first month of abstinence. These results suggest that neuroendocrine system dysfunctions in heroin abusers is independent of the acute and protracted withdrawal syndromes, and may thus contribute to relapse to heroin use.

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; Anxiety; beta-Endorphin; Case-Control Studies; Depression; Heroin; Heroin Dependence; Humans; Hydrocortisone; Leptin; Male; Neuropeptide Y; Neurosecretory Systems; Patient Selection; Psychiatric Status Rating Scales; Radioimmunoassay; Substance Withdrawal Syndrome; Time Factors

Experiencing previous non-fatal overdoses have been identified as a predictor of subsequent non-fatal overdoses; however, few studies have investigated the association between previous non-fatal overdose experiences and overdose mortality. We examined overdose mortality among injecting drug users who had previously been attended by an ambulance for a non-fatal heroin overdose.. Using a retrospective cohort design, we linked data on non-fatal heroin overdose cases obtained from ambulance attendance records in Melbourne, Australia over a 5-year period (2000-2005) with a national death register.. 4884 people who were attended by ambulance for a non-fatal heroin overdose were identified. One hundred and sixty-four overdose deaths occurred among this cohort, with an average overdose mortality rate of 1.20 per 100 person-years (95% CI, 1.03-1.40). Mortality rate decreased 10-fold after 2000 coinciding with widely reported declines in heroin availability. Being male, of older age (>35 years) and having been attended multiple times for previous non-fatal overdoses were associated with increased mortality risk.. As the first to show a direct association between non-fatal overdose and subsequent overdose mortality, this study has important implications for the prevention of overdose mortality. This study also shows the profound effect of macro-level heroin market dynamics on overdose mortality.

Topics: Adult; Age Factors; Ambulances; Cohort Studies; Death Certificates; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Medical Record Linkage; Registries; Retrospective Studies; Risk Factors; Sex Factors; Substance Abuse, Intravenous; Victoria; Young Adult

Thailand has traditionally pursued an aggressive enforcement-based anti-illicit drug policy in an effort to make the country "drug-free." In light of this ongoing approach, we sought to assess impacts of enforcement on drug use behaviors among a cohort of injection drug users (IDU) in Thailand. We examined drug use patterns among IDU participating in a cross-sectional study conducted in Bangkok (n = 252). Participants were asked to provide data regarding patterns of drug use in the previous six months, including types of drugs consumed, method of consumption, frequency of use, and weekly income spent on drugs. We also conducted bivariate analyses to identify a possible effect of a reported increase in police presence on measures of drug use and related risk behaviors among study participants. One hundred fifty-five (61.5%) individuals reported injection heroin use and 132 (52.4%) individuals reported injection midazolam use at least daily in the past six months. Additionally, 86 (34.1%) individuals reported at least daily injection Yaba and Ice (i.e., methamphetamine) use. Participants in our study reported high levels of illicit drug use, including the injection of both illicit and licit drugs. In bivariate analyses, no association between increased police presence and drug use behaviors was observed. These findings demonstrate high ongoing rates of drug injecting in Thailand despite reports of increased levels of strict enforcement and enforcement-related violence, and raise questions regarding the merits of this approach.

Topics: Adult; Analgesics, Opioid; Central Nervous System Stimulants; Cross-Sectional Studies; Drug and Narcotic Control; Drug Users; Drug Utilization; Female; Heroin; Heroin Dependence; Humans; Hypnotics and Sedatives; Illicit Drugs; Law Enforcement; Male; Methamphetamine; Midazolam; Police; Substance Abuse, Intravenous; Surveys and Questionnaires; Thailand

A number of gene expression studies have investigated changes induced by drug exposure, but few reports describe changes that persist following relapse. In this study, genome-wide analysis of gene expression was conducted following an extinction session (90 min) in rats that expressed behavioral incubation of heroin-seeking and goal-directed behavior. As an important modulator of goal-directed behavior, the medial prefrontal cortex (mPFC) was the target of genomic analysis. Rats were trained to self-administer heroin during 3 h daily sessions for 14 d. Following the self-administration period, rats were reintroduced to the self-administration chambers for a 90-minute extinction session in which they could seek heroin, but received none. Extinction sessions were conducted on groups after either 1 d or 14 d of drug-free enforced abstinence to demonstrate behavioral incubation.. Behavioral data demonstrated incubation (increased expression) of heroin-seeking and goal-directed behavior after the 14 d abstinent period. That is, following 14 d of enforced abstinence, animals displayed heightened drug-seeking behavior when returned to the environment where they had previously received heroin. This increased drug-seeking took place despite the fact that they received no drug during this extinction session. Whole genome gene expression analysis was performed and results were confirmed by quantitative real-time PCR (RT-qPCR). Microarrays identified 66 genes whose expression was identified as changed by at least 1.4 fold (p < 0.02) following 14 d of abstinence and the 90-minute extinction session compared to the saline treated controls. Orthogonal confirmation by RT-qPCR demonstrated significant alterations in bdnf, calb1, dusp5, dusp6, egr1, npy, rgs2.. Ontological analysis indicates that several of the genes confirmed to be changed are important for neuroplasticity, and through that role may impact learning and behavior. The importance of drug-seeking behavior and memory of previous drug-taking sessions suggest that such genes may be important for relapse. The global gene expression analysis adds to the knowledge of heroin-induced changes and further highlights similarities between heroin and other drugs of abuse.

Topics: Animals; Behavior, Addictive; Conditioning, Operant; Extinction, Psychological; Gene Expression Profiling; Heroin; Heroin Dependence; Nerve Tissue Proteins; Oligonucleotide Array Sequence Analysis; Prefrontal Cortex; Rats; Reverse Transcriptase Polymerase Chain Reaction; Self Administration; Up-Regulation

Topics: Drug and Narcotic Control; Drug Prescriptions; Heroin; Heroin Dependence; History, 20th Century; Humans; Illicit Drugs; Methadone; Narcotics; Politics; United Kingdom; United States

Numerous studies have documented cognitive impairments and hypoactivity in the prefrontal and anterior cingulate cortices in drug users. However, the relationships between opiate dependence and brain structure changes in heroin users are largely unknown. In the present study, we measured the density of gray matter (DGM) with voxel-based morphometry in 30 lifetime heroin-dependent individuals who had abstained from drug use for 5 months, and 34 healthy participants. The DGM of the prefrontal, temporal and cingulate cortices significantly decreased in heroin addicts relative to the healthy group. Critically, partial correlation analysis, which controlled for age, education and gender factors as well as nicotine use and heroin abstinence duration, showed that the duration of heroin use negatively correlated with the DGM in heroin-dependent individuals. These results provide compelling evidence for structural abnormality in heroin-dependent individuals and further suggest that duration of heroin use is a critical factor leading to brain damage.

Topics: Adult; Age Factors; Analysis of Variance; Brain Mapping; Cerebral Cortex; Diagnostic and Statistical Manual of Mental Disorders; Drug Users; Female; Heroin; Heroin Dependence; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Organ Size; Sex Factors; Time Factors

Topics: Australia; Caregivers; Drug Overdose; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists; Peer Group; Self Care

Topics: Directly Observed Therapy; Heroin; Heroin Dependence; Humans; Injections; Narcotics; Randomized Controlled Trials as Topic

There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse.

Topics: Animals; Cannabidiol; Cannabinoid Receptor Modulators; Conditioning, Psychological; Cues; Disease Models, Animal; Glutamic Acid; Heroin; Heroin Dependence; Limbic System; Male; Narcotic Antagonists; Narcotics; Neural Pathways; Nucleus Accumbens; Rats; Rats, Long-Evans; Receptor, Cannabinoid, CB1; Receptors, AMPA; Treatment Outcome; Ventral Tegmental Area

To study the changes of neutral alpha-glucoside activity in the epididymis of heroin-dependent and heroin-withdrawal rats, and to investigate the effects of intervention with purine nucleotide (AMP and GMP).. Eighty Wistar rats were randomly divided into 8 groups of equal number, control, nucleotide, heroin, heroin + nucleotide, 3 d withdrawal, 9 d withdrawal, 3 d nucleotide (nucleotide administrated for 3 days after heroin withdrawal) and 9 d nucleotide (nucleotide administrated for 9 days after heroin withdrawal). Neutral alpha-glucosidase activity in the epididymis was detected in each group of rats.. Compared with the control group, neutral alpha-glucoside activity was markedly decreased in the heroin group (P < 0.05), and also in the 3 d and 9 d withdrawal groups, although with no significant differences (P > 0.05).. Heroin reduces neutral alpha-glucoside activity in the epididymis of rats, and this effect may continue for some time after drug withdrawal, while purine nucleotide can keep neutral alpha-glucosidase activity in a relatively stable state.

Topics: alpha-Glucosidases; Animals; Epididymis; Heroin; Heroin Dependence; Male; Purine Nucleotides; Rats; Rats, Wistar

Topics: Heroin; Heroin Dependence; Humans; Methadone; Practice Guidelines as Topic

Topics: Analgesics, Opioid; Heroin; Heroin Dependence; Humans; Politics; Prejudice; Randomized Controlled Trials as Topic; Research Design; Spain

In September, the U.K. released positive results of evaluations of a heroin prescription trial, resulting in a call from the National Treatment Agency for Substance Misuse to expand the projects nationwide.

Topics: Directly Observed Therapy; Drug Prescriptions; Heroin; Heroin Dependence; United Kingdom

Topics: Australia; Crime; Heroin; Heroin Dependence; Humans; Narcotics

Non-fatal overdose among injection drug users (IDU) is a source of significant morbidity. Since it has been suggested that supervised injecting facilities (SIF) may increase risk for overdose, we sought to evaluate patterns of non-fatal overdose among a cohort of SIF users. We examined recent non-fatal overdose experiences among participants enrolled in a prospective study of IDU recruited from within North America's first medically supervised safer injecting facility. Correlates of recent non-fatal overdoses were identified using generalized estimating equations (GEE). There were 1,090 individuals recruited during the study period of which 317 (29.08%) were female. At baseline, 638 (58.53%) reported a history of non-fatal overdose and 97 (8.90%) reported at least one non-fatal overdose in the last six months. This proportion remained approximately constant throughout the study period. In the multivariate GEE analysis, factors associated with recent non-fatal overdose included: sex-trade involvement (Adjusted Odds Ratio [AOR]: 1.45 [95% Confidence Interval [CI] 1.07-1.99], p = 0.02) and public drug use (AOR: 1.50 [95% CI 1.09-2.06]; p = 0.01). Using the SIF for >or= 75% of injections was not associated with recent non-fatal overdose in univariate (Odds Ratio: 1.05, p = 0.73) or multivariate analyses (AOR: 1.01, p = 0.96). The proportion of individuals reporting recent non-fatal overdose did not change over the study period. Our findings indicate that a sub-population of IDU might benefit from overdose prevention interventions. Our findings refute the suggestion that the SIF may increase the likelihood of overdose.

Topics: Adult; Age Factors; Aged; Canada; Cohort Studies; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Incidence; Injections, Intravenous; Male; Patient Selection; Prevalence; Prospective Studies; Recurrence; Substance Abuse Treatment Centers; Substance Abuse, Intravenous

Numerous findings suggest that drug seeking and ingestive behaviors share common neurobiological mechanisms, but the relevant pathways are unknown. Dietary manipulations result in changes in endocrine the and/or neuropeptide signals, such as the hormones leptin and ghrelin, which are dynamically linked to energy balance and the regulation of feeding behavior. We have recently demonstrated that food deprivation-induced reinstatement of heroin seeking can be blocked with leptin, and others have suggested a role for ghrelin in drug-related behaviors. The feeding-relevant effects of leptin and ghrelin involve the inhibition or activation, respectively, of neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus. However, the effects of NPY, a highly potent orexigenic peptide, on drug-related behaviors have not been thoroughly studied. Here we examined the effect of acute NPY administration on the rate of heroin self-administration and the reinstatement of extinguished heroin-seeking behavior. Heroin intake (0.05mg/kg/infusion) was tested using a self-administration procedure (FR-1), 10-min post-NPY injections (0.0, 4.0, and 10microg/rat, ICV). In a different group of rats, NPY-induced reinstatement (0.0, 4.0, and 10microg/rat, ICV) of extinguished heroin seeking was assessed. NPY injections increased on-going heroin self-administration, and induced a reinstatement of extinguished heroin-seeking behavior. These findings suggest that NPY can modulate the rewarding and conditioned reinforcing effects of drugs of abuse.

Topics: Animals; Behavior, Animal; Conditioning, Operant; Disease Models, Animal; Food Deprivation; Heroin; Heroin Dependence; Male; Narcotics; Neuropeptide Y; Rats; Rats, Long-Evans; Reinforcement Schedule; Reinforcement, Psychology; Self Administration

To investigate the role of oligodendrocyte apoptosis under the regulation of the bcl-2/bax protein expression in brain white matter in the pathogenesis of heroin-induced spongiform leucoencephalopathy (HSLE).. Samples of frontal lobe, cerebellum, and corpus callosum were obtained from the brains during autopsy of 4 HSLE cases and 5 normal controls and underwent light microscopy and electron microscopy. Immunocytochemistry was used to detect the expression of myelin basic protein (MBP), caspase-3, bcl-2 protein, and bax protein.. Widespread demyelination was seen in the white matter of the frontal lobe, cerebellum and corpus callosum of the HSLE cases, most severely in the cerebellum. The levels of caspase-3 and bax expression of the HSLE group were significantly higher than those of the control group (both P <0.05) , however, the bcl-2 level of the HSLE group was no significantly different from that of the control group (P > 0.05).. Widespread demyelination in the white matter is a prevailed pathological change of HSLE. Oligodendrocyte apoptosis under induced by the decrease of bcl-2/bax ratio may contribute to the pathogenesis.

Topics: Adult; Aged; Apoptosis; Autopsy; bcl-2-Associated X Protein; Canavan Disease; Female; Heroin; Heroin Dependence; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Myelin Basic Protein; Oligodendroglia; Proto-Oncogene Proteins c-bcl-2

A 12-year medicolegal investigation of deceased illegal drug users (ILDU) in Stockholm, Sweden, classified on the basis of postmortem chemical tests, showed noticeable variations in causes and manners of death as well as in the distribution of suicide methods. This study offers objective information about connection between the postmortem findings of illegal drugs and the causes and manners of death of their users. However, further studies, comparing prevalence of drug use in general population and at the postmortem tests, are needed for more detailed elucidation of this connection.

Topics: Adolescent; Adult; Aged; Amphetamine; Amphetamine-Related Disorders; Cause of Death; Diagnosis; Female; Heroin; Heroin Dependence; Humans; Male; Marijuana Abuse; Methadone; Middle Aged; Suicide; Sweden

The purpose of this study was to investigate the role of the ventromedial prefrontal cortex (vmPFC) in the expression of extinguished heroin seeking as measured by conditioned place preference (CPP) in males Sprague-Dawley rats (n=25). Heroin place conditioning (0.3mg/kg SC x 4 sessions) was followed by a test of preference 24h later, extinction (saline x 4 sessions), heroin reconditioning (saline or 1.0mg/kg x 1 session), and a second test of place preference 24h later. Fifteen minutes prior to this test, rats received intra-vmPFC infusions (bilateral, 0.5 microl/side) of a mixture of GABA(A) (muscimol; 0.03 nmol) and a GABA(B) (baclofen; 0.3 nmol) agonists, or vehicle. As expected on the basis of previous studies, reconditioning with heroin resulted in the re-emergence of a CPP. Importantly, inactivation of the vmPFC produced the same effect in animals that did not receive heroin on the session of reconditioning. These results indicate that the vmPFC modulates expression of extinguished heroin seeking and suggest that prefrontal inhibitory mechanisms are involved in relapse to drug seeking.

Topics: Analysis of Variance; Animals; Baclofen; Behavior, Animal; Conditioning, Operant; Extinction, Psychological; GABA Agonists; GABA Antagonists; Heroin; Heroin Dependence; Inhibition, Psychological; Male; Muscimol; Narcotics; Prefrontal Cortex; Rats; Rats, Sprague-Dawley

To investigate the expression of caspase 3 in the brain regions related to addiction, learning and memory in mice prenatally exposed to heroin and to ascertain whether postnatal apoptotic mechanism participates in neurobehavioral teratogenicity induced by maternal heroin abuse.. A mouse model was established by administration of diacetylmorphine (heroin, purity 98.5%, product ID No.171206-200614) 10 mg/(kg x d) subcutaneously to pregnant BALB/c mice on embryonic day (E)E8-E18. The offspring were divided into heroin(Her) and saline(Sal) groups according to the maternal treatment. The expression of caspase 3 in prefrontal lobe cortex(PFC), hippocampus(HP) and nucleus accumbens(Acb) was detected by RT-PCR and Western blot on mouse postnatal day(P)14.. The mRNA and protein expression of caspase 3 were significantly increased in the areas of PFC, HP and Acb in Her group compared with Sal group(P < 0.05).. E8-E18 prenatal exposure to heroin can induce apoptosis through caspase 3 activation in brain regions related to addiction, learning and memory, which indicates that apoptotic mechanism may be involved in neurobehavioral teratogenicity by heroin exposure in uterus.

Topics: Animals; Caspase 3; Disease Models, Animal; Female; Gene Expression; Heroin; Heroin Dependence; Hippocampus; Humans; Learning; Male; Maternal Exposure; Memory; Mice; Mice, Inbred BALB C; Nucleus Accumbens; Prefrontal Cortex; Pregnancy

In the Swiss heroin substitution trials, patients are treated with self-administered diacetylmorphine (heroin). Intravenous administration is not possible in patients that have venosclerosis. Earlier studies have demonstrated that oral diacetylmorphine may be used, although it is completely converted to morphine presystemically. Morphine bioavailability after high-dose oral diacetylmorphine is considerably higher than would be predicted from low-dose trials. The aim was to investigate whether the unexpectedly high bioavailability is due to a difference in the drug examined, and whether it depends on previous exposure or on dose.. Opioid-naive healthy volunteers and dependent patients from the Swiss heroin trials (n = 8 per group) received low doses of intravenous and oral deuterium-labelled morphine and diacetylmorphine, respectively. Patients also received a high oral diacetylmorphine dose.. The maximum plasma concentration (C(max)) of morphine was twofold higher after oral diacetylmorphine than after morphine administration in both groups. However, morphine bioavailability was considerably higher in chronic users [diacetylmorphine 45.6% (95% confidence interval 40.0, 51.3), morphine 37.2% (30.1, 44.3)] than in naive subjects [diacetylmorphine 22.9% (16.4, 29.4), morphine 23.9% (16.5, 31.2)] after low oral doses (48.5 micromol) of either diacetylmorphine or morphine. Morphine clearance was similar in both groups. Moreover, oral absorption of morphine from diacetylmorphine was found to be dose dependent, with bioavailability reaching 64.2% (55.3, 73.1) for high diacetylmorphine doses (1601 micromol).. Oral absorption of opioids is substance-, dose- and patient collective-dependent, suggesting that there may be a saturation of first-pass processes, the exact mechanism of which is not yet understood.

Topics: Administration, Oral; Adult; Analgesics, Opioid; Biological Availability; Dose-Response Relationship, Drug; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Morphine; Young Adult

The aim of the study was to assess perinatal outcome of pregnancy burdened with maternal addiction in comparison with an unselected population from a European transition country.. Data on pregnancies complicated by illicit drug abuse (n = 85) managed during a 10-year period (1997-2007) at Split University Hospital were analyzed. Data on the type of drug, course of gestation and labor, and on perinatal outcome were considered. Data on all non-dependence pregnancies recorded during the study period were used as a control group.. During the study period, there were 85 dependence-complicated pregnancies (0.2%). Use of heroin alone during pregnancy was recorded in 51 women (50%), methadone alone in 6 (7%), and a combination of heroin and methadone in 9 (11%). Premature delivery was significantly more common in the group of pregnant addicts (21% vs. 6%); 49% of pregnant addicts were carriers of hepatitis C virus (HCV) and 14% of hepatitis B virus (HBV). Neonatal abstinence syndrome developed in 61 infants (7%) born to addicted mothers. There were 4 cases (4.6%) of early neonatal death; 7 neonates had 5-minute Apgar score < or = 7 (8%); 29 neonates had low birth weight for age (33%); and 7 neonates had congenital anomalies (8%). The risk of various congenital anomalies was 3-fold in the group of children born to addicted mothers.. Addiction pregnancies present a small but high-risk group according to perinatal outcome. Appropriate obstetric and neonatal care can reduce the rate of complications in these pregnancies and improve perinatal outcome.

Topics: Adult; Apgar Score; Birth Weight; Croatia; Female; Heroin; Heroin Dependence; Humans; Incidence; Infant Mortality; Infant, Newborn; Maternal Exposure; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy Outcome

Heroin administration alters the induction of nitric oxide, a molecule known to play a critical role in immune function. Previous research has shown that these alterations can be conditioned to environmental stimuli that have been associated with drug administration. Little is known about the brain areas that mediate these effects; however, the basolateral amygdala (BLA) has been implicated in the formation of stimulus-reward associations within models of drug abuse. The present study sought to determine whether inactivation of the BLA would alter heroin's conditioned effects on the expression of inducible nitric oxide synthase (iNOS) and the proinflammatory cytokines TNF-alpha and IL-1beta in the rat. The conditioning procedure involved repeated pairing of heroin with placement into a standard conditioning chamber. To test the conditioned response, animals were returned to the previously drug-paired environment 6 days after the final conditioning session. Prior to testing, animals received intra-BLA microinfusions of a mixture of the GABA agonists muscimol and baclofen. Following removal from the chambers on test day, all animals received subcutaneous lipopolysaccharide to induce systemic expression of iNOS, TNF-alpha and IL-1beta. Analyses using real-time RT-PCR indicated that inactivation of the BLA blocked the suppressive effect of heroin-associated environmental stimuli on iNOS induction and on the expression of the proinflammatory cytokines TNF-alpha and IL-1beta in spleen and liver tissue. This study is important because it is the first to demonstrate that heroin's conditioned effects on proinflammatory mediators require the BLA. These findings may have significant implications for the treatment of heroin users.

Topics: Amygdala; Animals; Conditioning, Psychological; Encephalitis; GABA Agonists; Heroin; Heroin Dependence; Inflammation Mediators; Interleukin-1beta; Lipopolysaccharides; Liver; Male; Narcotics; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Rats, Inbred Lew; RNA, Messenger; Spleen; Tumor Necrosis Factor-alpha

Clenbuterol is a potent, long-acting beta-adrenergic agonist that has been reported as an adulterant of heroin. We describe an atypical syndrome in five users of clenbuterol-tainted heroin.. All cases were referred to a regional Poison Control Center. Urine and blood were analyzed using gas and liquid chromatography as well as mass spectrometry.. Five heroin users presented with a syndrome characterized by muscular spasm, tremor, hyperreflexia, and elevated serum creatine phosphokinase concentrations. All patients lacked findings of acute clenbuterol toxicity but tested positive for clenbuterol and negative for strychnine and a battery of common potential adulterants.. We report five cases of a novel neuromuscular syndrome in users of clenbuterol-adulterated heroin. It is unclear whether these reactions represent an atypical response to clenbuterol or another unidentified contaminant.

Topics: Adult; Clenbuterol; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Neuromuscular Diseases

Topics: Adrenergic beta-Agonists; Adult; Clenbuterol; Diagnosis, Differential; Drug Contamination; Heroin; Heroin Dependence; Humans; Hypokalemia; Illicit Drugs; Male; Tachycardia

Associative learning processes have an important role in the initiation and persistence of heroin-seeking. Here we show in a rat self-administration model that reexposure to cues previously associated with heroin results in downregulation of AMPA receptor subunit GluR2 and concomitant upregulation of clathrin-coat assembly protein AP2ml in synaptic membranes of the medial prefrontal cortex (mPFC). Reduced AMPA receptor expression in synaptic membranes was associated with a decreased AMPA/NMDA current ratio and increased rectification index in mPFC pyramidal neurons. Systemic or ventral (but not dorsal) mPFC injections of a peptide inhibiting GluR2 endocytosis attenuated both the rectification index and cue-induced relapse to heroin-seeking, without affecting sucrose-seeking. We conclude that GluR2 receptor endocytosis and the resulting synaptic depression in ventral mPFC are crucial for cue-induced relapse to heroin-seeking. As reexposure to conditioned stimuli is a major cause for heroin relapse, inhibition of GluR2 endocytosis may provide a new target for the treatment of heroin addiction.

Topics: Acoustic Stimulation; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Analysis of Variance; Animals; Behavior, Animal; Cues; Endocytosis; Excitatory Amino Acid Agonists; Extinction, Psychological; Gene Expression Regulation; Heroin; Heroin Dependence; In Vitro Techniques; Male; Membrane Potentials; N-Methylaspartate; Narcotics; Neuronal Plasticity; Neurons; Patch-Clamp Techniques; Peptides; Prefrontal Cortex; Rats; Rats, Wistar; Receptors, AMPA; Reinforcement Schedule; Reinforcement, Psychology; Self Administration; Sucrose; Tandem Mass Spectrometry

Hearing loss is an infrequently-reported consequence of recreational drug abuse. Although there are sporadic reports of hearing loss from heroin and cocaine ingested separately, there are no reports of hearing loss resulting from the combination of both drugs ingested simultaneously in the form of speedballing.. The purpose of this report is to document a case of bilateral sensorineural hearing loss associated with an episode of speedballing.. Case Report.. The subject of this report was a 40-year-old man with a 20-year history of substance abuse. Data collected included a case history, pure tone audiometry, tympanometry and acoustic reflexes, and transient evoked otoacoustic emissions.. The audiologic evaluation indicated a mild to moderate, relatively flat, bilateral sensorineural hearing loss that was worse in the right ear.. A bilateral sensorineural hearing loss involving both cochlear and neural pathology may be a rare complication of cocaine, heroin, or the combination of the two drugs.

Topics: Acoustic Impedance Tests; Adult; Audiometry, Pure-Tone; Cocaine; Cocaine-Related Disorders; Diagnosis, Differential; Drug Synergism; Hearing Loss, Bilateral; Hearing Loss, Sudden; Heroin; Heroin Dependence; Humans; Male; Otoacoustic Emissions, Spontaneous; Reflex, Acoustic; Retrocochlear Diseases; Tinnitus; Vestibulocochlear Nerve

A previous study has shown that the stress responsive neurohormone arginine vasopressin (AVP) is activated in the amygdala during early withdrawal from cocaine. The present studies were undertaken to determine whether (1) AVP mRNA levels in the amygdala or hypothalamus, as well as hypothalamic-pituitary-adrenal (HPA) activity, would be altered during chronic intermittent escalating heroin administration (10 days; 7.5-60 mg/kg/day) or during early (12 h) and late (10 days) spontaneous withdrawal; (2) foot shock stress would alter AVP mRNA levels in the amygdala or hypothalamus in rats withdrawn from heroin self-administration (7 days, 3 h/day, 0.05 mg/kg/infusion); and (3) the selective V1b receptor antagonist SSR149415 (1 and 30 mg/kg, intraperitoneal) would alter heroin seeking during tests of reinstatement induced by foot shock stress and by heroin primes (0.25 mg/kg), as well as HPA hormonal responses to foot shock. We found that AVP mRNA levels were increased during early spontaneous withdrawal in the amygdala only. This amygdalar AVP mRNA increase was no longer observed at the later stage of heroin withdrawal. Foot shock stress increased AVP mRNA levels in the amygdala of rats withdrawn from heroin self-administration, but not in heroin naïve rats. Behaviorally, SSR149415 dose-dependently attenuated foot shock-induced reinstatement and blocked heroin-induced reinstatement. Finally, SSR149415 blunted the HPA activation by foot shock. Together, these data in rats suggest that stress responsive AVP/V1b receptor systems (including the amygdala) may be critical components of the neural circuitry underlying the aversive emotional consequences of drug withdrawal, as well as the effect of negative emotional states on drug-seeking behavior.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Corticosterone; Exploratory Behavior; Heroin; Heroin Dependence; Male; Rats; Rats, Inbred F344; Receptors, Vasopressin; RNA, Messenger; Substance Withdrawal Syndrome

Previous studies show that the acute administration of N-acetylcysteine (NAC) inhibits the desire for cocaine in addicts and cocaine-seeking in animals.. Rats were trained to self-administer heroin, and the reinstatement model of drug seeking was used to determine whether chronic NAC treatment inhibited heroin-seeking.. Daily NAC administration inhibited cue- and heroin-induced seeking. Moreover, repeated NAC administration during extinction training reduced extinction-responding and inhibited cue- and heroin-induced reinstatement for up to 40 days after discontinuing daily NAC injection.. These data show that daily NAC inhibits heroin-induced reinstatement and produces an enduring reduction in cue- and heroin-induced drug seeking for over 1 month after the last injection of NAC. Both the inhibitory effect of NAC on the reinstatement of heroin-seeking and the ability of NAC to reduce extinction-responding support clinical evaluation of repeated NAC administration to decrease in drug-seeking in heroin addicts.

Topics: Acetylcysteine; Animals; Behavior, Animal; Cues; Disease Models, Animal; Drug Interactions; Extinction, Psychological; Free Radical Scavengers; Heroin; Heroin Dependence; Male; Narcotics; Rats; Rats, Sprague-Dawley; Time Factors

This paper uses Australian heroin seizure data, along with estimates of the size of the Australian heroin market to evaluate the impact of drug law enforcement on the 2001 Australian heroin shortage from the percentage of the market seized. It also critically examines international heroin production trends and published reports on the causes of the Australian heroin shortage. Its conclusion is that previous studies may have overstated the success of drug law enforcement and that the most likely explanation for Australia's 2001 heroin shortage was a significant decline in heroin production world-wide, due to a general move away from heroin production in the countries of Southeast Asia and the prohibition on opium growing by the Taliban regime in Afghanistan.

Topics: Australia; Heroin; Heroin Dependence; Humans; Law Enforcement; Narcotics

Environmental drug-related cues have been implicated as a cause of illicit heroin use during methadone maintenance treatment of heroin dependence. The authors sought to identify the functional neuroanatomy of the brain response to visual heroin-related stimuli in methadone maintenance patients.. Event-related functional magnetic resonance imaging was used to compare brain responses to heroin-related stimuli and matched neutral stimuli in 25 patients in methadone maintenance treatment. Patients were studied before and after administration of their regular daily methadone dose.. The heightened responses to heroin-related stimuli in the insula, amygdala, and hippocampal complex, but not the orbitofrontal and ventral anterior cingulate cortices, were acutely reduced after administration of the daily methadone dose.. The medial prefrontal cortex and the extended limbic system in methadone maintenance patients with a history of heroin dependence remains responsive to salient drug cues, which suggests a continued vulnerability to relapse. Vulnerability may be highest at the end of the 24-hour interdose interval.

Topics: Acute Disease; Adult; Analgesics, Opioid; Behavior, Addictive; Brain; Cues; Dose-Response Relationship, Drug; Female; Frontal Lobe; Functional Laterality; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Methadone; Oxygen; Secondary Prevention; Visual Perception

As with other drugs of abuse, heroin use is characterized by a high incidence of relapse following detoxification that can be triggered by exposure to conditioned stimuli previously associated with drug availability. Recent findings suggest that cannabinoid CB(1) receptors modulate the motivational properties of heroin-conditioned stimuli that induce relapse behavior. However, the neural substrates through which CB(1) receptors modulate cue-induced heroin seeking have not been elucidated. In this study, we evaluated alterations in cue-induced reinstatement of heroin-seeking behavior produced by infusions of the CB(1) receptor antagonist SR 141716A (0, 0.3 and 3 microg per side) delivered into the prefrontal cortex (PFC), nucleus accumbens (NAC), and basolateral amygdala (BLA) of rats. Results show that following extinction of operant behavior the presentation of a discriminative stimulus conditioned to heroin availability reinstated nonreinforced lever pressing to levels comparable to preextinction levels. Intra-PFC SR 141716A dose-dependently reduced cue-induced reinstatement of heroin seeking, with a significant reduction following the 3 microg per side dose. In the NAC, both SR 141716A doses induced a significant reduction in cue-induced reinstatement, with the highest dose completely blocking the effect of the cue. In contrast, intra-BLA SR 141716A did not alter cue-induced reinstatement of responding while systemic administration of this antagonist (3 mg/kg, i.p.) significantly blocked cue-induced reinstatement in all three-placement groups (BLA, PFC, and NAC). These findings provide new insights into the neural mechanisms through which CB(1) receptors modulate the motivational properties of heroin-associated cues inducing relapse.

Topics: Amygdala; Animals; Conditioning, Operant; Cues; Disease Models, Animal; Dose-Response Relationship, Drug; Extinction, Psychological; Heroin; Heroin Dependence; Male; Motivation; Narcotics; Nucleus Accumbens; Piperidines; Prefrontal Cortex; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Reinforcement, Psychology; Reward; Rimonabant

Topics: Crime; Drug Prescriptions; Europe; Heroin; Heroin Dependence; History, 20th Century; History, 21st Century; Humans; Narcotics; Treatment Outcome

Topics: Drug Prescriptions; Heroin; Heroin Dependence; Humans; Narcotics

Topics: Drug Prescriptions; Heroin; Heroin Dependence; Humans; Narcotics; Risk Factors

We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.

Topics: Adult; Brain; Cerebrovascular Circulation; Euphoria; Heroin; Heroin Dependence; Humans; Image Processing, Computer-Assisted; Injections, Intravenous; Linear Models; Male; Models, Statistical; Narcotics; Oxygen; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Drug Prescriptions; Heroin; Heroin Dependence; Humans; Narcotics

Topics: Heroin; Heroin Dependence; Humans; Legislation, Drug; Narcotics

Topics: Drug Prescriptions; Heroin; Heroin Dependence; Humans; Narcotics

Topics: Acute Disease; Adult; Esotropia; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male

Long-term changes in glutamate transmission in the nucleus accumbens core (NAcore) contribute to the reinstatement of drug seeking after extinction of cocaine self-administration. Whether similar adaptations in glutamate transmission occur during heroin and cue-induced reinstatement of heroin seeking is unknown. After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training, heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions. Microdialysis was conducted in the NAcore during reinstatement of heroin seeking in animals extinguished from heroin self-administration or in subjects receiving parallel (yoked) noncontingent saline or heroin. Reinstatement by either heroin or cue increased extracellular glutamate in the NAcore in the self-administration group, but no increase was elicited during heroin-induced reinstatement in the yoked control groups. The increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NAcore with tetrodotoxin or by inhibiting glutamatergic afferents to the NAcore from the prelimbic cortex. Supporting critical involvement of glutamate release, heroin seeking induced by cue or heroin was blocked by inhibiting AMPA/kainate glutamate receptors in the NAcore. Interestingly, although a heroin-priming injection increased dopamine equally in animals trained to self-administer heroin and in yoked-saline subjects, inhibition of dopamine receptors in the NAcore also blocked heroin- and cue-induced drug seeking. Together, these findings show that recruitment of the glutamatergic projection from the prelimbic cortex to NAcore is necessary to initiate the reinstatement of heroin seeking.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Analysis of Variance; Animals; Behavior, Addictive; Behavior, Animal; Conditioning, Operant; Cues; Dopamine Antagonists; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glutamic Acid; Heroin; Heroin Dependence; Male; Narcotics; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Self Administration

Drugs are known to be a cause of pulmonary eosinophilia and several case reports of acute eosinophilic pneumonia associated with the use of cocaine have been reported. The changing pattern of heroin use, with a shift from intravenous use to smoking/inhalation of the substance, may lead to increased prevalence of heroin-induced pulmonary eosinophilia. We report on a case of a patient who had been inhaling heroin for about ten years. He presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed unilateral pleural effusion with segmental atelectasis. Examination of pleuritic fluid aspirate and bronchoalveolar lavage fluid revealed significant eosinophilia. He was diagnosed with acute eosinophilic pneumonia. Rapid remission was achieved after heroin abstinence and initiation of corticosteroid treatment.

Topics: Administration, Inhalation; Adult; Bronchoalveolar Lavage Fluid; Eosinophils; Heroin; Heroin Dependence; Humans; Leukocyte Count; Male; Narcotics; Pulmonary Eosinophilia; Tomography, X-Ray Computed

Topics: Australia; Heroin; Heroin Dependence; Humans; Law Enforcement; Narcotics

Topics: Australia; British Columbia; Heroin; Heroin Dependence; Humans; Law Enforcement; Narcotics; Needle-Exchange Programs; Substance Abuse, Intravenous; Time Factors

The circumstances of drug taking are thought to play a role in drug abuse but the evidence of it is anecdotal. Previous studies have shown that the intravenous self-administration of cocaine is facilitated in rats non-residing in the test chambers relative to rats that live in the test chambers at all times. We investigated here whether environmental context could exert its modulatory influence on heroin and amphetamine self-administration as well.. Independent groups of rats were given the possibility to self-administer different doses of heroin or amphetamine (12.5, 25.0, or 50.0 microg/kg). Some animals were housed in the self-administration chambers (resident groups) whereas other rats were transported to the self-administration chambers only for the test sessions (non-resident groups).. Amphetamine-reinforcing effects were more pronounced in non-resident rats than in resident rats, as previously reported for cocaine. Quite unexpectedly, the opposite was found for heroin. Because of this surprising dissociation, some of the rats trained to self-administer amphetamine were later given the opportunity to self-administer heroin. Also in this case, resident rats took more heroin than non-resident rats.. These findings suggest an unforeseen dissociation between opioid and psychostimulant reward and demonstrate that even in the laboratory rat some contexts are associated with the propensity to self-administer more opioid than psychostimulant drugs and vice versa, thus indicating that drug taking is influenced not only by economical or cultural factors but also can be modulated at a much more basic level by the setting in which drugs are experienced.

Topics: Amphetamine; Amphetamine-Related Disorders; Animals; Central Nervous System Stimulants; Conditioning, Operant; Dose-Response Relationship, Drug; Drug Interactions; Environment; Heroin; Heroin Dependence; Male; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Self Administration

In the accompanying paper, we described incubation of heroin-seeking behavior in rats following 14 days of abstinence. To gain an understanding of genomic changes that accompany this behavioral observation, we measured the expression of genes previously reported to respond to drugs of abuse. Specifically, after 1 or 14 days of abstinence, mRNA expression was measured for 11 genes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) immediately following a single 90 min extinction session. Additionally, the role of contingency was examined in control rats that received yoked, response-independent heroin administration. Gene expression was quantified by real-time quantitative PCR. Expression of five genes (Arc, EGR1, EGR2, Fos, and Homer1b/c) was changed in the mPFC. EGR1 and EGR2 expression was increased following the 90 min extinction session in a contingency-specific manner and this increase persisted through the 14 days of abstinence. Fos expression was also increased after 1 and 14 days of abstinence, but at 14 days this increase was response-independent (i.e., it occurred in both the rats with a history of heroin self-administration and in the yoked controls). Arc expression increased following the extinction session only in rats with a history of heroin self-administration and only when tested following 1, but not 14, days of abstinence. Homer 1 b/c decreased after 14 days of enforced abstinence in rats that received non-contingent heroin. Expression of only a single gene (EGR2) was increased in the NAc. These data demonstrate that behavioral incubation is coincident with altered levels of specific transcripts and that this response is contingently-specific. Moreover, EGR1 and EGR2 are specifically upregulated in self-administering rats following extinction and this finding persists through 14 days of abstinence, suggesting that these genes are particularly associated with the incubation phenomenon. These latter observations of persistent changes in gene expression following abstinence may reflect molecular correlates of relapse liability.

Topics: Animals; Behavior, Animal; Body Weight; Central Nervous System; Cues; Drinking; Extinction, Psychological; Gene Expression; Heroin; Heroin Dependence; Male; Narcotics; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA; Substance Withdrawal Syndrome

This study used heroin self-administration to investigate incubation of goal-directed heroin-seeking behavior following abstinence. Male Sprague-Dawley rats self-administered heroin on a fixed ratio 10 (FR10) schedule of reinforcement with licking of an empty spout serving as the operant behavior during 14 daily 3 h sessions. After this acquisition period, all rats received a 90 min extinction session following either 1 day or 14 days of home cage abstinence. When the extinction session occurred after only 1 day of home cage abstinence, rats with a history of heroin self-administration divided their responses equally between the previously "active" and "inactive" spouts. However, when the extinction session occurred following 14 days of home cage abstinence, the rats exhibited marked goal-directed heroin-seeking behavior by licking more on the previously "active" than "inactive" spout. These findings demonstrate that heroin-seeking behavior incubates over time, resulting in goal-directed heroin-seeking behavior in rats following 14 days but not 1 day of abstinence. Moreover, this facilitatory effect occurred in response to a different training schedule, lower total drug intake, and shorter periods of daily access than previously reported with heroin.

Topics: Animals; Conditioning, Operant; Extinction, Psychological; Goals; Heroin; Heroin Dependence; Male; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Self Administration; Substance Withdrawal Syndrome; Water Deprivation

These studies were designed to explore a peculiar behavior displayed by rats during the acquisition of heroin self-administration (0.05 mg/kg/infusion) on a fixed-ratio 1 schedule of reinforcement in limited access conditions (i.e. 3 h/day). Rats trained under these conditions develop a tendency to emit extra lever presses during the time of heroin infusions (unreinforced responses). We found that a similar behavior develops in animals responding for sucrose pellets, but not for intravenous infusions of cocaine (0.5 mg/kg/infusion, 3 h/day). In sucrose trained rats, unreinforced responses emitted during the delivery of sucrose pellets was enhanced by food deprivation. In heroin trained rats, development of unreinforced responding was accompanied by an increase in responding for heroin on a progressive ratio schedule, and by a reduction of the depressant action of heroin (3 mg/kg, SC) on locomotor activity. On the basis of these findings, we concluded that unreinforced responding during heroin self-administration reflects a change in the motivation to obtain the drug, as well as a reduced sensitivity the motor impairing action of heroin. This suggests that acquisition of heroin self-administration is regulated by a balance between drug effects that promote and limit heroin intake.

Topics: Animals; Cocaine; Conditioning, Operant; Dopamine Uptake Inhibitors; Food Deprivation; Heroin; Heroin Dependence; Injections, Intravenous; Male; Motivation; Motor Activity; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Self Administration; Sucrose

Topics: Australia; Heroin; Heroin Dependence; Humans; Law Enforcement; Narcotics; Time Factors

A group of 15 chronic opioid addicts (DA) with mean age 26.5+/-7.3 years was studied by means of a rotational Contraves Low Shear 30 viscometer and the results have been compared with a control group of 19 healthy subjects. It was found that the mean whole blood viscosity values of the investigated group of heroin abusers (n=15) were elevated compared to that of healthy persons (n=19) over the whole shear rate range and fell by more than ten orders of magnitude (Savov et al., 2006). The present investigation uses the coefficients of the models of Ostwald-de-Walle (power law) and Herschel-Bulkley law, which describe whole blood flow curves (tau-gamma) within the shear rates range from 10(-2) to 10(2) s(-1) and itself incorporate whole blood viscosity data in the entire shear rate range. A significant difference in the mean yield shear stress tau(0) values of the drug abusers' group compared to the controls was found. A strong positive linear correlation was determined between the parameters of RBC aggregation in the group of heroin addicts confirming our previous results (Ivanov and Antonova, 2005; Savov, Zvetkova et al., 2007; Savov, Antonova et al., 2007) for intensive RBC and platelet aggregation and morphological changes in DA group.

Topics: Adult; Blood Viscosity; Erythrocyte Aggregation; Erythrocyte Deformability; Erythrocyte Indices; Erythrocytes; Female; Hematocrit; Hemorheology; Heroin; Heroin Dependence; Humans; Male; Regression Analysis; Rheology

In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine. Victims of lethal heroin overdose often present with fairly low blood concentrations of morphine. Reduced tolerance due to abstinence has been proposed to account for this finding. The aim of the present study was to examine the role of abstinence in drug-related deaths by comparing recent and past exposure to opioids using segmental hair analysis with the postmortem blood morphine concentrations in deceased heroin users. The study included 60 deceased drug addicts in the Stockholm area, Sweden. In 32 cases, death was not related to heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most recent hair segment, suggesting a reduced tolerance to opioids. However, the blood morphine levels were similar to those found in the 10 subjects that showed continuous opioid use. Hair and blood analysis disclosed an extensive use of additional drugs that directly or indirectly may influence the opioid system. The results suggest that abstinence is not a critical factor for heroin overdose death. Obviously tolerant subjects die after intake of similar doses. Other factors, particularly polydrug use, seem to be more causally important for these deaths.

Topics: Adult; Aged; Drug Overdose; Drug Tolerance; Female; Forensic Pathology; Hair; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Morphine

Methadone maintenance therapy has been the mainstay of treatment for heroin addiction since the 1970s. Recent studies indicate that methadone is of greater relative intrinsic efficacy than the active metabolites of heroin at mu-opioid receptors and that the extent of mu-opioid receptor desensitization is dependent upon agonist efficacy. Regional differences have been found for mu-opioid receptor desensitization with chronic heroin self-administration, and a similar paradigm was employed to compare regional differences between the effects of heroin and methadone. Rats were trained to self-administer heroin i.v., and the dose available was increased incrementally to a terminal value of 6 mg/kg for each infusion. Half of these rats were allowed to continue to self-administer heroin, while dependence was maintained in the others by hourly infusions of 3 mg/kg of methadone. A separate group of animals was kept on a low dose of heroin. Activation of G-proteins by the high efficacy agonist DAMGO was decreased to a greater extent in animals treated chronically with methadone compared with those allowed to self-administer heroin in amygdala, periaqueductal gray, and subicular nucleus. Activation of G-proteins by the partial agonist endomorphin was decreased in striatum, thalamus, and amygdala in rats from all drug treatment groups, but to a greater extent in the striatum in methadone treated rats compared with the heroin groups. Elucidating the mechanisms by which methadone induces differential desensitization of mu-opioid receptors across brain regions compared with heroin could provide insights to improve the pharmacotherapy of heroin addiction.

Topics: Animals; Binding, Competitive; Brain; Dose-Response Relationship, Drug; Drug Tolerance; Eating; Guanosine 5'-O-(3-Thiotriphosphate); Heroin; Heroin Dependence; Injections, Intravenous; Male; Methadone; Narcotics; Radioligand Assay; Rats; Rats, Inbred F344; Receptors, G-Protein-Coupled; Receptors, Opioid, mu; Reinforcement, Psychology; Self Administration

Genetic factors that influence subjective responses to drug use (such as euphoria) contribute to the risk of addiction. mu-opioid receptor is the molecular target of heroin mediating its effects in both pain relief and euphoria.. To evaluate the association of mu-opioid receptor gene (OPRM1) variants with heroin-induced positive responses on first use, we studied 336 Chinese Han heroin addicts recruited in Shanghai and divided heroin addicts into two groups (positive vs. negative) according to the self-reporting feeling on first use. Association analyses with the genotypes and alleles in nine tagging single nucleotide polymorphisms (tSNPs) in OPRM1 with subjective responses were performed. Similar analysis with haplotypes of these tSNPs was also performed.. Allele frequencies of three tSNPs were significantly different between the positive and negative groups. They were rs696522 (odds ratio [OR] = 3.06, p = .0013), rs1381376 (OR = 3.16, p = .0008), and rs3778151 (OR = 3.12, p = .0004). Such association remains after adjustment for demographic covariates and for multiple testing. The subjects with heroin-induced positive responses on first use consumed more drugs than the negative group (Mann-Whitney U = 224.0, Wilcoxon W = 16334.0, p

Topics: Adult; China; Exons; Female; Genotype; Heroin; Heroin Dependence; Humans; Linkage Disequilibrium; Logistic Models; Male; Narcotics; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Receptors, Opioid, mu; Reverse Transcriptase Polymerase Chain Reaction; Surveys and Questionnaires

The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hour later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate that cholinergic transmission influences heroin self-administration and reinstatement. Moreover, cue-induced reinstatement was inhibited by physostigmine in the NAc and potentiated by cholinergic stimulation in the VTA.

Topics: Acetylcholine; Animals; Cholinergic Fibers; Cholinesterase Inhibitors; Conditioning, Operant; Cues; Dose-Response Relationship, Drug; Exploratory Behavior; Heroin; Heroin Dependence; Learning; Male; Microinjections; Muscarinic Antagonists; Narcotics; Neural Pathways; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Reward; Self Administration; Synaptic Transmission; Ventral Tegmental Area

We present the case of a 21-year-old female drug addict with severe accidental hypothermia (core body temperature 27.5 degrees C) and cardiorespiratory arrest. After successful cardiopulmonary resuscitation the patient was actively internally rewarmed without the use of extracorporal circulation. Although at the first clinical presentation the patient appeared to be dead, an excellent neurological outcome was achieved. This case report reviews the epidemiology, pathophysiology, prognostic markers and the therapeutic approaches of severe hypothermia.

Topics: Adult; Analgesics, Opioid; Cardiopulmonary Resuscitation; Drug Overdose; Female; Heart Arrest; Heroin; Heroin Dependence; Humans; Hypothermia; Prognosis; Rewarming

The aim of this study was to determine predictors of non-fatal overdose (OD) among a cohort of 470 adults after detoxification from heroin, cocaine or alcohol.. We examined factors associated with time to OD during 2 years after discharge from an urban detoxification unit in Boston, MA, USA using multivariable regression analyses. Separate analyses were performed for both the total sample and a subgroup with problem opioid use.. Lifetime prevalence for any OD was 30.9% (145/470) in the total sample and 42.3% (85/201) in patients with opioid problems. During the 2-year follow-up, OD was estimated to occur in 16.9% of the total sample and 26.7% of the opioid problem subgroup, with new-onset (incidence) OD estimated at 5.7% and 11.0%, respectively. Factors associated with an increased hazard of OD in both samples included white race, more depressive symptoms, and prior OD regardless of intent. Prior suicidal ideation or attempt was not associated with future OD.. Findings underscore both the high prevalence of non-fatal OD among detoxification patients especially opioid users, and the potency of prior OD as a risk factor for future OD. Depressive symptoms, a modifiable risk factor, may represent a potential intervention target to prevent OD, including some "unintentional" ODs.

Topics: Adult; Alcoholism; Boston; Cocaine; Cocaine-Related Disorders; Comorbidity; Cross-Sectional Studies; Depression; Drug Overdose; Ethanol; Female; Heroin; Heroin Dependence; Humans; Male; Proportional Hazards Models; Prospective Studies; Risk Factors; Urban Population

Topics: Acute Disease; Adult; Basal Ganglia; Basal Ganglia Diseases; Female; Heroin; Heroin Dependence; Humans; Parkinson Disease, Secondary

In early 2001, Australia experienced a sudden and dramatic reduction in the availability of heroin. Research examining the impact of the reduction on drug-related harms has yielded a conflicting picture. The current study uses data from a prospective cohort study of anti-HCV negative injecting drug users (IDU) (n=368) to examine patterns of injecting drug use, risk behaviours and HCV incidence before and after the reduction. The proportion of participants mainly injecting heroin declined sharply from 74% to 47% after the onset of the reduction and continued throughout 2001. There was marked shift to other drugs, mainly cocaine and amphetamine. Cocaine injectors had the highest risk profile and the highest incidence of HCV (82.6 per 100 person years, 95% CI 52.0-131.0). While HCV seroconversions increased by year, this increase was not statistically significant. We observed a reduction in heroin injection and a concomitant increase in cocaine injection and a significant association between cocaine injection and incident HCV infection during a period of reduced heroin availability. Results suggest that attempts to suppress drug markets by manipulating availability may result in collateral damage in the form of drug-related harms, indicating a need for more sophisticated understandings of the potential trade-offs involved in attempting to suppress the supply of illicit drugs.

Topics: Amphetamine-Related Disorders; Cocaine-Related Disorders; Cohort Studies; Cross-Sectional Studies; Hepatitis C; Heroin; Heroin Dependence; Humans; Incidence; Needle Sharing; New South Wales; Prospective Studies; Risk-Taking; Statistics as Topic; Substance Abuse Detection; Substance Abuse, Intravenous

Buprenorphine has been approved for heroin detoxification, but little is known about its impact on everyday practice. Concerns about buprenorphine include expense, limited knowledge about its use, patient limits, and social and clinical attitudes regarding opioid treatment for heroin dependence. On the other hand, randomized clinical trials suggest that buprenorphine is superior to clonidine with regard to withdrawal symptom relief. In June 2004, a community-based residential medical detoxification center switched from clonidine to buprenorphine treatment for all new and returning heroin clients. This study is a retrospective chart review of subject outcomes with clonidine (n = 100) versus buprenorphine (n = 100). Bivariate analysis suggested few cohort differences in pretreatment demographics and client characteristics. In contrast, buprenorphine was significantly associated with increased length of stay and treatment completion. The positive associations between buprenorphine and both treatment completion and length of stay persisted and were slightly enhanced after regression analysis adjusted for potential confounders. Additionally, clinical staff reported better subject engagement in treatment and psychosocial group sessions. This single-site study is an example of successful integration of an evidence-based treatment into community-based practice.

Topics: Acute Disease; Adult; Buprenorphine; Clonidine; Diffusion of Innovation; Female; Heroin; Heroin Dependence; Humans; Length of Stay; Male; Middle Aged; Narcotics; Oregon; Patient Acceptance of Health Care; Retrospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

Prescription opioid dependence is increasing, but treatment outcomes with office-based buprenorphine/naloxone among these patients have not been described.. We compared demographic, clinical characteristics and treatment outcomes among 200 patients evaluated for entry into a trial of primary care office-based buprenorphine/naloxone treatment stratifying on those who reported exclusive heroin use (n = 124), heroin and prescription opioid use (n = 47), or only prescription opioid use (n = 29).. Compared to heroin-only patients, prescription-opioid-only patients were younger, had fewer years of opioid use, and less drug treatment history. They were also more likely to be white, earned more income, and were less likely to have Hepatitis C antibodies. Prescription-opioid-only patients were more likely to complete treatment (59% vs. 30%), remained in treatment longer (21.0 vs. 14.2 weeks), and had a higher percent of opioid-negative urine samples than heroin only patients (56.3% vs. 39.8%), all p values < .05. Patients who used both heroin and prescription opioids had outcomes that were intermediate between heroin-only and prescription-opioid-only patients.. Individuals dependent on prescription opioids have an improved treatment response to buprenorphine/naloxone maintenance in an office-based setting compared to those who exclusively or episodically use heroin.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Office Visits; Opioid-Related Disorders; Primary Health Care

Research on the neurocognitive characteristics of heroin addiction is sparse and studies that do exist include polydrug abusers; thus, they are unable to distinguish neurocognitive effects of heroin from those of other drugs. To identify neurocognitive correlates specific to heroin addiction, the present study was conducted in St. Petersburg, Russia where individuals typically abuse and/or become addicted to only one substance, generally alcohol or heroin. Heroin addicts were recruited from an inpatient treatment facility in St. Petersburg. Three comparison groups included alcoholics, addicts who used both alcohol and heroin, and non-abusers. Psychiatric, background, and drug history evaluations were administered after detoxification to screen for exclusion criteria and characterize the sample. Executive Cognitive Functions (ECF) that largely activate areas of the prefrontal cortex and its circuitry measured include complex visual pattern recognition (Paired Associates Learning), working memory (Delayed Matching to Sample), problem solving (Stockings of Cambridge), executive decision making (Cambridge Decision Making Task), cognitive flexibility (Stroop Color-Word Task) and response shifting (Stop Change Task). In many respects, the heroin addicts were similar to alcohol and alcohol+heroin dependent groups in neurocognitive deficits relative to controls. The primary finding was that heroin addicts exhibited significantly more disadvantageous decision making and longer deliberation times while making risky decisions than the other groups. Because the nature and degree of recovery from drug abuse are likely a function of the type or pattern of neurocognitive impairment, differential drug effects must be considered.

Topics: Adolescent; Adult; Alcohol-Related Disorders; Alcoholic Beverages; Brain; Comorbidity; Cross-Sectional Studies; Decision Making; Female; Heroin; Heroin Dependence; Humans; Male; Neuropsychological Tests; Neurotoxicity Syndromes; Problem Solving; Russia; Substance Abuse Treatment Centers

Previous studies have demonstrated an interaction between opioids and noncompetitive antagonists at N-methyl-D: -aspartate (NMDA) receptors, but few studies have examined the utility of these medications for treating opioid dependence.. In this 8-week inpatient study, participants were maintained on the low-affinity, noncompetitive NMDA receptor antagonist memantine (0, 30, and 60 mg per day, PO) and under each maintenance dose condition, the effects of intranasal heroin (0, 12.5, and 50 mg, IN) were examined.. During the first week after admission to the hospital, participants were detoxified from heroin. All of the volunteers received all of the memantine and heroin dose combinations. Participants (N = 8) first sampled a dose of heroin and $20. During a subsequent choice session, participants could self-administer heroin and/or money. Responses, which consisted of finger presses on a computer mouse, were made under a modified progressive ratio schedule (PR 50, 100, 200, 400, 800, 1,200, 1,600, 2,000, 2,400, and 2,800) during a ten-trial self-administration task. Subjective, performance, and physiological effects were measured repeatedly during laboratory sessions.. Memantine produced modest reductions in subjective ratings of drug quality, liking, willingness to pay for the drug, and craving for heroin. However, memantine produced few changes in the reinforcing effects of heroin.. These data demonstrate that memantine was well tolerated and modestly effective in reducing the subjective but not the reinforcing effects of heroin. Although it is unlikely that memantine will be useful as a stand-alone maintenance medication for opioid dependence, it may have some utility as an adjunct treatment medication.

Topics: Administration, Intranasal; Adult; Behavior, Addictive; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Female; Heroin; Heroin Dependence; Humans; Male; Memantine; Motivation; Narcotics; Receptors, N-Methyl-D-Aspartate; Reinforcement, Psychology; Self Administration

Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The purpose of the present study was to examine the effect of the administration of naltrexone on craving level after rapid opioid detoxification induced by naltrexone. A naturalistic study was carried out in which patients were followed during 10 months after rapid detoxification. Data about abstinence, relapse, and naltrexone use were collected by means of urine specimens. Craving was measured by the visual analogue scale craving, the Obsessive Compulsive Drug Use Scale, and the Desires for Drug Questionnaire. Results showed that patients who relapsed in opioid use experienced obviously more craving than abstinent people. Patients who took naltrexone did not experience significant less craving than those who did not. These results suggest that the use of opioids is associated with increased craving and that abstinence for opioids is associated with less craving, independent of the use of naltrexone. This is in contrast to the general opinion. Because of the naturalistic design of the study, no firm conclusions can be drawn, but the results grounded the needs of an experimental study.

Topics: Adult; Female; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Middle Aged; Motivation; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Secondary Prevention; Substance Abuse Detection; Substance Withdrawal Syndrome; Surveys and Questionnaires

The use of illicit heroin is associated with aberrant neurology of unknown aetiology and various psychiatric illnesses. Aluminium, which is a proven neurotoxin, is present in significant amounts in illicit heroin and may also be volatilized and inhaled following the vaporization of heroin off aluminium foil ('Chasing the Dragon'). The purpose of this study was to establish if the use of illicit heroin was associated with an increase in the body burden of aluminium. We have used graphite furnace atomic absorption spectrometry to measure the aluminium and iron contents of the urine of current and past users of illicit heroin and used these data to estimate body burdens of aluminium. Urinary excretion of aluminium is the most effective non-invasive indicator of the body burden of aluminium and was found to be significantly (P < 0.001) higher in users of illicit heroin, range 14-3382 nmol/mmol creatinine (mean +/- SD; 222 +/- 491 nmol/mmol creatinine), than in a normal non-drug abusing control population, range 23-74 nmol/mmol creatinine (mean +/- SD; 43 +/- 19 nmol/mmol creatinine). Exposure to aluminium from the use of illicit heroin may be of particular significance because the urinary excretion of iron, another major contaminant of illicit heroin, in users (mean +/- SD; 53 +/- 63 nmol/mmol creatinine) was not significantly different (P > 0.05) from the control population (mean +/- SD; 38 +/- 18 nmol/mmol creatinine). We have shown for the first time that the use of illicit heroin may be a significant contributor to the body burden of aluminium. Further research will be required to determine if adventitious aluminium has a role in heroin use-related neuropathology and neurology.

Topics: Adult; Aluminum; Body Burden; Creatinine; Drug Contamination; England; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Spectrophotometry, Atomic

The detection of markers for illicit opiate misuse is important both in the management of substance misuse and in the postmortem identification of illicit opiate use. In addition to 6-monoacetylmorphine and acetyl codeine, other markers, such as papaverine, noscapine, and their metabolites, have been proposed as markers of illicit opiate use. Urine samples (362) from individuals attending substance misuse services and 26 postmortem cases were analyzed for meconin, a noscapine metabolite by gas chromatography-mass spectrometry. Three hundred of the substance misuse service samples and 14 of the postmortem samples had morphine present as the major opiate. Meconin was detected in 284 (94.7%) of these substance misuse samples and 11 (78%) of the postmortem samples. There was a specificity of 100% in both groups. In the 62 substance misuse cases where morphine was not the major opiate detected and four separate cases in which medicinal diamorphine was known to have been administered, meconin was not detected. The use of meconin as a useful adjunct in detecting illicit opiate use is recommended.

Topics: Biomarkers; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Illicit Drugs; Noscapine; Sensitivity and Specificity; Substance Abuse Detection

This paper describes injection risk in an out-of-treatment population of young heroin users in Hanoi, Vietnam, including use of a soft-tissue portal known as a "cay ma" (injection sac).. Data from a large cross-sectional survey (N=1270) are used to describe the prevalence of this practice and its association with disease. Additionally, data from an ethnographic substudy on injectors serve to elaborate injectors' rationales for this injection practice.. This practice was common in this sample, appearing soon after initiation of habitual injection. Injectors report that this allows rapid and reliable access to a vein; strategic advantages in a dense urban environment where rapid injection, typically in public settings, is necessary to avoid discovery or arrest. Additionally, this practice is believed to mitigate risk for vein damage from co-morbid promethazine hydrochloride injection.. This practice may draw lymphocytes to injection sites, thereby increasing risk for transmission of bloodborne pathogens. Structural and behavioral interventions are needed for young heroin users in Vietnam.

Topics: Adolescent; Adult; Anthropology, Cultural; Blood-Borne Pathogens; Cross-Sectional Studies; Female; Health Surveys; Hepatitis B; Heroin; Heroin Dependence; HIV Infections; Humans; Injections, Subcutaneous; Male; Narcotics; Pneumonia; Substance Abuse, Intravenous; Vietnam

In the UK, few doctors prescribe diamorphine for the treatment of opiate dependence to a small number of patients. A retrospective case note review of patients receiving diamorphine in 2000 was conducted in the UK to determine how and why these patients came to receive a prescription for diamorphine. Patient eligibility criteria were examined together with doctors' stated reasons for initiating a diamorphine (heroin) prescription. Two hundred and ten sets of patients' case notes were reviewed at 27 of the 42 (64%) drug clinics in England and Wales where diamorphine was prescribed by the doctor. There appeared to be a general consensus among the few doctors who had prescribed diamorphine that it was a treatment of last resort, for those with long histories of heroin use and injecting, and those who had not responded sufficiently well to previous other treatments. However, there was also a small number of patients initiated on diamorphine without ever having previously received opiate treatments and some because they were experiencing problems injecting methadone. This reflects the UK history of the individual doctor's clinical autonomy in deciding when diamorphine is appropriate and the previous lack of nationally agreed patient eligibility criteria.

Topics: Adolescent; Adult; Cocaine-Related Disorders; Crack Cocaine; Drug Administration Routes; Drug Prescriptions; England; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Retreatment; Retrospective Studies; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Treatment Failure; Wales

To investigate the effect of M(5) muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats.. Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M(5) muscarinic receptor was transferred with the lipofectin.. Microinjection of AS-ONs targeting M(5) muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocampus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M(5) muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M(5) muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats.. Blocking M(5) muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M(5) muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.

Topics: Acetylcholine; Animals; Brain; Heroin; Heroin Dependence; Hippocampus; Immunohistochemistry; Male; Microinjections; Motor Activity; Narcotics; Neural Pathways; Neurons; Nucleus Accumbens; Oligonucleotides, Antisense; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M5; Synaptic Transmission; Ventral Tegmental Area

Topics: Acute Disease; Administration, Inhalation; Adult; Asthma; Eosinophilia; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics

This study examines the quality of street heroin seized in Vienna in 1999 and whether there was a relationship between the purity of street heroin and the number of heroin-related emergencies as well as the number of heroin-related deaths. Street heroin confiscated by the Viennese police, run-sheets of drug-related emergencies, and postmortem reports of drug-related deaths in Vienna in 1999 were analyzed. A total of 415 retail samples with a total weight of 128.02 g contained a median percentage of 6.5% diacetylmorphine (range: 0.0-47.0%). All the samples contained a diluent, mainly lactose, as well as adulterants, such as caffeine and/or paracetamol. During the study period, 75 heroin-related deaths and 387 heroin-related emergencies were registered in Vienna. Time-series analysis revealed no statistically significant relationship between the rate of heroin-related incidents and the diacetylmorphine concentration of street heroin samples confiscated in Vienna in 1999. The widely held belief that the number of heroin-related deaths could be explained simply through fluctuations in the purity of street heroin could not be substantiated, even though the results of this study do not rule out an association between the purity of heroin and heroin-related deaths/emergencies.

Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Austria; Caffeine; Central Nervous System Stimulants; Drug Contamination; Emergencies; Female; Forensic Toxicology; Heroin; Heroin Dependence; Humans; Illicit Drugs; Lactose; Male; Narcotics; Sweetening Agents

To evaluate the prevalence of and risk factors for nonfatal overdose among heroin users in southwestern China.. In 2005, 731 heroin users in Sichuan Province, China were interviewed for overdose experiences in the past 12 months. Factors hypothesized to be associated with overdose were evaluated with logistic regression models.. Eighty-eight (12%) drug users experienced at least one overdose, with a range from 1 to 20; 45 (51%) experienced 2 or more overdoses. Over half of participants with experience of overdose were recently released from prison (52%), and 56% used benzodiazepines before overdose. Longer methadone treatment in the past year (>or=180 vs. 0 days; OR, .3; 95% CI, .1-.8; P = .02), longer duration of using drugs (>or=7 vs. <7 years; OR, 2.2; 95% CI, 1.3-3.6; P = .002), and more frequency of injecting drugs in the past 3 months (>or=7 vs. <7 times/week; OR, 5.4; 95% CI, 3.2-9.0; P < .001) were independently associated with increased risk of nonfatal heroin overdose.. Nonfatal heroin overdoses are common among Chinese heroin users. Drug users should be encouraged to participate and remain in methadone treatment to prevent overdose and be educated about proper response to overdose to reduce risk of overdose death.

Topics: Adult; Cause of Death; China; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Logistic Models; Male; Methadone; Multivariate Analysis; Prevalence; Risk Factors; Substance Abuse, Intravenous

Topics: Clenbuterol; Fentanyl; Heroin; Heroin Dependence; Humans; Illicit Drugs; Quinine; Scopolamine; Xylazine

This study compared the characteristics of intravenous (i.v.) and intranasal (i.n.) heroin users seeking methadone treatment, and their response to treatment.. A total of 319 heroin-dependent adults.. Participants were assigned randomly to receive interim methadone treatment or to a waiting list control on a 3 : 2 basis. Analyses were conducted by dividing participants into two groups based on their route of heroin ingestion: i.v. or i.n.. A methadone clinic in Baltimore City, Maryland.. Interim methadone treatment consisted of providing an adequate and stable dose of methadone, but no psychosocial services, to heroin-dependent adults for up to 120 days while they awaited an opening for comprehensive methadone treatment.. Addiction Severity Index, Texas Christian University AIDS Risk Assessment, a questionnaire on treatment entry and a urine drug test were collected at baseline and at entry into a comprehensive treatment program, or at 120 days after baseline assessment, whichever came first.. At baseline, over 60% of participants were i.n. users and had been for an average of over 12 years; i.v. users, compared to i.n. users, were more likely to have ever used cocaine, to have used cocaine in the past 30 days, to have more medical complications and to report more income generated from criminal behavior. Both i.v. and i.n. users reduced their self-reported days of heroin use, cocaine use and days of criminal activity in response to interim methadone treatment.. Despite differences in baseline characteristics, i.n. and i.v. heroin-dependent individuals did not differ in their response to interim methadone treatment.

Topics: Adult; Cocaine-Related Disorders; Drug Administration Schedule; Female; Heroin; Heroin Dependence; Humans; Male; Maryland; Methadone; Patient Acceptance of Health Care; Social Class; Substance Abuse Treatment Centers; Treatment Outcome

To compare the blood toxicology of heroin overdose cases and morphine positive homicide victims.. Analysis of coronial cases.. Sydney, Australia. Cases A total of 705 cases of death due to opioid toxicity and 28 morphine positive homicide cases (1 January 1998-31 December 2002).. There was no significant difference between the median morphine concentrations of the overdose and homicide groups (0.50 versus 0.45 mg/l). The overdose group was more likely to have blood alcohol (OR 3.21) present, but less likely to have methadone (OR 0.26) and cannabis (OR 0.04). There was a significant negative correlation between blood morphine and alcohol concentrations among the overdose group (rho = -0.32), but not among the homicide group (rho = -0.03). Independent predictors of a higher blood morphine concentration were a lower alcohol concentration and a higher methadone concentration.. Morphine concentrations per se are not diagnostic of overdose. The study confirms the salience of concomitant alcohol consumption in such events.

Topics: Adult; Cause of Death; Drug Overdose; Female; Forensic Medicine; Heroin; Heroin Dependence; Homicide; Humans; Male; Morphine; New South Wales; Substance Abuse, Intravenous

To investigate the effect of heroin on the immune function, growth and development in the teenager heroin addicts by measuring their T-lymphocyte subsets, Th1/Th2 cytokines and serum growth hormone.. Tlymphocyte subsets of peripheral blood from the teenager heroin addicts were measured by direct microvolume whole blood immunofluorescent staining technique by flow cytometer (FCM). Thl / Th2 cytokines were measured by BD cytometric bead array and serum growth hormone was assayed using the chemiluminescence method in the 20 teenager heroin addicts and 23 healthy teenagers.. The levels of CD3(+), CD3(+) + CD4(+), CD3(+) + CD4(+)/CD3(+)+ CD8(+), Th1 cytokines(IL-2, TNF-alpha and IFN-gamma) and Th2 cytokines(IL-4 and IL-10) reduced significantly in the teenager heroin addicts compared with the healthy control group (P < 0.01 or P < 0.05). The level of Th1 cytokines(IL-2 + TNF-alpha+IFN-gamma) decreased more than that of Th2 cytokines(IL-4 + IL-5 + IL-10)(P < 0.05). The level of serum growth hormone from the teenager heroin addicts was remarkably higher than that in control group (P<0.01).. Heroin can inhibit the immunofunction especially the celluar immunity of the teenager heroin addicts. Besides, it can increase the level of serum growth hormone of the teenager heroin addicts.

Topics: Adolescent; Antigens, CD; Case-Control Studies; Child; Cytokines; Female; Growth Hormone; Heroin; Heroin Dependence; Humans; Male; T-Lymphocyte Subsets; T-Lymphocytes; Th1 Cells; Th2 Cells

Nonfatal heroin overdoses and suicide attempts are both common among heroin addicts, but there is limited knowledge about the association between them. The sample in the present study consisted of 149 regular heroin users in Malmö, Sweden. Out of these 98 had taken an unintentional heroin overdose at some time and 51 had made at least one attempt to commit suicide (but not using heroin). Suicide attempts were significantly more common among those who had taken unintentional overdoses as compared with those who had never taken any overdose (p < 0.01). The more overdoses, the greater the risk of suicide attempt.

Topics: Adult; Comorbidity; Depressive Disorder; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Needle-Exchange Programs; Recurrence; Risk Factors; Substance Abuse Treatment Centers; Suicide, Attempted; Sweden

Topics: Carotid Artery, Internal, Dissection; Cerebral Angiography; Female; Heroin; Heroin Dependence; Humans; Injections, Intra-Arterial; Intracranial Aneurysm; Middle Aged; Neck; Subarachnoid Hemorrhage; Substance Abuse, Intravenous; Tomography, X-Ray Computed; Vertebral Artery; Vertebral Artery Dissection

A 43-year-old female was reported to inject heroin, which led to her rapid death. Because of the potential for criminal charges, laboratory results that could verify "hotshot" heroin overdose were valuable. Initial toxicological analysis detected morphine (0.78 mg/L), amitriptyline (2.91 mg/L), and nortriptyline (2.80 mg/L) in femoral blood. Because these tricyclic antidepressant levels alone might normally be associated with a fatal outcome, the ratio of free versus total morphine (88.6%) and presence of 6-monoacetylmorphine in vitreous fluid were used support a history of rapid death following intravenous (IV) administration. The distribution of amitriptyline and nortriptyline was consistent with accumulation of drug after chronic dosing. Our other results suggest that the low morphine level in vitreous humor fluid (0.16 mg/L) relative to free morphine in femoral blood (0.78 mg/L) may also be an indicator of limited survival time following exposure to morphine. Based upon comprehensive toxicologic analysis, we determined overdose due to IV abuse of heroin was likely to have precipitated the fatal outcome. This case underscores the need for complete toxicologic workup and to consider individual variation in the dose response during toxicologic interpretation of postmortem results.

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Drug Interactions; Drug Overdose; Fatal Outcome; Female; Forensic Toxicology; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Morphine; Morphine Derivatives; Nortriptyline

This study describes overdose experiences of heroin users, both the overdoses they themselves experienced, as well as those that they witnessed. A structured interview was performed with 101 current heroin users in Albuquerque, New Mexico from January 7, 2002 to February 26, 2002. Heroin-related overdoses were found to be common in this sample of heroin users. Three or more persons were reported to be present during 80 of the 95 most recently witnessed overdoses. An ambulance was called in only 42 of the 95 witnessed overdoses. Seventy-five percent of the respondents who witnessed an overdose stated concern over police involvement was an important reason for delay or absence of a 911 call for help. One hundred of the 101 respondents reported willingness, if trained, to use rescue breathing and to inject naloxone to aid an overdose victim. New methods need to be found to reduce heroin overdose death. Scientific studies are needed on the efficacy of take-home naloxone.

Topics: Adolescent; Adult; Attitude to Health; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pilot Projects

There have been recent calls from within both Scotland and England for the wider prescription of heroin to heroin addicts as a way of coping with our burgeoning drug problem and as a route to reducing drug related criminality. But how feasible is heroin prescribing in this context? This paper considers some of the existing research evidence relating to heroin prescribing and looks also at the ethics and practicalities of prescribing heroin to heroin addicts in Scotland. We conclude that whilst the evidence on the benefits of heroin prescribing is far from clear cut there is a case for mounting a Scottish trial of heroin prescribing. Such a trial would need to be tightly controlled and rigorously evaluated. It would need to show that heroin prescribing was associated not only with a comparable level of harm reduction, as methadone prescribing, but that it was also an effective route towards drug users' eventual recovery and drug cessation.

Topics: Attitude of Health Personnel; Heroin; Heroin Dependence; Humans; Practice Patterns, Physicians'; Scotland

Between about 1964 and 1969, drug consumption was embedded into the transnational networks of a countercultural youth underground. In London, the high mobility of the underground members was evoking a deep-rooted fear of a casual way of life. The West Berlin underground was much more politicized than its London counterpart. In West Berlin, until the last third of the 1970s, there was no coordinated anti-drug policy. This changed when the situation of heroin users deteriorated. Politicians as well as the members of the self-help organizations began to realize that a close cooperation and an improved communication were imperative. The situation for heroin users in 1970s London was not that bad when compared to Berlin because a relatively well-functioning civil society already existed, and there were special clinics, the Drug Treatment Centers, and a relatively well-working network of voluntary organizations.

Topics: Adolescent; Adolescent Behavior; Berlin; Cultural Characteristics; Drug Users; Government Programs; Health Promotion; Heroin; Heroin Dependence; History, 20th Century; Humans; Illicit Drugs; London; Public Health; Self-Help Groups; Social Behavior; Social Change; Substance Abuse Treatment Centers; Substance-Related Disorders

Prescribing of injectable diacetylmorphine (DAM) for heroin dependence has raised concerns about its safety. In light of various reports by heroin-maintained patients of DAM-related adverse events, and previously established unwanted effects of opioids in pain management, we undertook a survey in February 2001 of a random sample of 132 (127 participated) of 1061 patients prescribed DAM in Switzerland at that time. The purpose was to document the prevalence rates of a list of unintended symptoms experienced and attributed to DAM by patients. To assess symptom complaints and other data, staff administered a six-page self-report questionnaire. The patients ascribed numerous symptoms to DAM, with the best-known being the most frequently reported (e.g. skin itching, sweating, constipation). Among potentially more problematic complaints ranged irregular menses, cognitive deficits, muscle twitches, labored breathing, pains in the cardiac region, and temporary paralysis of limbs. In the absence of a control group, however, these may also be due to other factors, such as expectation, co-medication, concomitant substance use or co-morbidity. This pilot study emphasizes the necessity of rigorous assessment of the true rates, types, severity and preventability of such complications, especially given the current efforts to establish heroin maintenance as an optional treatment for heroin dependence.

Topics: Adult; Cognition Disorders; Drug Prescriptions; Female; Health Status; Heroin; Heroin Dependence; Humans; Male; Myoclonus; Narcotics; Substance-Related Disorders; Surveys and Questionnaires; Time Factors

To investigate the effect of heroin on purine nucleotides catabolism, a rat model of heroin administration and withdrawal was established. Concentrations of uric acid, creatinine, and urea nitrogen in plasma and ADA in plasma, brain, liver, and small intestine were tested. When two heroin administration groups were compared with the control group, the concentrations of plasma uric acid and ADA in plasma, brain, liver, and small intestine increased, whereas the plasma urea nitrogen concentrations in two heroin administration groups and the plasma creatinine concentration in the 3-day heroin administration group did not increase. It seemed that heroin exposure for a short time did not affect renal clearance rate notably. When two withdrawal groups were compared with two heroin administration groups, the concentrations of plasma uric acid and ADA in liver and small intestine decreased, but there was no significant reduction in ADA concentrations of the brain, while the plasma ADA concentrations in the two withdrawal groups were significantly higher than those of two heroin administration groups. When the two withdrawal groups were compared with the control group, there was no significant difference in the concentrations of plasma uric acid and ADA in liver and small intestine, while the concentrations of ADA in plasma and brain were still higher than those of the control group. The results imply that heroin administration may enhance the catabolism of purine nucleotides in the brain and other tissues by increased concentration of ADA and the effect may last for a long time in the brain.

Topics: Adenosine Deaminase; Animals; Brain; Disease Models, Animal; Heroin; Heroin Dependence; Male; Purine Nucleotides; Rats; Rats, Wistar; Substance Withdrawal Syndrome; Urea; Uric Acid

Topics: Heroin; Heroin Dependence; Humans; Spinal Cord Diseases

This article investigates behaviours that may be associated HIV infection among users and sellers of crack, powder cocaine and heroin in central Harlem. Chain referral sampling and other strategies were combined to acquire a sample of 637 (Users = 546; Sellers = 91) who provided urine specimens that were tested for the presence of drugs and HIV. Nearly a quarter (23.9%) of all respondents were HIV positive. Drug injectors were more than 2.5 times more likely to have HIV infections than other respondents (OR = 2.66; 95% CI 1.66-4.26). Those involved in frauds/cons were almost as likely to be HIV positive (OR = 2.58; 95% CI 1.64-4.06). Those with a marital status of being separated, divorced or widowed were twice as likely to be HIV infected (OR 2.16; 95% CI 1.43-3.25). Respondents currently having multiple partner sex (OR = 1.66; 95% CI 1.1-2.51) or who were female (OR = 1.66; 95% CI 1.12-2.45) were more than 1.5 times more likely to be HIV positive. Thus, controlling for lifetime drug injection and current multiple partner sex, other factors, such as participating in frauds/cons, as well as relationship status and being female, were also associated with HIV infection.

Topics: Adult; Chi-Square Distribution; Cocaine; Cocaine-Related Disorders; Crack Cocaine; Female; Heroin; Heroin Dependence; HIV Infections; Humans; Male; Middle Aged; New York City; Regression Analysis; Risk Factors; Risk-Taking; Sex Factors; Urban Health

Using a rat relapse model, we previously reported that re-exposing rats to a drug-associated context, following extinction of operant responding in a different context, reinstates heroin seeking. In an initial pharmacological characterization, we found that the mGluR2/3 agonist LY379268, which acts centrally to reduce evoked glutamate release, attenuates context-induced reinstatement of heroin seeking when injected systemically or into the ventral tegmental area, the cell body region of the mesolimbic dopamine system. Here, we tested whether injections of LY379268 into the nucleus accumbens (NAc), a terminal region of the mesolimbic dopamine system, would also attenuate context-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin; drug infusions were paired with a discrete tone-light cue. Subsequently, lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. After extinction of responding, LY379268 was injected to different groups of rats into the NAc core or shell or into the caudate-putamen, a terminal region of the nigrastriatal dopamine system. Injections of LY379268 into the NAc shell (0.3 or 1.0 microg) dose-dependently attenuated context-induced reinstatement of heroin seeking. Injections of 1.0 microg of LY379268 into the NAc core had no effect, while a higher dose (3.0 microg) decreased this reinstatement. Injections of LY379268 (3.0 microg) 1.5 mm dorsal from the NAc core into the caudate-putamen were ineffective. Results suggest an important role of glutamate transmission in the NAc shell in context-induced reinstatement of heroin seeking.

Topics: Amino Acids; Animals; Behavior, Animal; Bridged Bicyclo Compounds, Heterocyclic; Conditioning, Operant; Dose-Response Relationship, Drug; Enzyme Activation; Extinction, Psychological; Heroin; Heroin Dependence; Male; Narcotics; Nucleus Accumbens; Rats; Rats, Long-Evans; Receptors, Metabotropic Glutamate; Secondary Prevention; Self Administration

Chronic exposure to heroin is known to cause cognitive deficits. However, little is known about the underlying molecular mechanisms. It has been suggested that opiate-induced neurotoxicity as well as impaired plasticity and regeneration may be relevant. One of the target regions where regeneration still can be observed in the adult brain is the hippocampus. Since polysialic acid neural cell adhesion molecule is regarded as one of the key players involved in plasticity and regeneration of neural tissue, we analyzed polysialic acid neural cell adhesion molecule expression in the fascia dentate hilus of the human hippocampus of 29 lethally intoxicated heroin addicts and matched controls. Immunohistochemistry with an antibody directed against polysialic acid neural cell adhesion molecule revealed its expression in differently sized cells which could be identified as neurons and glial cells. We observed an increase in the percentage of polysialic acid neural cell adhesion molecule positive neurons in hippocampal hilus of heroin addicts compared with controls (P = 0.001).Interestingly, we also observed polysialic acid neural cell adhesion molecule expression in glial cells as evidenced by double immunofluorescence with glial fibrillary acidic protein and polysialic acid neural cell adhesion molecule using confocal laser scanning microscopy. The fraction of polysialic acid neural cell adhesion molecule positive glial cells was also higher in heroin addicts compared with controls (P = 0.009). In addition, within the group of addicts morphine blood concentrations showed a positive correlation with the percentage of polysialic acid neural cell adhesion molecule positive neurons (P = 0.04; r = 0.547). In conclusion, we observed an increase in polysialic acid neural cell adhesion molecule positive neurons and glial cells in hippocampi of heroin addicts. This might reflect an attempt to repair cell damage due to heroin exposure.

Topics: Adolescent; Adult; Biomarkers; Cognition Disorders; Dose-Response Relationship, Drug; Female; Glial Fibrillary Acidic Protein; Heroin; Heroin Dependence; Hippocampus; Humans; Male; Narcotics; Nerve Regeneration; Neural Cell Adhesion Molecule L1; Neuroglia; Neuronal Plasticity; Neurons; Sialic Acids; Up-Regulation

Several medications are approved for treatment of opiate abuse, but determinants of their clinical effectiveness are not completely understood. States of opiate dependence or withdrawal may constitute one important set of determinants. To test this hypothesis, the effects of naloxone, buprenorphine, and methadone were assessed on choice between heroin and food in nondependent rhesus monkeys and in heroin-dependent monkeys undergoing withdrawal. A choice procedure was used to permit dissociation of medication effects on the relative reinforcing properties of heroin from nonselective effects on response rates. In nondependent monkeys, increasing unit doses of heroin (0-0.1 mg/kg/injection) maintained dose-dependent increases in heroin choice. Chronic 5-day treatment with naloxone (0.01-0.32 mg/kg/h) or buprenorphine (0.01-0.1 mg/kg/day) produced dose-dependent rightward shifts in heroin choice dose-effect curves, whereas chronic methadone (0.1-0.56 mg/kg/h) had little effect on heroin choice up to doses that suppressed responding. In heroin-dependent monkeys, opiate withdrawal produced overt abstinence signs as well as increases in heroin choice, manifested as leftward shifts in heroin choice dose-effect curves. The withdrawal-associated increases in heroin choice suggest that opiate withdrawal increased the relative reinforcing efficacy of heroin in comparison with food, an effect that may be related to relapse in humans. Methadone prevented withdrawal-associated increases in heroin choice, whereas buprenorphine was less effective. These findings suggest that agonist medications such as methadone may derive their clinical utility from their ability to attenuate withdrawal-associated increases in opiate reinforcement. Moreover, this procedure may be useful for exploring mechanisms underlying withdrawal-associated increases in opiate reinforcement and for testing candidate medications.

Topics: Animals; Buprenorphine; Disease Models, Animal; Feeding Behavior; Heroin; Heroin Dependence; Macaca mulatta; Male; Methadone; Naloxone; Self Administration; Substance Withdrawal Syndrome

We present an unusual case of breast ulceration secondary to heroin injection in a pregnant woman.

Topics: Adult; Breast Diseases; Cellulitis; Female; Heroin; Heroin Dependence; Humans; Narcotics; Necrosis; Pregnancy; Pregnancy Complications; Ulcer

The distribution of naloxone to heroin users is a suggested intervention to reduce overdose and death rates. However, the level of willingness of drug users to administer this medication to others is unclear. Drug users recruited from the community between January 2002 and January 2004 completed a structured interview that assessed topics including drug use, overdose history, and attitudes toward using overdose remedies to assist others. Of the 329 drug users, 82% had used heroin and 64.3% reported that they had injected drugs. Nearly two thirds (64.6%) said that they had witnessed a drug overdose and more than one third (34.6%) had experienced an accidental drug overdose. Most participants (88.5%) said that they would be willing to administer a medication to another drug user in the event of an overdose. Participants who had used heroin (p = .024), had injected drugs (p = .022), had witnessed a drug overdose (p = .001), or had a history of one or more accidental drug overdoses (p = .009) were significantly more willing to treat a companion who had overdosed. Drug users were willing to use naloxone in the event of a friend's overdose. Specific drug use and overdose histories were associated with the greatest willingness to administer naloxone.

Topics: Adolescent; Adult; Cocaine; Cocaine-Related Disorders; Drug Overdose; Female; Friends; Helping Behavior; Heroin; Heroin Dependence; Humans; Interpersonal Relations; Male; Naloxone; Narcotic Antagonists; Psychotic Disorders

Both pre-clinical and clinical studies make feasible the use of vaccines as novel therapeutic medications to treat drug addiction. No reports to date have shown the development of structural models of opiate candidate vaccines for treating human addiction to such compounds. Here we report on the initial development of a novel structural formulation of a bi-valent vaccine against morphine/heroin. This vaccine was able to trigger and establish a high titer antibody response to haptenized drug with antibodies displaying equivalent specificities for both morphine and heroin. Such antibodies did not cross-recognize structurally dissimilar opiate medications. Furthermore, the evaluation of the potential therapeutic effectiveness of this vaccine was targeted to relapse prevention using a schedule of heroin delivery in the rat self-administration model. Antibodies against heroin blocked its reinforcing effects in rodents. The type of carrier protein used in this vaccine allows further evaluation of its potential therapeutic value for preventing relapse to heroin addiction in humans.

Topics: Animals; Antibodies; Antibody Specificity; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Haptens; Heroin; Heroin Dependence; Male; Models, Animal; Models, Chemical; Morphine; Morphine Dependence; Rats; Secondary Prevention; Tetanus Toxoid; Vaccines, Conjugate

Immunohistochemical distribution patterns of neuropeptide FF (NPFF) and neuropeptide tyrosine (NPY) were studied in the brain of rats submitted to two different protocols of heroin treatment. In drug-naive rats, acutely injected heroin significantly depleted NPFF-immunoreactive material within the neurons of the nucleus of solitary tract (NTS), significantly decreased the density of NPFF-immunoreactive nerve fibers within the median eminence, pituitary stalk, and neurohypophysis, and markedly increased NPY-immunoreactive neurons and nerve fibers in the thalamic paraventricular nucleus and bed nucleus of stria terminalis. In drug-sensitized rats, heroin significantly increased the number and immunostaining intensity of the NPFF-immunoreactive neurons within the NTS and induced minor changes in the NPFF-immunoreactive nerve fiber network of the median eminence, pituitary stalk, and neurohypophysis and a relatively minor increase in NPY neurons in the thalamic paraventricular nucleus and bed nucleus of stria terminalis. These heroin-induced changes suggest that NPFF is involved in regulating the effects of the heroin injection and in the mechanisms underlying behavioral sensitization. They also add further support to the key role of NPY in any conditions tending to change the animal homeostasis.

Topics: Animals; Brain; Brain Chemistry; Disease Models, Animal; Heroin; Heroin Dependence; Hypothalamo-Hypophyseal System; Immunohistochemistry; Male; Midline Thalamic Nuclei; Narcotics; Neuropeptide Y; Oligopeptides; Pituitary Gland; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Septal Nuclei; Solitary Nucleus

Prenatal exposure of mice to heroin resulted in behavioral deficits present at adulthood, and related to septohippocampal cholinergic innervation accompanied by both pre- and postsynaptic cholinergic hyperactivity; including an increase in membrane PKC activity, and a desensitization of PKC to cholinergic input, which correlated highly with the behavioral performance, and was reversed by cholinergic grafting. The effect was shown in the behaviorally relevant PKCgamma and beta whereas the less behaviorally relevant PKCalpha isoform was not affected. The present study was designed to establish the effect of heroin exposure on the expression of the PKC isoforms level and on the more functionally relevant cholinergic translocation/activation of the isoforms throughout postnatal development. The hippocampi of mice pups, exposed to heroin transplacentally, were assayed after incubation with carbachol for PKC isoforms on postnatal days (PN) 1, 7, 14, 21, 30 and 50. Prenatal heroin exposure increased basal PKCgamma, beta and alpha levels. PKCgamma and alpha levels returned to control levels on PN50. While in PKCbeta, this increase lasted until PN50. Translocation/activation of the PKC isoforms gamma and beta by cholinergic receptor stimulation was present from PN1, concurrent with the presence of the isoforms. Prenatal exposure to heroin completely abolished the translocation/activation throughout the entire postnatal development. This defect was shown from the very beginning, PN1, the day when the PKC isoforms appear. The results suggest that the PKCgamma and beta isoforms are functional concurrent with their developmental appearance. Unlike findings on some other teratogens, the prenatal heroin effect on the isoforms function is similar throughout postnatal development.

Topics: Acetylcholine; Analgesics, Opioid; Animals; Animals, Newborn; Cholinergic Agonists; Cholinergic Fibers; Disease Models, Animal; Enzyme Activation; Female; Heroin; Heroin Dependence; Hippocampus; Male; Mice; Neural Pathways; Organ Culture Techniques; Pregnancy; Prenatal Exposure Delayed Effects; Protein Isoforms; Protein Kinase C; Protein Transport; Receptors, Cholinergic; Septal Nuclei

To describe the circumstances surrounding recent heroin overdose among a sample of heroin overdose survivors and the links to their knowledge of overdose risk.. A cross-sectional survey of 257 recent non-fatal heroin overdose survivors was undertaken to examine self-reported knowledge of overdose risk reduction strategies, behaviour in the 12 h prior to overdose and attributions of overdose causation.. Most of the overdoses occurred in public spaces as a result of heroin use within 5 min of purchasing the drug. A substantial number of overdoses occurred with no one else present and/or involved the concomitant use of other drugs. While knowledge of at least one overdose prevention strategy was reported by 90% of the sample, less then half of the sample knew any single strategy. Furthermore knowledge of the dangers of mixing benzodiazepines and/or alcohol with heroin was associated with an increased likelihood of such mixing being reported prior to overdose.. While heroin users can articulate knowledge of key overdose risk reduction strategies, this knowledge was not generally associated with a reduction in risk behaviours but was in some cases associated with increased reports of overdose risk behaviours. Further research is required in order to better understand this paradoxical effect, focussing on risk reduction education amenable to the social contexts in which heroin use takes place.

Topics: Adolescent; Adult; Attitude to Health; Australia; Catchment Area, Health; Cognition; Cross-Sectional Studies; Drug Overdose; Female; Harm Reduction; Heroin; Heroin Dependence; Humans; Male; Naloxone; Narcotic Antagonists; Resuscitation; Risk-Taking; Surveys and Questionnaires

The United Kingdom is unusual internationally in that it is one of few countries able to prescribe diamorphine for the treatment of opiate dependence. Prescribing diamorphine has been part of the UK response to drug problems since the 1920s. Despite this, little is known about who receives diamorphine and how treatment is delivered. This study aims to describe the characteristics and treatment regimes of opiate-dependent drug users receiving a prescription for diamorphine in the United Kingdom in 2000, and report on their status in 2002. A retrospective case-note review was conducted in England and Wales. Two hundred and ten (72%; 210/292) patients' sets of case-notes were reviewed at 27 of the 42 (64%) drug clinics where diamorphine was prescribed by the doctor. Patients had been receiving a prescription for diamorphine for a median length of six years. The majority were unemployed white males, with a median age of 44 years. Illicit drug use and criminal activity, while low, had not been eliminated totally. The majority were prescribed ampoules and few had significant health problems. In some cases patients had been transferred to injectable diamorphine from injectable methadone to reduce injection related problems. There were wide variations in dose. The majority of patients had no serious drug, health or social problems. Diamorphine prescribing was a long-term commitment. The experience from the United Kingdom has been one of long-term prescribing with the aim of retaining patients in treatment and reducing the harms caused by illicit drug use. Prospective studies are needed to determine the long-term consequences of receiving a diamorphine prescription.

Topics: Ambulatory Care Facilities; Crime; England; Health Status; Heroin; Heroin Dependence; Humans; Mental Disorders; Narcotics; Practice Patterns, Physicians'; Retrospective Studies; Wales

Topics: Australia; Canada; Drug Overdose; Heroin; Heroin Dependence; Humans; Narcotics

Topics: Australia; Canada; Heroin; Heroin Dependence; Humans; Law Enforcement; Narcotics

Previous studies have largely attributed the Australian heroin shortage to increases in local law enforcement efforts. Because western Canada receives heroin from similar source nations, but has not measurably increased enforcement practices or funding levels, we sought to examine trends in Canadian heroin-related indices before and after the Australian heroin shortage, which began in approximately January 2001.. During periods before and after January 2001, we examined the number of fatal overdoses and ambulance responses to heroin-related overdoses that required the use of naloxone in British Columbia, Canada. As an overall marker of Canadian supply reduction, we also examined the quantity of heroin seized during this period. Lastly, we examined trends in daily heroin use among injection drug users enrolled in the Vancouver Injection Drug Users Study (VIDUS).. There was a 35% reduction in overdose deaths, from an annual average of 297 deaths during the years 1998-2000 in comparison to an average of 192 deaths during 2001-03. Similarly, use of naloxone declined 45% in the period coinciding with the Australian heroin shortage. Interestingly, the weight of Canadian heroin seized declined 64% coinciding with the Australian heroin shortage, from an average of 184 kg during 1998-2000 to 67 kg on average during 2001-03. Among 1587 VIDUS participants, the period coinciding with the Australian heroin shortage was associated independently with reduced daily injection of heroin [adjusted odds ratio: 0.55 (95% CI: 0.50-0.61); P < 0.001].. Massive decreases in three independent markers of heroin use have been observed in western Canada coinciding with the Australian heroin shortage, despite no increases in funding to Canadian enforcement efforts. Markedly reduced Canadian seizure activity also coincided with the Australian heroin shortage. These findings suggest that external global heroin supply forces deserve greater investigation and credence as a potential explanation for the Australian heroin shortage.

Topics: Australia; British Columbia; Drug Overdose; Heroin; Heroin Dependence; Humans; Illicit Drugs; Law Enforcement; Naloxone; Narcotic Antagonists; Narcotics; Substance Abuse, Intravenous

5 heroin addicts (aged 31-44 years; 1 female, 4 men) presented with a history of blurred vision and diplopia followed by dysarthria. 3 of the patients also developed respiratory failure requiring long-term ventilatory support. Physical examination revealed cranial nerve deficits and abscesses at injection sites in 3 of them.. In 4 patients wound botulism was diagnosed on the basis of symptoms, course of the illness and response to specific treatment. Clostridium botulinum was grown from wound swab in one patient.. Two of the patients, having been injected with antitoxin immediately after admission, were discharged almost symptom-free after only a few days. Adjuvant antibiotics and, in 3 patients, surgical débridement of the abscesses were needed.. Progressive cranial nerve pareses in addicts who inject drugs intravenously or intramuscularly should raise the suspicion of wound botulism and require hospitalization. While indirect demonstration of toxin supports the diagnosis, false-negative results are common.

Topics: Adult; Anti-Bacterial Agents; Botulinum Antitoxin; Botulism; Clostridium botulinum; Debridement; Diagnosis, Differential; Female; Follow-Up Studies; Germany; Heroin; Heroin Dependence; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Time Factors; Treatment Outcome; Wound Infection

It is often claimed that the autonomy of heroin addicts is compromised when they are choosing between taking their drug of addiction and abstaining. This is the basis of claims that they are incompetent to give consent to be prescribed heroin. We reject these claims on a number of empirical and theoretical grounds. First we argue that addicts are likely to be sober, and thus capable of rational thought, when approaching researchers to participate in research. We reject behavioural evidence purported to establish that addicts lack autonomy. We present an argument that extrinsic forces must be irresistible in order to make a choice non-autonomous. We argue that heroin does not present such an irresistible force. We make a case that drug-oriented desires are strong regular appetitive desires, which do not compromise consent. Finally we argue that an addict's apparent desire to engage in a harmful act cannot be construed as evidence of irrational or compulsive thought. On these arguments, a sober heroin addict must be considered competent, autonomous and capable of giving consent. More generally, any argument against legalisation of drugs or supporting infringement of the liberty of those desiring to take drugs of addiction must be based on considerations of harm and paternalism, and not on false claims that addicts lack freedom of the will.

Topics: Clinical Trials as Topic; Coercion; Compulsive Behavior; Ethical Analysis; Heroin; Heroin Dependence; Humans; Informed Consent; Mental Competency; Motivation; Paternalism; Research Subjects

Topics: Behavior Control; Clinical Trials as Topic; Compulsive Behavior; Control Groups; Empirical Research; Heroin; Heroin Dependence; Humans; Informed Consent; Mental Competency; Personal Autonomy

Heroin use causes considerable harm to individual users including dependence, fatal and nonfatal overdose, mental health problems, and blood borne virus transmission. It also adversely affects the community through drug dealing, property crime and reduced public amenity. During the mid to late 1990s in Australia the prevalence of heroin use increased as reflected in steeply rising overdose deaths. In January 2001, there were reports of an unpredicted and unprecedented reduction in heroin supply with an abrupt onset in all Australian jurisdictions. The shortage was most marked in New South Wales, the State with the largest heroin market, which saw increases in price, dramatic decreases in purity at the street level, and reductions in the ease with which injecting drug users reported being able to obtain the drug. The abrupt onset of the shortage and a subsequent dramatic reduction in overdose deaths prompted national debate about the causes of the shortage and later international debate about the policy significance of what has come to be called the "Australian heroin shortage". In this paper we summarise insights from four years' research into the causes, consequences and policy implications of the "heroin shortage".

Topics: Adolescent; Adult; Australia; Commerce; Drug and Narcotic Control; Drug Overdose; Emergency Medical Services; Heroin; Heroin Dependence; Humans; Illicit Drugs; Law Enforcement; Middle Aged; Narcotics; Prevalence; Young Adult

Aspects of drug withdrawal may become conditioned to previously neutral environmental stimuli via classical conditioning processes. Nevertheless, the significance of conditioned withdrawal effects in motivating drug intake remains largely unexplored. Here, we investigated the effects of conditioned withdrawal in modulating heroin consumption and brain reward sensitivity in rats. Rats intravenously self-administered heroin (20 microg/infusion) during 0 h (control), 1 h (nondependent), or 23 h (dependent) sessions and had daily intracranial self-stimulation (ICSS) thresholds assessed. ICSS thresholds remained stable and unaltered in control rats. In nondependent rats, heroin self-administration induced a transient activation of reward systems, reflected in lowering of ICSS thresholds. In dependent rats, heroin intake escalated across sessions and was associated with a gradual decrease in reward sensitivity, reflected in progressively elevated ICSS thresholds. Thus, as dependence develops, heroin may be consumed not only for its acute reward-facilitating effects, but also to counter persistent deficits in reward sensitivity. In nondependent rats, the opioid receptor antagonist naloxone (30 microg/kg) increased heroin consumption and reversed heroin-induced lowering of ICSS thresholds, effects resistant to classical conditioning. In contrast, in dependent rats naloxone (30 microg/kg) increased heroin consumption and also elevated ICSS thresholds above their already elevated baseline levels (i.e., precipitated withdrawal). Most importantly, stimuli repeatedly paired with naloxone-precipitated withdrawal provoked heroin consumption and elevated ICSS thresholds in dependent rats. Thus, conditioned stimuli predicting the onset of heroin withdrawal, and hence the reward deficits coupled with this state, may play a critical role in provoking craving and relapse in human opiate addicts.

Topics: Animals; Conditioning, Classical; Disease Models, Animal; Electric Stimulation; Heroin; Heroin Dependence; Male; Naloxone; Narcotic Antagonists; Rats; Reward; Self Stimulation; Substance Withdrawal Syndrome

The purpose of this study was the evaluation of clinical heroin symptoms and buprenorphine drug addiction in the withdrawal period with the purpose of their comparison, study of parameters of bone metabolism in the both groups. In the study group were included 40 patients with heroin and 27 with buprenorphine addiction in the period of abstinence. Our investigations have shown, that in the both groups, among clinical symptoms ossalgias, arthralgias and mialgias attributes to the expressed dysfunction of vegetative system, were most prominent. Decrease of sexual functions was found in half of inspected patients. Biochemical investigations have shown intensive clearance of calcium with the urine that indicates intensifying resorbtion processes in the bone tissue. Symptoms of hypogonadism were accompanied by the decrease of the level of testosterone in the blood. Parameters of mineral consistency of the bone tissue was decreased both in patients with heroin and buprenorphine addiction.

Topics: Behavioral Symptoms; Biomarkers; Bone and Bones; Bone Density; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Dependence; Pain; Radiography; Substance Withdrawal Syndrome

Topics: Administration, Inhalation; Asthma; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome

In this study the use of the various opiate alkaloid contaminants as potential markers for illicit heroin ingestion were investigated. Urine samples (n = 227) taken from prisoners for routine drug screen, which were positive for opiates by immunoassay screening, were analyzed for contaminants in illicit heroin. A previously described method was used for the analysis; urines were extracted using mixed-mode solid-phase extraction; the extracts were derivatized using N-methyl-bistrifluoroacetamide and N-methyl-N-trimethylsilyltrifluoroactamide/trimethylchlorosilane. The derivatized extracts were subjected to electron impact gas chromatography-mass spectrometry. The extracts were injected in full scan mode followed by selected ion monitoring mode for target opiate alkaloids found as contaminants in illicit heroin. The opiate alkaloids and their metabolites specifically targeted included meconine, desmethylmeconine, hydrocotarnine, acetylcodeine, codeine, morphine, 6-monacetylmorphine (6-mam), papaverine, hydroxypapaverine, and dihydroxypapaverine. Of the 227 samples positive for opiates by immunoassay, using a cut-off of 300 ng/mL, 199 were confirmed positive for morphine and using a cut-off of 10 ng/mL, 28 were confirmed positive for 6-mam. Using the screening method described in the study, the following numbers of positives were found: 199 for morphine, 103 for codeine, 5 for meconine, 46 for desmethylmeconine, 18 for 6-mam, 136 for hydroxypapaverine, and 139 for dihydroxypapaverine. Acetylcodeine, hydrocotarnine, and papaverine were not detected in any of the samples. The results of this study show that analysis for papaverine metabolites is more sensitive than 6-mam as a way of demonstrating illicit heroin use.

Topics: Administration, Oral; Heroin; Heroin Dependence; Humans; Morphine Derivatives; Narcotics; Opium; Prisoners; Substance Abuse Detection

Topics: Analgesics, Opioid; Canada; Heroin; Heroin Dependence; Humans; Methadone; Randomized Controlled Trials as Topic

Australian heroin markets have recently undergone dramatic change, sparking debate about the nature of such markets. This study aimed to determine the onset, peak and decline of the heroin shortage in New South Wales (NSW), using the most appropriate available methods to detect market level changes. The parameters of the heroin shortage were determined by reviewing: reports of heroin users about availability and price (derived from the existing literature and the Illicit Drug Reporting System); qualitative interviews with injecting drug users, and health and law enforcement professionals working in the illicit drug field; and examining data on heroin seizures over the past decade. There was a marked reduction in heroin supply in NSW in early 2001. An increase in the price of heroin occurred in 2001, whereas it had decreased steadily since 1996. A reduction in purity also occurred, as reported by drug users and heroin seizures. The peak period of the shortage appears to have been January to April 2001. The market appears to have stabilised since that time, although it has not returned to pre-2001 levels: heroin prices have decreased in NSW for street grams, but not to former levels, and the price of 'caps' (street deals) remain elevated. Heroin purity in NSW has remained low, with perhaps a 10% increase above the lowest recorded levels. These data support the notion that the heroin market in NSW underwent significant changes, which appear to have involved a lasting shift in the nature of the market.

Topics: Commerce; Documentation; Heroin; Heroin Dependence; Humans; Illicit Drugs; New South Wales

Increasing heroin use in Australia over the past 30 years has been associated with a decline in the age of initiation to heroin use. The 2001 Australian heroin shortage was used to assess the effects of a reduction in heroin supply on age of initiation into heroin injecting. Data collected from regular injecting drug users (IDU) over the period 1996 - 2004 as part of the Australian Illicit Drug Reporting System were examined for changes in self-reported age of first heroin use after the onset of the heroin shortage. Estimates were also made of the number of young people who may not have commenced injecting heroin during the heroin shortage. The proportion of IDU interviewed in the IDRS who were aged

Topics: Adolescent; Adult; Age Factors; Age of Onset; Australia; Commerce; Heroin; Heroin Dependence; Humans; Prevalence; Substance Abuse, Intravenous

In early 2001 Australia experienced a sudden reduction in the availability of heroin which had widespread effects on illicit drug markets across the country. The consequences of this event, commonly referred to as the Australian 'heroin shortage', have been extensively studied and there has been considerable debate as to the causes of the shortage and its implications for drug policy. This paper aims to investigate the presence of these epidemic patterns, to quantify the scale over which they occur and to estimate the relative importance of the 'heroin shortage' and any epidemic patterns in the drug markets.. Key indicator data series from the New South Wales illicit drug market were analysed using the statistical methods Principal Component Analysis and SiZer.. The 'heroin shortage' represents the single most important source of variation in this illicit drug market. Furthermore the size of the effect of the heroin shortage is more than three times that evidenced by long-term 'epidemic' patterns.. The 'heroin shortage' was unlikely to have been a simple correction at the end of a long period of reduced heroin availability, and represents a separate non-random shock which strongly affected the markets.

Topics: Amphetamine; Amphetamine-Related Disorders; Cluster Analysis; Cocaine; Cocaine-Related Disorders; Drug and Narcotic Control; Heroin; Heroin Dependence; Humans; Illicit Drugs; Law Enforcement; New South Wales; Normal Distribution; Principal Component Analysis; Time Factors

Topics: Adult; Brain Diseases; Heroin; Heroin Dependence; Humans; Inhalation; Magnetic Resonance Imaging; Male

Heroin has been shown to elevate dopamine (DA) level. It is well known that an increase in DA oxidative metabolism leads to increased reactive oxygen species (ROS) formation, and thus, ROS have been frequently associated with neuronal cell death due to damage to carbohydrates, amino acids, phospholipids, and nucleic acids. This study investigated whether there are oxidative stress and effects of exogenous antioxidants in heroin-administered mice. The heroin-dependent mice model was made via intraperitoneal injection. Oxidative damage of DNA, protein, and lipid was measured by analysis of single cell electrophoresis, the 2,4-dinitrophenylhydrazine method, and thiobarbituric acid method respectively. The activities of antioxidative enzymes and total antioxidant capacity were assayed by spectrophotometry. After administration with heroin, the mice not only showed decrease of total antioxidant capacity in serum and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione (GSH) peroxidase in brain, but also exhibited the oxidative damages of DNA, protein and lipid. On the other hand, exogenous antioxidants could restrain the oxidative stress, even alleviate withdrawal syndrome in heroin-administered mice. Our results also imply a possibility that ROS may participate in the whole process of dependence and withdrawal of heroin. Therefore, strategies of blocking oxidative stress may be useful in the development of therapy for opiate abuse.

Topics: Animals; Antioxidants; Brain; Brain Chemistry; Catalase; DNA Damage; Female; Glutathione Peroxidase; Heroin; Heroin Dependence; Injections, Intraperitoneal; Injections, Subcutaneous; Lymphocytes; Male; Malondialdehyde; Mice; Naloxone; Narcotic Antagonists; Narcotics; Oxidative Stress; Substance Withdrawal Syndrome; Superoxide Dismutase

The purpose of this paper is to identify characteristics of heroin sniffers likely to shift to injection by evaluating the street addict role theory as an informing theoretical framework to explain transition from heroin sniffing to injection. A nested case-control research design was used to identify 142 heroin sniffers who never had injected a drug (controls) and 146 recently transitioned injection drug users (cases) from a larger study of 600 African-American, Hispanic, and non-Hispanic white men and women who were street recruited from multiple communities known for high drug use. Univariate and multivariate logistic regression analyses were conducted to test the proposed hypotheses derived from the street addict role theory. Our findings partially support the utility of the street addict role perspective as an explanatory framework for understanding the role played by sociocultural factors in the transition to injection. This perspective can help contextualize this HIV-related behavior within the high risk social environment of heroin users. The development of effective prevention strategies for this group should be guided by a comprehensive understanding of the social environment where HIV-related risk behaviors occur.

Topics: Administration, Inhalation; Adolescent; Adult; Black or African American; Case-Control Studies; Cultural Characteristics; Female; Heroin; Heroin Dependence; Hispanic or Latino; Humans; Injections, Intravenous; Male; Risk Factors; Sexual Behavior; Social Environment; Socioeconomic Factors

Topics: Animals; Conditioning, Classical; Disease Models, Animal; Electric Stimulation; Heroin; Heroin Dependence; Male; Naloxone; Narcotic Antagonists; Rats; Reward; Self Stimulation; Substance Withdrawal Syndrome

Topics: Adult; Heroin; Heroin Dependence; Humans; Injections; Male; Necrosis; Scalp Dermatoses; Skin; Skin Ulcer

The survival of heroin overdose patients resuscitated from cardiac arrest is reported to be poor. The aim of our study was to investigate the outcome and characteristics of survivors after cardiac arrest caused by heroin overdose.. This was a retrospective study in a medium-sized city (population, 560,000). Between 1 January 1997 and 31 December 2000, there were 94 combined cardiac arrests caused by acute drug poisonings. The main outcome measure was survival to discharge.. Cardiopulmonary resuscitation was attempted in 19 heroin overdose patients (group A) and in 53 patients with cardiac arrest caused by other poisonings (group B). Three (16%) vs. six (11%) patients were discharged alive (group A vs. B, respectively). The survivors in group A had an Emergency Medical Service (EMS)-witnessed cardiac arrest or the Emergency Dispatching Centre was called before the arrest occurred. There was no statistically significant difference between the two groups in terms of survival. Survivors in both groups suffered from acute renal failure (two), hypoglycaemia (four) and hypothermia (three).. Survival after cardiac arrest caused by heroin overdose is possible if the arrest is EMS witnessed or the Emergency Dispatching Centre is called before the cardiac arrest occurs. In comparison with cardiac arrests caused by other poisonings, there was no difference in survival. The incidence and mechanism of hypoglycaemia should be examined in further studies.

Topics: Adult; Cardiac Output; Cardiopulmonary Resuscitation; Drug Overdose; Emergency Medical Services; Epinephrine; Female; Finland; Heart Arrest; Heroin; Heroin Dependence; Humans; Hypoglycemia; Male; Middle Aged; Narcotics; Rhabdomyolysis; Survival; Vasoconstrictor Agents

The UK heroin market is the biggest in Europe and approximately 70% of heroin deaths are due to fatal poisoning. Methadone treatment for heroin addiction in the UK, the 'British system', is unique as it is largely provided by General Practitioners.. The Office for National Statistics provided data on deaths, the Home Office provided law enforcement data on drug seizures and the Department of Health data on prescriptions. For methadone treatment we calculated the death rate per 1000 patient years. We used Spearman's rank correlation to assess the association between illicit drug seizures for heroin and methadone and deaths.. Between 1993 and 2004 there were 7072 deaths involving heroin/morphine (86% males) and 3298 deaths involving methadone (83% male). From 1993-1997, directly age-standardized mortality rates for males were similar for both drugs, increasing from approximately 5 to 15 per million. Mortality rates for heroin continued to increase until 2000, subsequently decreasing from 30 to 20 per million by 2003, and rising again to 24 per million in 2004. In contrast, mortality rates for methadone decreased between 1997 and 2004 to just above 1993 levels. Among females the mortality rate for both drugs was lower than for males throughout the study period, remaining relatively stable. Methadone deaths per 1000 patient years remained similar between 1993 and 1997, after which they fell by three quarters. For both heroin/morphine and methadone, deaths were strongly associated with seizures (Spearmans' coefficient for males: heroin, P = 0.95, P < 0.001 and methadone, P = 0.83, P = 0.0013).. Our study suggests the 'British System' can deliver substantial expansion of treatment without increased mortality risk. The fall in heroin/morphine deaths since 2000 may also be an indication of success of increasing methadone treatment. Data on mortality risk is needed to determine whether increased methadone treatment has reduced drug-related deaths.

Topics: Administration, Oral; Adult; Age Distribution; Drug and Narcotic Control; England; Family Practice; Female; Heroin; Heroin Dependence; Humans; Injections; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Sex Distribution; Tablets; Wales

Topics: Animals; Dogs; Drug Evaluation, Preclinical; Heroin; Heroin Dependence; Humans; Male; Methadone; Treatment Refusal

The concomitant use of cocaine by heroin-dependent subjects, or by patients on methadone maintenance treatment, is a relevant phenomenon that determines the negative consequences on health, social adjustment, and outcome of opioid addiction treatment. Little is known about the patterns of co-use of these two substances and the pathophysiological alterations following this condition. Only a few studies have evaluated the neurochemical effects in subjects carrying this specific pattern of abuse. Similarly, the impact of cocaine abuse on psychiatric and social function in subjects already affected by opioid addiction is still poorly understood and further studies are necessary to investigate this specific area that could profoundly affect methadone maintenance treatment. The aim of this article is to investigate the psychopathological symptoms of heroin-cocaine abuse in a group of heroin addicts applying for treatment. Results show a direct relationship between cocaine abuse and a higher rate of psychiatric disorders, but a negative correlation with the severity of self-rated psychopathology.

Topics: Adult; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Drug Interactions; Female; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Narcotics

To assess whether chronic heroin abuse may generate vascular central nervous deficits, we studied the profile of vascular alterations in 17 heroin addicts (14 males mean age 31 years, range 23-39 years and 3 females mean age 33 years, range 30-35 years) before and, in one of them, 10 weeks after an ultra-rapid heroin detoxification. Using the functional technique of single-photon emission tomography (SPET) with 740 MBq of (99m)Tc-hexametazine (HMPAO) and computational brain-mapping techniques by means of a Talairach analysis, we determined the pattern of vascular brain alterations associated with chronic heroin abuse. Compared with controls, subjects who had used heroin chronically showed a decrease of global brain perfusion that was more significant in the frontal cortex-mainly in orbito-frontal regions, as well as in the occipital and temporal lobes. All patients showed marked asymmetric perfusion of the basal ganglia and the majority of them showed also an asymmetric perfusion of cerebellum. In addition, there were small activated areas dispersed in the occipital lobe (3 of 17) and apex region (4 of 17). In conclusion, decreased perfusion in heroin addicts was found in regions involved in the control of attention, motor speed, memory and visual-spatial processing. The prefrontal cortex is involved in decision making and inhibitory control, processes disturbed in heroin addicts who have stopped heroin consumption. A reduction in regional perfusion may reflect ongoing subtle neurocognitive deficits, which are consistent with the maintenance of asymmetry of the basal nuclei.

Topics: Adult; Brain; Cohort Studies; Female; Heroin; Heroin Dependence; Humans; Male; Tomography, Emission-Computed, Single-Photon

Recent data from our laboratory have demonstrated that appetitive drug memories undergo protein synthesis-dependent reconsolidation in the basolateral amygdala (BLA), an area important in the formation of emotional memories. We here investigated the importance of the BLA in the reconsolidation of opiate conditioned withdrawal memories. Rats with bilateral cannulas implanted in the BLA were trained to respond for heroin (0.12 mg/kg, i.v.) under a seeking-taking schedule, which required responding on a seeking lever to gain the opportunity to self-administer heroin by a single response on a taking lever. After induction of opiate dependence with subcutaneously implanted, heroin-filled osmotic minipumps (3 mg x kg(-1) x d(-1) heroin), rats received five consecutive pairings of a conditioned stimulus (CS) (tone, light, and odor compound) paired with naloxone (0.10 mg/kg, s.c.)-precipitated withdrawal. We replicated our previous findings that heroin seeking is suppressed in the presence of the withdrawal-associated CS. However, infusion of Zif268 antisense oligodeoxynucleotide into the BLA before reactivation of the CS-withdrawal association abolished this conditioned suppression in a reactivation-dependent manner. We also report that reconsolidation of CS-withdrawal memories upregulates Zif268 protein in the basolateral but not central nucleus of the amygdala and that Zif268 knockdown occurs selectively in the BLA. These results demonstrate that drug withdrawal memories undergo protein synthesis-dependent reconsolidation in the BLA and suggest a common mechanism for the reconsolidation of both appetitive and aversive drug memories.

Topics: Amygdala; Animals; Behavior, Addictive; Conditioning, Psychological; Early Growth Response Protein 1; Heroin; Heroin Dependence; Male; Memory; Rats; Substance Withdrawal Syndrome

A 37-year-old man with a 19-years history of injection drug use (IDU) who had acquired a chronic hepatitis C virus (HCV-) infection 9 years ago, entered the German clinical study on heroine assisted treatment ("Modellprojekt zur heroingestützten Behandlung Opiatabhängiger"). Before study onset he received buprenorphine maintainance treatment, while at the same time engaging in illicit IDU (heroine, cocaine). He lived in a caravan and was on social welfare.. PCR revealed a genotype 2 and an HCV-viral load of 310,000 IU/ml. Liver biopsy showed a moderate chronic active hepatitis and a mild portal fibrosis without signs of liver cirrhosis.. Within the heroine-assisted treatment program the patient injected heroine under medical supervision several times a day and attended the standardized psychosocial program that comprised an intensive education on HCV-infection. Within a period of ten months of physical and social stabilization he managed to stop illicit drug use, found stable housing and started to work. We then initiated treatment of HCV-infection. Subcutaneous pegylated interferon alpha-2a, peroral ribavirin and intravenous heroine were administered as directly observed therapy. Based on the close mashed care of the heroine assisted treatment setting, side effects were well controllable and reversible after the end of antiviral therapy. A sustained response was obtained.. After careful indication, heroine-assisted treatment with particularly intensive medical and psychological care can offer appropriate conditions for a save and successful treatment of hepatitis C as well as for a sustained result.

Topics: Administration, Oral; Adult; Antiviral Agents; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Comorbidity; Drug Therapy, Combination; Hepatitis C, Chronic; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Male; Polyethylene Glycols; Recombinant Proteins; Rehabilitation, Vocational; Ribavirin; Social Adjustment; Social Welfare; Substance Abuse, Intravenous

Topics: Delivery of Health Care; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Opioid-Related Disorders; United Kingdom

Study 1: The aim of this study was to analyze in persons detoxified of heroin, compensatory conditioned responses (CCRs) that are opposite to the unconditioned physiological, and subjective effects that are induced by this substance. The procedure consisted in presenting slides with images of neutral stimuli (NSs) and conditioned stimuli (CSs) of heroin to both non-addicted and detoxified addicted persons. The evaluated responses were heart rate (HR) and desire for heroin (DH). Study 2: The aim was to facilitate the emission of mimetic conditioned responses (MCRs) to the unconditioned physiological, and subjective effects of heroin in detoxified heroin addicts. Three different stimulus series were manipulated: SA, during which the participant remained alone; SB, administration of a needle prick given by the researcher; SC, performance of the "pump" ritual without drug by the participants. The responses measured were HR and DH. The results of both studies are considered, respectively, to be indicators of compensatory and mimetic conditioned responses.

Topics: Adult; Conditioning, Classical; Cues; Female; Habits; Heart Rate; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Needles; Photic Stimulation; Physical Stimulation; Punctures; Stress, Psychological; Substance-Related Disorders; Syringes

In 2001 the supply of heroin was substantially reduced across Australia. Given the child protection concerns associated with the use of substances by pregnant women, it was pertinent to examine how the reduction in the supply of heroin affected this community of users. This paper aimed to assess the extent of any drug-related problems among pregnant women associated with the reduction in heroin supply in New South Wales (NSW).. Two sources of data were used: (1) Data on hospital visits in NSW in which drug and alcohol problems were noted as complicating the pregnancy; and (2) Key informant reports from services targeting substance-using pregnant women across the three main Sydney drug markets.. The shortage did not affect the number of hospital separations for substance-using pregnant women, nor the number of women referred to services for substance use in pregnancy. Key informants reported an increase in the use of cocaine among pregnant women and a change in injection sites for some women (including into breast tissue). No substantial change in adverse outcomes was observed to be associated with this change in patterns of drug use.. The reduction in heroin supply appeared to have limited impact on the number of substance-using pregnant women as assessed by hospital episodes and key informant reports. The evidence suggested an increase in the injecting of cocaine by pregnant women using drug treatment services, similar to the changes in drug use patterns observed among other groups of injecting drug users. The lack of change observed in the qualitative and statistical data regarding adverse health consequences associated with cocaine injecting suggests the potentially negative impact of maternal cocaine use on infant health may be difficult to detect and monitor.

Topics: Adult; Attitude to Health; Drug Overdose; Female; Health Education; Heroin; Heroin Dependence; Humans; Illicit Drugs; Maternal Behavior; Narcotics; New South Wales; Pregnancy; Pregnancy Complications; Substance Abuse, Intravenous; Surveys and Questionnaires

The alteration of peripheral blood T-and B-lymphocyte proliferative responses were determined during different periods of withdrawal in heroin (Hw) and heroin / bhang (HBw) addicts. The results clearly demonstrated a significant decrease in the response of T- lymphocytes to PHA-stimulation and secretion of IL-2 in both Hw and HBw addicts. The in vitro presence of naloxone induced further inhibition of the PHA proliferative response and IL-2 production. Our data also indicated a significant suppression of IFN-gamma levels by human blood lymphocytes from Hw and HBw addicts. Additionally, a significant suppression of IFN-gamma production was demonstrated in the presence of naloxone. Moreover, IL-4 production was suppressed in Hw, but not in HBw groups and the in vitro presence of naloxone did not affect the level of IL-4 in both groups. However, IL-10 production was significantly increased in both groups accompanied by a significant suppression of IL-10 secretion in the presence of naloxone. In contrast, IL-5 levels stimulated by PHA showed a significant increase in both groups, while no significant effect of naloxone could be observed. Our results suggested that heroin administration can cause measurable suppression of some components of the human cellular immune system. The results further demonstrated that the immunsuppressive effect observed after heroin use are naloxone-mediated and suggested that activation of the adrenal gland is one potential mechanism for this effect.

Topics: Adrenocorticotropic Hormone; Adult; B-Lymphocytes; Heroin; Heroin Dependence; Humans; Hydrocortisone; Interferon-gamma; Interleukins; Lymphocyte Activation; Male; Naloxone; Narcotic Antagonists; Phytohemagglutinins; Substance Withdrawal Syndrome; T-Lymphocytes

To examine the impact of a sudden and dramatic decrease in heroin availability, concomitant with increases in price and decreases in purity, on fatal and non-fatal drug overdoses in New South Wales, Australia.. Time-series analysis was conducted where possible on data on overdoses collected from NSW hospital emergency departments, the NSW Ambulance Service, and all suspected drug-related deaths referred to the NSW Coroner's court.. The number of suspected drug-related deaths where heroin and other drugs were mentioned; ambulance calls to suspected opioid overdoses; and emergency department admissions for overdoses on heroin and other drugs.. Both fatal and non-fatal heroin overdoses decreased significantly after heroin supply reduced; the reductions were greater among younger age groups than older age groups. There were no clear increases in non-fatal overdoses with cocaine, methamphetamines or benzodiazepines recorded at hospital emergency departments after the reduction in heroin supply. Data on drug-related deaths suggested that heroin use was the predominant driver of drug-related deaths in NSW, and that when heroin supply was reduced overdose deaths were more likely to involve a wider combination of drugs.. A reduction in heroin supply reduced heroin-related deaths, and did not result in a concomitant increase, to the same degree, in deaths relating to other drugs. Younger people were more affected by the reduction in supply.

Topics: Adolescent; Adult; Age Distribution; Alcohol Drinking; Antidepressive Agents; Cocaine; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Methamphetamine; Mortality; New South Wales; Sex Distribution

Topics: Drug Overdose; Heroin; Heroin Dependence; Humans

To investigate the role of recent life problems in non-fatal overdose among heroin users entering various drug treatment settings.. Cross-sectional data from a longitudinal study investigating drug treatment effectiveness.. Five prison drug treatment services, three residential rehabilitation units, three residential detoxification units and 21 community drug treatment services located in rural, urban and inner-city areas of Scotland.. Of a total of 793 primary heroin users commencing drug treatment during 2001-02, 337 (42.5%) were prison drug service clients; 91 (11.5%) were residential rehabilitation clients; 97 (12.2%) were residential detoxification clients; and 268 (33.8%) were community drug treatment clients.. Univariate and stepwise multivariate logistic regression analyses examined associations between overdosing in the 90 days prior to treatment entry and basic demographic characteristics, recent drug use and recent life problems.. Ninety-one study participants (11.5%) reported at least one overdose and 19 (2.4%) reported more than one overdose in the 90 days prior to treatment entry. A chi2 test revealed no significant difference in rates of recent overdosing between the four treatment settings (P = 0.650). Recent drug use and recent life problems-but not demographic characteristics-were associated independently with recent overdosing. However, recent life problems were not associated independently with recent overdosing among clients entering prison, clients entering residential rehabilitation or with multiple recent overdosing.. Associations between recent life problems and recent overdose were evident, but varied by treatment setting. Treatment providers should identify and address heroin users' life problems as part of a broad strategy of overdose prevention.

Topics: Adolescent; Adult; Drug Overdose; Epidemiologic Methods; Female; Heroin; Heroin Dependence; Humans; Life Change Events; Male; Middle Aged; Scotland; Suicide, Attempted

At the end of 2000, in Sydney, Australia, there was a dramatic reduction in heroin availability. This study examines how health agencies treating clients for drug and alcohol related issues were able to respond to the changes that took place in their clients and their treatment needs. Key informant interviews were conducted with 48 staff from a wide range of health services in Sydney to provide the data for a thematic analysis. Changes experienced by health agencies included changed patterns of drug use in their clients, increased aggressive incidents, changed numbers of clients accessing treatment services, and a need for more assistance from outside agencies. A strong evidence base for a range of drug treatment options, support of staff development in aggression management skills, and development of good interagency links between mental health, drug and alcohol, and law enforcement services would make health services better prepared for future changes in the drug use of their clients.

Topics: Health Planning; Health Services Needs and Demand; Heroin; Heroin Dependence; Humans; Illicit Drugs; New South Wales; Patient Acceptance of Health Care; Substance-Related Disorders

We recently described a reinstatement procedure that models relapse to drug abuse in cases where abstinence results from aversive consequences of drug use. The potential value of this punishment-based model of relapse depends on its sensitivity to relapse-inducing events that are ineffective in the widely used extinction-based model.. It is known that certain drugs can have anti-punishment effects, but these drugs have not been tested in the punishment-based reinstatement procedure. Therefore, the effects of the benzodiazepine, lorazepam, were examined using punishment-based and extinction-based reinstatement procedures.. Rats self-administered the opioid, remifentanil (4 microg/kg per infusion). Two punishment groups were trained with response-contingent footshock that suppressed baseline rates of responding to zero. In an extinction group, remifentanil delivery was discontinued, and baseline responding stabilized at a low rate (mean=0.06 responses/min). Lorazepam (0.08-10 mg/kg, IP) was given during test sessions with the shock contingency discontinued for both punishment groups. Remifentanil delivery was maintained during testing in one punishment group but not the other.. Lorazepam reinstated self-administration responding in both punishment groups but not in the extinction group. Priming injections of heroin reinstated responding in both the punishment and extinction groups, but combining heroin and lorazepam did not enhance reinstatement.. This is the first demonstration that a trigger for relapse may have different effects depending on whether aversive conditioning contributed to the achievement of abstinence. It may be important to consider potential anti-punishment effects of both abused drugs and therapeutic agents in the treatment of individuals with a history of drug abuse.

Topics: Analgesics, Opioid; Animals; Anti-Anxiety Agents; Conditioning, Operant; Dose-Response Relationship, Drug; Electroshock; Extinction, Psychological; Heroin; Heroin Dependence; Lorazepam; Male; Piperidines; Punishment; Rats; Rats, Sprague-Dawley; Remifentanil; Self Administration; Substance-Related Disorders

The role of heroin-related stimuli in motivating the resumption of heroin use is not fully understood.. The objective was to characterize the relative importance of drug-related contextual stimuli, discriminative stimuli (DS), or discrete conditioned stimuli (CSs) on drug seeking when rats were reintroduced into the operant context after withdrawal.. Nose-poke responding by male rats was reinforced with intravenous heroin (0.05 mg/kg per infusion, 4-h session daily) under a progressive ratio schedule of reinforcement for 14 days. Each session began with the illumination of a green light in the active hole that served as DS. Each earned heroin injection was paired with a 5-s compound cue light and the sound of the infusion pump that served as the discrete CSs.. Response rates of heroin seeking induced by the contextual stimuli were comparable to the average rates of responding during self-administration training, but rates induced by either DS or CSs were greater than those induced by the contextual stimuli alone (P<0.05). The responding induced by contingent presentations of CSs was higher than that of DS after extinction of instrumental behavior. The drug seeking induced by CSs can be maintained after 3 days extinction with DS in the original context, although the responding elicited by DS cannot be recovered after 3 days of extinction with CSs.. The relapse to drug seeking can be elicited separately by environmental cues, heroin-predictive DS, or discrete CSs in the same rat after withdrawal.

Topics: Analgesics, Opioid; Animals; Cues; Disease Models, Animal; Extinction, Psychological; Heroin; Heroin Dependence; Infusions, Intravenous; Male; Rats; Rats, Sprague-Dawley; Recurrence; Reinforcement Schedule; Self Administration; Signal Detection, Psychological; Substance Withdrawal Syndrome; Time Factors

Topics: Adult; Empathy; Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Male; Neonatal Abstinence Syndrome; Nurse-Patient Relations; Nurse's Role; Spirituality; Women's Health

A cohort of 495 heroin users, recruited for the Australian Treatment Outcome Study (ATOS), were re-interviewed at 12 months regarding suicide attempts over the follow-up period. The proportion who had attempted suicide in the 12 months since baseline was not significantly different from that reported in the 12 months preceding ATOS enrolment (12.2% versus 9.1%), and attempted suicide did not decline significantly in any of the index treatment groups. Among males, there was no significant reduction in attempted suicide (8.7% versus 8.1%). Among females, however, the proportion reporting an attempt declined significantly from 19.7 to 9.8%. Of those who reported suicidal ideation at baseline, 22.8% made an attempt over the follow-up period, as did 19.0% of those who had major depression. Large, and significant, declines in suicidal ideation (23.1% versus 6.9%) and major depression (25.5% versus 10.9%) occurred over the study period. Independent predictors of a suicide attempt over the follow-up period were: social isolation, having made an attempt in the preceding 12 months, suicidal ideation at baseline, a greater number of treatment episodes and higher levels of baseline polydrug use.

Topics: Adolescent; Adult; Analysis of Variance; Australia; Depressive Disorder; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Risk Factors; Sex Factors; Social Isolation; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Suicide, Attempted

Heroin overdose is a serious consequence of heroin use and one of the leading causes of premature death and illness in Australia. Despite considerable research effort little is known about the effects of transient changes in heroin user behaviour and the links to overdose. This research is the first to use a suitable methodology to allow such ephemeral changes and their effects on non-fatal heroin overdose to be examined.. A case-crossover design was used in which non-fatal heroin overdose survivors' recall of risk behaviours in the 12 hours prior to overdose (hazard period) was compared to their recall of risk behaviours in the 12 hours prior to a selected non-overdose heroin injection (control period).. A total of 155 participants were able to provide valid details of hazard and control periods. A dose-response relationship was observed between the self-reported amount of heroin used and likelihood of overdose (e.g. > AUD50, OR 12.97, 95% CI 2.54-66.31). The use of benzodiazepines (OR 28, 95% CI 3.81-205.79) or alcohol (OR 2.88, 95% CI 1.29-6.43), during the hazard period was related to overdose risk, but the effect of alcohol was attenuated by the effect of benzodiazepines. Shifting from private to public locations between control and hazard periods was also related to increased risk of overdose (OR 3.63, 95% CI 1.66-7.93).. We demonstrate the value of a new methodology to explore heroin overdose, as well as discussing its limitations and ways to overcome them in future. In terms of our findings, overdose prevention messages need to highlight the impact of these transient changes in behaviour and to emphasize the risks of using higher doses of heroin as well as continuing to emphasize the risks of combining heroin with other central nervous system (CNS) depressants. Safer environments for heroin use, such as injecting rooms, may also reduce the chances of overdose.

Topics: Adult; Australia; Case-Control Studies; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Overdose; Female; Health Behavior; Heroin; Heroin Dependence; Humans; Male; Prevalence; Risk Factors; Risk-Taking; Substance Abuse, Intravenous

Rats with a previous history of heroin self-administration were studied to assess interactions occurring between cannabinoids and opioids in an animal model of reinstatement of heroin-seeking behaviour. Rats were trained to self-administer heroin and after a long-term extinction were primed with one of the following non-contingent non-reinforced drug administrations: saline (or vehicle), heroin, synthetic cannabinoid CB(1) receptor agonists (WIN 55,212-2 or CP 55,940), opioid antagonist (naloxone) or CB(1) antagonist (SR 141716A), alone or in combination. After primings, lever-pressing activity was recorded and compared to those observed during previous phases of training and extinction. Results of this study showed that (i) priming injections of heroin (0.1 mg/kg) as well as CB(1) agonists WIN 55,212-2 (0.15 or 0.30 mg/kg) and CP 55,940 (0.05 or 0.1 mg/kg) completely restore heroin-seeking behaviour; (ii) primings of naloxone (1 mg/kg) and SR 141716A (0.3 mg/kg) had no effect when administered alone; (iii) heroin-induced reinstatement was fully prevented by pre-treatment with either naloxone or SR 141716A; (iv) pre-treatment with SR 141716A significantly reduced WIN 55,212-2 and CP 55,940 priming effects. These results suggest that cannabinoid CB(1) receptors play an important role in the mechanisms underlying relapse to heroin-seeking and depict CB(1) antagonists as possible therapeutic agents for use in the prevention of relapse to heroin abuse.

Topics: Animals; Behavior, Addictive; Benzoxazines; Conditioning, Operant; Cyclohexanols; Drug Interactions; Extinction, Psychological; Heroin; Heroin Dependence; Male; Morpholines; Naloxone; Naphthalenes; Piperidines; Pyrazoles; Rats; Rats, Inbred Strains; Receptor, Cannabinoid, CB1; Rimonabant; Self Administration

Topics: Administration, Inhalation; Ataxia; Brain; Brain Damage, Chronic; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Memory Disorders; Middle Aged; Narcotics; Nerve Fibers, Myelinated; Neurotoxicity Syndromes; Reflex, Abnormal

The incidence of heroin use among Manhattan arrestees interviewed by the Arrestee Drug Abuse Monitoring (ADAM) program remained around 20% from 1987 through 2001. However, the authors had expected a decline because the heroin injection epidemic peaked back in the 1960s and early 1970s. A detailed analysis found differences across race/ethnicity. Black arrestees born since 1955 (who came of age since the heroin injection epidemic) were much less likely to use heroin than those born between 1945 and 1954 (who came of age during the epidemic). Hispanic arrestees born since 1970 (but not those born between 1955 and 1969) were also less likely to use heroin, suggesting that the decline in heroin use started among Blacks before Hispanics. During the 1990s, sniffing replaced injecting as the predominant mode of heroin consumption for Black and Hispanic arrestees, even among older arrestees. In strong contrast, the prevalence of heroin use among White arrestees did not decline in the 1990s and injection was still their most popular method of consumption. The discussion highlights implications for further research and drug treatment.

Topics: Adult; Crime; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; New York City; Racial Groups

Topics: Drug Overdose; Heroin; Heroin Dependence; Humans; Illicit Drugs; Risk Factors

To examine the relationship between key patient variables and variation in naloxone dose (from the standard dose of 1.6 mg IMI) administered by ambulance paramedics in the prehospital management of heroin overdose.. A retrospective analysis of 7985 ambulance patient care records of non-fatal heroin overdose cases collected in greater metropolitan Melbourne. The main outcome measure was the dose of intramuscular naloxone required to increase the level of consciousness and the respiratory rate in patients presenting with suspected heroin overdose. Key patient variables influencing the dose that were recorded included: age, sex, initial patient presentation and reported concurrent alcohol use.. Multinomial logistic regression revealed that patients with higher levels of consciousness and respiratory rates on arrival of the paramedic crew were more likely to receive a less than standard dose of naloxone. Conversely, patients with lower levels of consciousness and low respiratory rates received greater than standard doses of naloxone for resuscitation. Patients who received greater than the standard dose of naloxone were 2.25 (95% CI, 1.83-2.77) times more likely to have been under the influence of alcohol when consuming the heroin that resulted in overdose.. The concurrent use of alcohol with heroin resulted in the use of greater than standard doses of naloxone by paramedics in resuscitating overdose patients. It is possible that the higher dose of naloxone is required to reverse the combined effects of alcohol and heroin. There was also a link between initial patient presentation and the dose of naloxone required for resuscitation. In light of these findings, it would appear that initial patient presentation and evidence of alcohol use might be useful guides as to providing the most effective dose of naloxone in the prehospital setting.

Topics: Adolescent; Adult; Aged; Alcohol-Related Disorders; Dose-Response Relationship, Drug; Drug Overdose; Emergency Medical Services; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Retrospective Studies

This paper uses a unique event, the Australian heroin shortage, to see whether an abrupt, substantial and sustained change in heroin supply had different effects on harms related to heroin use among younger and older heroin users.. Indicator data were examined by age group on the number of persons entering treatment for heroin and amphetamine dependence, arrests for heroin use/possession and number of drug related deaths in NSW, Australia. Data were analysed using times series analysis.. There was a 41% reduction in the number of new registrations for opioid pharmacotherapy per month among 25-34 year olds, and a 26% reduction among 15-24 year olds, but no apparent changes among older age groups. Similarly, reductions in the number of non-pharmacological heroin treatment episodes were most pronounced among younger age groups. There was a 49% reduction in the number of heroin possession/use offences among those aged 15-24 years, compared to declines of 31-40% among older age groups. Declines in heroin related deaths were greatest among 15-24 year olds (65% reduction). There was no change in other drug related deaths in any age group.. A reduction in heroin supply was followed by greater reductions in heroin related harms among younger than older people, across a number of outcome domains.

Topics: Adolescent; Adult; Age Distribution; Age Factors; Amphetamine-Related Disorders; Cause of Death; Criminal Law; Drug and Narcotic Control; Heroin; Heroin Dependence; Humans; Illicit Drugs; Law Enforcement; New South Wales; Patient Acceptance of Health Care

In humans, drug-associated stimuli can provoke heroin relapse during abstinence. In rats, cues paired with heroin self-administration reinstate heroin seeking in a relapse model. The neurobiological mechanisms involved in this reinstatement, however, are largely unknown. Here, we determined the effect of LY379268, an mGluR2/3 agonist that decreases evoked glutamate release, on cue-induced reinstatement of heroin seeking. Systemic injections of LY379268 attenuated reinstatement of heroin seeking induced by exposure to a discrete tone-light cue that was previously paired with heroin infusions during self-administration training. In contrast, LY379268 had no effect on heroin self-administration. Results indicate that glutamate plays an important role in cue-induced reinstatement of heroin seeking and suggest that mGluR2/3 agonists should be considered for the treatment of opiate relapse.

Topics: Amino Acids; Animals; Behavior, Animal; Bridged Bicyclo Compounds, Heterocyclic; Conditioning, Operant; Cues; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Extinction, Psychological; Heroin; Heroin Dependence; Male; Narcotics; Rats; Rats, Long-Evans; Self Administration

In early 2001 in Australia there was a sudden and dramatic decrease in heroin availability that occurred throughout the country that was evidenced by marked increases in heroin price and decreases in its purity.. This study examines the impact of this change in heroin supply on the following indicators of heroin use: fatal and non-fatal drug overdoses; treatment seeking for heroin dependence; injecting drug use; drug-specific offences; and general property offences. The study was conducted using data from three Australian States [New South Wales (NSW), Victoria (VIC) and South Australia (SA)].. Data were obtained on fatal and non-fatal overdoses from hospital emergency departments (EDs), ambulance services and coronial systems; treatment entries for heroin dependence compiled by State health departments; numbers of needles and syringes distributed to drug users; and data on arrests for heroin-related incidents and property-related crime incidents compiled by State Police Services. Time-series analyses were conducted where possible to examine changes before and after the onset of the heroin shortage. These were supplemented with information drawn from studies involving interviews with injecting drug users.. After the reduction in heroin supply, fatal and non-fatal heroin overdoses decreased by between 40% and 85%. Despite some evidence of increased cocaine, methamphetamine and benzodiazepine use and reports of increases in harms related to their use, there were no increases recorded in the number of either non-fatal overdoses or deaths related to these drugs. There was a sustained decline in injecting drug use in NSW and VIC, as indicated by a substantial drop in the number of needles and syringes distributed (to 1999 levels in Victoria). There was a short-lived increase in property crime in NSW followed by a sustained reduction in such offences. SA and VIC did not show any marked change in the categories of property crime examined in the study.. Substantial reductions in heroin availability have not occurred often, but in this Australian case a reduction had an aggregate positive impact in that it was associated with: reduced fatal and non-fatal heroin overdoses; reduced the apparent extent of injecting drug use in VIC and NSW; and may have contributed to reduced crime in NSW. All these changes provide substantial benefits to the community and some to heroin users. Documented shifts to other forms of drug use did not appear sufficient to produce increases in deaths, non-fatal overdoses or treatment seeking related to those drugs.

Topics: Adolescent; Adult; Crime; Drug Overdose; Health Behavior; Heroin; Heroin Dependence; Humans; Illicit Drugs; New South Wales; South Australia; Substance Abuse, Intravenous; Victoria

Topics: Australia; Heroin; Heroin Dependence; Humans; Illicit Drugs; United Kingdom; United States

Topics: Australia; Drug Overdose; Heroin; Heroin Dependence; Humans; Risk-Taking; Substance Abuse, Intravenous

Topics: Australia; Crime; Drug and Narcotic Control; Heroin; Heroin Dependence; Humans

Topics: Australia; Drug and Narcotic Control; Drug Overdose; Health Policy; Heroin; Heroin Dependence; Humans

To investigate spiral CT findings of pulmonary infection induced by intravenous injection of heroin.. The clinical data and spiral CT findings of 21 patients with pulmonary infection due to intravenous injection of heroin were analyzed retrospectively.. Pulmonary lesions were detected in all these cases in the initial examination by spiral CT plain scan, including pneumatocele in 13 (61.9%), pulmonary cavity in 13 (61.9%), pulmonary consolidation in 15 (71.4%), and plural lesions in 8 cases (38.1%) of which 7 (33.3%) had plural effusion and 1 (0.48%) had encapsulated hydropneumothorax. Three cases had only one of the lesions and 18 had at least 2 of them. The CT images in each case were compared with X-ray film, and the latter displayed abnormalities in 20 cases (95.2%). X-ray failed to detect the lesions in 1 case (4.8%), in which pneumatocele was found in CT images.. The pulmonary lesions of pulmonary pneumatocele, cavity, consolidation, and plural lesions are specific CT manifestations of hematogenous pulmonary suppurative infection induced by intravenous injection of heroin.

Topics: Adult; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Pneumonia; Retrospective Studies; Tomography, Spiral Computed

We sought to identify prevalence and predictors of heroin-related overdose among young injection drug users (IDU).. A total of 795 IDU under age of 30 years were interviewed in four neighbourhoods in San Francisco, California, USA. Participants were recruited as part of a broader study of HIV, hepatitis B and C among injecting drug users in San Francisco using street outreach and snowball techniques. Independent predictors of recent heroin overdose requiring intervention were determined using regression analysis.. Of 795 injecting drug users under age of 30 years, 22% (174/795) of participants reported a heroin overdose in the last year. In stepwise multiple logistic regression, independent predictors of recent heroin overdose were lifetime incarceration exceeding 20 months (odds ratio (OR) = 2.99, 95% confidence interval (CI) = 1.52-5.88); heroin injection in the last 3 months (OR = 4.89, 95% CI = 2.03-11.74); cocaine injection in the last 3 months (OR = 1.67, 95% CI = 1.14-2.45); injection of heroin mixed with methamphetamine in the last 3 months (OR = 1.74, 95% CI = 1.15-2.65); ever tested for hepatitis B or C (OR = 1.66 per year, CI = 1.09-2.54) and ever having witnessed another person overdose (OR = 2.89, 95% CI = 1.76-4.73).. Individuals with high levels of incarceration are at great risk of overdose, and prison or jail should be considered a primary intervention site. Further research on the role of cocaine and amphetamine in heroin-related overdose is indicated.

Topics: Acute Disease; Adolescent; Adult; California; Catchment Area, Health; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Methamphetamine; Prevalence; Prisoners; Resuscitation; Substance Abuse, Intravenous; Surveys and Questionnaires

Toxic leukoencephalopathy has been described with inhalation and intravenous consumption of heroin and cocaine. The clinical picture varies widely but the imaging and histological features are characteristic. Magnetic resonance imaging (MRI) typically reveals diffuse bihemispheric white matter lesions. Histologically there is extensive spongiform degeneration of the cerebral white matter.. To report two cases of fatal toxin associated leukoencephalopathy, along with detailed imaging and neuropathological studies.. MRI revealed diffuse white matter changes. Histologically there was widespread confluent vacuolar degeneration of the deep white matter. In both cases, there was sparing of the brain stem and cerebellar white matter. There was evidence of severe and extensive axonal injury.. This pattern of radiological involvement and histological findings has not previously been reported and may reflect the presence of a yet unidentified impurity.

Topics: Adult; Brain; Brain Stem; Cerebellum; Cerebral Cortex; Cocaine; Cocaine-Related Disorders; Disease Progression; Dominance, Cerebral; Fatal Outcome; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Nerve Degeneration; Nerve Fibers; Neurologic Examination; Neurotoxicity Syndromes

Discriminating right from left is an everyday cognitive ability. Repeated exposure to certain drugs, such as heroin, can produce poor performance on many cognitive tasks. However, it is yet unclear whether drug abuse impairs the ability of right-left discrimination.. The aim of the present study is to examine whether the spatial ability measured by the right-left discrimination task can be affected by heroin abuse and whether such drug effect, if it exists, is gender related.. A paper-and-pen test was used. The test consists of line drawings of a person with no arm, one arm, or both arms crossing the vertical body axis of the figure. The line drawings are viewed from the back, from the front, or randomly alternating between the back and front drawings. The subjects' task is to mark which is the right or left hand in the figure as fast as possible.. A main finding in this study was that the ability to discriminate between left and right in visual space was impaired in heroin-dependent patients. Especially, heroin-dependent females performed poorer than control females in all conditions but heroin-dependent males only performed poorly in part of conditions.. Recent heroin abuse impairs the ability of right-left discrimination and such impairment is gender related: heroin-dependent females demonstrated greater performance deficits than males.

Topics: Adult; Discrimination Learning; Female; Functional Laterality; Heroin; Heroin Dependence; Humans; Male; Orientation; Psychomotor Performance; Sex Factors

Heroin is rapidly metabolized to morphine that in turn is transformed in morphine-3-glucuronide (M3G), an inactive metabolite, and morphine-6-glucuronide (M6G), a potent mu-opioid receptor (MOR) agonist. We have found that heroin addicts exhibit higher M6G/M3G ratios relative to morphine-treated control subjects. We have also shown that heroin-treated rats exhibit measurable levels of M6G (which is usually undetectable in this species) and reduced levels of M3G.. We investigated the role of MOR in these effects of heroin, by examining the effects of methadone, a MOR agonist, and of naltrexone, a MOR antagonist, on morphine glucuronidation. We also investigated the effects of alcohol, which is known to alter drug metabolism and is frequently coabused by heroin addicts.. Morphine glucuronidation was studied in liver microsomes obtained from rats exposed daily for 10 days to saline, heroin (10 mg/kg, i.p.), naltrexone (20-40 mg/kg, i.p.), heroin + naltrexone (10 mg/kg+20-40 mg/kg, i.p.), methadone (5-20 mg/kg, i.p.), or 10% ethanol.. Heroin induced the synthesis of M6G and decreased the synthesis of M3G. Naltrexone exhibited intrinsic modulatory activity on morphine glucuronidation, increasing the synthesis of M3G via a low-affinity/high-capacity reaction characterized by positive cooperativity. The rate of M3G synthesis in the heroin + naltrexone groups was not different from that of the naltrexone groups. Methadone and ethanol induced a modest increase in M3G synthesis and had no effect on M6G synthesis.. The effects of heroin on morphine glucuronidation are not shared by methadone or alcohol (two drugs that figure prominently in the natural history of heroin addiction) and do not appear to depend on the activation of MOR.

Topics: Animals; Ethanol; Heroin; Heroin Dependence; Male; Methadone; Microsomes, Liver; Morphine; Morphine Derivatives; Naltrexone; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu

Accidental intrarterial injections are not uncommon in medical treatments. This is also true for uncontrolled injections by drug-addicts. Since 2002 a number of 600 heavy opiate addicts in Germany are substituted in a country-wide study with pure diacetylmorphine (Heroine). We report the course and outcome of three cases of accidental intraarterial injections of pure diacetylmorphine under controlled conditions. After initial symptoms of vasospasms, all cases were without symptoms within one hour and no obvious loss of tissue was observed. After discussing the literature about medical literature and treatment options in intraarterial injections it is concluded, that the cause of major complications after intraarterial injections may not be the pure diacetylmorphine but additional substances in impure "street-heroin" samples.

Topics: Adult; Hepatitis C; Heroin; Heroin Dependence; HIV Infections; Humans; Injections, Intra-Arterial; Male

In early 2001, Australia experienced a sudden, dramatic and sustained decrease in heroin availability that was accompanied by sharp increases in price and decreases in street level purity--the so-called "heroin shortage". These unprecedented changes occurred in a context of widespread treatment availability, which made it possible for the first time to examine the impact of a sharp reduction in heroin supply in New South Wales (NSW) on entry to and adherence with treatment for heroin dependence. Given the evidence of drug substitution by some users, the current paper also examines the effects of the shortage on entry to treatment for other forms of drug dependence.. Interrupted time-series analysis of the number of persons entering opioid pharmacotherapy and other treatment modalities in NSW for heroin dependence and for the treatment for other types of drug dependence.. The heroin shortage was associated with a reduction in the number of younger persons entering opioid pharmacotherapy. There was a dramatic decrease in the number of persons entering heroin withdrawal or "assessment only" treatment episodes. There appear to have been small improvements in adherence to and retention in heroin treatment after the reduction in heroin supply. Relatively small increases were observed in numbers being treated for cocaine dependence.. In the context of good treatment provision, a reduction in heroin supply appeared to produce modest improvements in intermediate outcomes. Supply and demand reduction measures, when both are implemented successfully, may be complementary.

Topics: Cocaine; Female; Heroin; Heroin Dependence; Humans; Male; Methamphetamine; New South Wales; Patient Compliance; Patient Dropouts; Substance Abuse Treatment Centers; Time Factors

A major goal of heroin-assisted treatment in Switzerland has been to reduce the drug-related mortality of heroin users. Therefore, a continuous monitoring of deaths under treatment is essential.. To assess mortality of participants in heroin-assisted treatment in Switzerland over a 7-year period from 1994 to 2000, and to compare this mortality to the general population and to other populations of opioid users, as reported in the literature.. Estimation of person years under heroin-assisted treatment from the complete case registry of heroin-assisted treatment in Switzerland. Estimation of standardized mortality ratios comparing the population in treatment to the Swiss population (standardized to the year 2000).. Over the 7-year period, the crude death rate of patients in heroin-assisted treatment, and including one month after discharge from treatment, was 1% per year. The standardized mortality ratio for the entire observation period was 9.7 (95% C.I. 7.3-12.8), with females having higher standardized mortality ratios (SMR 17.2) than males (SMR 8.4). There was no clear time trend.. Mortality in heroin-assisted treatment was low compared to the mortality rate of Swiss opioid users 1990s (estimated to be between 2.5 and 3%). It was also low compared to mortality rates of opioid users in other maintenance treatments in other countries as reported in the literature. The SMR was also lower than that reported in the only meta-analysis in the literature: 13.2 (95% C.I. 12.3-14.1). The low mortality rate is all the more noteworthy as heroin-assisted treatment in Switzerland included only refractory opioid addicts with existing severe somatic and/or mental problems.. No conflicts of interest declared.

Topics: Cause of Death; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Narcotics; Sex Factors; Substance Abuse Treatment Centers; Switzerland

Drug users frequently witness the nonfatal and fatal drug overdoses of their peers, but often fail to intervene effectively to reduce morbidity and mortality. We assessed the circumstances of witnessed heroin-related overdoses in New York City (NYC) among a predominantly minority population of drug users. Among 1184 heroin, crack, and cocaine users interviewed between November 2001 and February 2004, 672 (56.8%) had witnessed at least one nonfatal or fatal heroin-related overdose. Of those, 444 (67.7%) reported that they or someone else present called for medical help for the overdose victim at the last witnessed overdose. In multivariable models, the respondent never having had an overdose her/himself and the witnessed overdose occurring in a public place were associated with the likelihood of calling for medical help. Fear of police response was the most commonly cited reason for not calling or delaying before calling for help (52.2%). Attempts to revive the overdose victim through physical stimulation (e.g., applying ice, causing pain) were reported by 59.7% of respondents, while first aid measures were attempted in only 11.9% of events. Efforts to equip drug users to manage overdoses effectively, including training in first aid and the provision of naloxone, and the reduction of police involvement at overdose events may have a substantial impact on overdose-related morbidity and mortality.

Topics: Adolescent; Adult; Crisis Intervention; Drug Overdose; Emergency Medical Services; Emergency Treatment; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; New York City; Peer Group; Prevalence

Conditioned environmental stimuli are known to be important determinants of drug seeking behavior. c-Fos, the protein product of the protooncogene c-Fos, is expressed in neurons when there are drug-associated cue-induced drug-seeking behaviour. Therefore, its expression could serve as a marker of regional neuronal activation. Using an extinction/reinstatement paradigm of relapse animal model, we trained Sprague-Dawley rats to nose-poke for i.v. heroin (0.05 mg/kg/infusion) either daily for 4h or 25 infusions for 14 consecutive days. We then tested these animals for cue-evoked heroin-seeking behavior after abstinence from self-administration of heroin for 14 days. Expression of c-Fos was examined in the lateral habenula (LHb), a region important for conveying information between the limbic forebrain and midbrain. Findings showed that heroin-associated conditioned stimuli could induce robust heroin-seeking behavior that was associated with increased c-Fos immunoreactivity in the medial part of the LHb. This observation suggests the involvement of the LHb in mediating drug cue-induced heroin-seeking behavior after abstinence from self-administration of heroin.

Topics: Animals; Behavior, Addictive; Conditioning, Psychological; Extinction, Psychological; Habenula; Heroin; Heroin Dependence; Male; Narcotics; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley

In recent years, there has been an increase in cocaine-related deaths at the Department of Legal Medicine and Public Health of Pavia, probably reflecting the rising trend in cocaine use in Western Europe. Deaths from cocaine alone have increased from 6 cases in 1979-1991 (1.5% of drug-of-abuse deaths) to 13 in 1992-2002 (3.2%) and comparing the same periods, heroin-related deaths (HRDs) involving cocaine more than doubled from 8 (1.9%) to 22 (5.4%). In an attempt to investigate the role of cocaine in HRDs, acute narcotic death cases testing positive for cocaine use (blood cocaine or metabolite concentration >0.01 mg/l, COC+) were examined. Only cases from 1997 to 2001 were considered as in this period all data were obtained using the same analytical procedures (free morphine and total morphine by DPC Coat-A-Count radioimmunoassay before and after enzymatic hydrolysis, cocaine and metabolites in blood by SPE, TMS derivatization and gas chromatography-mass spectrometry (GC-MS)). The median, minimum and maximum concentrations of free morphine in blood (FM) and total morphine in blood (TM), urine (UM) and bile (BM) in the COC+ group (n = 9) were compared with those calculated in the group of "pure" HRDs (no other drugs detected in blood, COC-, n = 30). Differences among the medians in the two groups were statistically evaluated using the two-tailed Mann-Whitney U-Test. Statistical analysis was also carried out including in both groups cases with a blood alcohol concentration (BAC) > 20 mg/L (COC+, n = 19; COC-, n = 76). For the COC+ group, median TM was lower (0.32 mg/l versus 0.90 mg/l, P = 0.0214), median FM was lower, but not statistically significant (0.08 mg/l versus 0.28 mg/l, P = 0.1064), FM/TM ratio was similar (0.33 and 0.35), UM was also similar (21.0 mg/l and 18.0 mg/l), and BM was higher (90.0 mg/l versus 49.0 mg/l, P = 0.0268). Similar comparison results were obtained by repeating statistical analyses after including in the two groups cases with positive BAC. The picture observed for HRD cases involving cocaine is very different from what was previously observed for HRD cases involving ethanol [A. Polettini, A. Groppi, M. Montagna, The role of alcohol abuse in the etiology of heroin related deaths: evidence for pharmacokinetic interactions between heroin and alcohol, J. Anal. Toxicol. 23 (1999) 570-576], and updated with more recent data; in the high-ethanol (HE, BAC > 1000 mg/l) group, TM was lower than in the low-ethanol (LE, BAC

Topics: Adolescent; Adult; Bile; Central Nervous System Depressants; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Drug Interactions; Ethanol; Female; Forensic Medicine; Heroin; Heroin Dependence; Humans; Male; Morphine; Narcotics; Substance Abuse Detection

A sample of 442 heroin users (394 injecting heroin users: IHU, 48 non-injecting heroin users: NIHU) recruited for the Australian Treatment Outcome Study were reinterviewed at 12 months after entrance to treatment for heroin dependence. Route of administration was stable over the follow-up period with 4% of NIHU having made a transition to heroin injecting, and 0.3% of IHU having made a transition to non-injecting. Given the clinical profile of NIHU presented in the literature, it might be expected that they would exhibit better treatment retention and 12-month outcomes than IHU. At 12 months, however, there were no differences between NIHU and IHU in heroin use, heroin dependence symptoms, polydrug use, criminality, current self-reported physical health or psychopathology. The only group differences at 12 months were that NIHU were more likely to be employed and had fewer injection-related problems. It is concluded that, among those presenting for treatment, route of administration is not an indicator of likely outcome.

Topics: Comorbidity; Depressive Disorder, Major; Employment; Follow-Up Studies; Health Status; Heroin; Heroin Dependence; Humans; Ill-Housed Persons; Psychiatric Status Rating Scales; Smoking; Smoking Prevention; Social Adjustment; Substance Abuse, Intravenous; Treatment Outcome

The current study aimed to model the effect of Australia's first Medically Supervised Injecting Centre (MSIC) on acquisitive crime and loitering by drug users and dealers. The effect of the MSIC on drug-related property and violent crime was examined by conducting time series analysis of police-recorded trends in theft and robbery incidents, respectively. The effect of the MSIC on drug use and dealing was examined by (a) time series analysis of a special proxy measure of drug-related loitering; (b) interviewing key informants; and (c) examining trends in the proportion of Sydney drug offences that were recorded in Kings Cross. There was no evidence that the MSIC trial led to either an increase or decrease in theft or robbery incidents. There was also no evidence that the MSIC led to an increase in 'drug-related' loitering at the front of the MSIC after it opened, although there was a small increase in 'total' loitering (by 1.2 persons per occasion of observation). Trends in both 'drug-related' and 'total' loitering at the front of the MSIC steadily declined to baseline levels, or below, after it opened. There was a very small but sustained increase in 'drug-related' (0.09 persons per count) and 'total' loitering (0.37 persons per count) at the back of the MSIC after it opened. Key informant interviews noted an increase in loitering across the road from the MSIC but this was not attributed to an influx of new users and dealers to the area. There was no increase in the proportion of drug use or drug supply offences committed in Kings Cross that could be attributed to the opening of the MSIC. These results suggest that setting up an MSIC does not necessarily lead to an increase in drug-related problems of crime and public loitering.

Topics: Australia; Crime; Criminal Law; Heroin; Heroin Dependence; Humans; Needle-Exchange Programs; Social Problems; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Urban Population

Using c-Fos protein immunohistochemistry we previously demonstrated various sites of activation in the rat forebrain according to the animal's drug history. This study originates from a more detailed evaluation ex-post of the same specimens. A discrete number of c-Fos protein immunoreactive nuclei could be observed in some circumventricular organs, including the vascular organ of terminal lamina (OVLT) and subfornical organ (SFO) and in the nucleus of solitary tract near the area postrema, but only in specimens from sensitized rats. We therefore suggest that repeated drug injections activate the normally low drug metabolizing enzyme activity in the circumventricular organs thus implicating these organs in the complex mechanisms underlying behavioral sensitization.

Topics: Animals; Area Postrema; Disease Models, Animal; Enzyme Activation; Enzymes; Heroin; Heroin Dependence; Hypothalamus; Immunohistochemistry; Narcotics; Neural Pathways; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Solitary Nucleus; Subfornical Organ; Up-Regulation

For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC-MS/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay was extended with the detection of cocaine, its metabolites benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were used as internal standards. The sample pre-treatment consisted of solid phase extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic separation was performed at 25 degrees C on a reversed phase Zorbax column with a gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile. The run time was 15 min. MS with relatively mild electrospray ionisation under atmospheric pressure was applied. The triple quadrupole MS was operating in the positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 5-500 ng/mL for all analytes. The total recovery of heroin varied between 86 and 96% and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay accuracy and precision of all analytes were always within the designated limits (< or =20% at lower limit of quantification (LLQ) and < or =15% for other samples). This specific and sensitive assay was successfully applied in pharmacokinetic studies with medically prescribed heroin and toxicological cases.

Topics: Administration, Inhalation; Chromatography, High Pressure Liquid; Cocaine; Codeine; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Time Factors

In preparation for a treatment program concerning the medical coprescription of heroin and methadone to treatment-resistant addicts in the Netherlands, we studied a novel strategy for monitoring co-use of illicit (nonprescribed) heroin. A deuterated analogue of heroin was added (1:20) to pharmaceutical, smokable heroin (a powder mixture of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate), to be used by inhalation after volatilization ("chasing the dragon"). Plasma and urine samples were collected from nine male patients who had used pharmaceutical, smokable heroin during a four-day stay in a closed clinical research unit, and these samples were analyzed by liquid chromatography coupled with tandem mass spectrometry. Ratios of deuterated and undeuterated diacetylmorphine and 6-acetylmorphine (MAM/MAM-d3) in plasma and urine were calculated from peak areas of these substances in the respective chromatograms. The MAM/MAM-d3 ratios in plasma and urine were normally distributed (with small standard deviations) and independent from concentrations of 6-acetylmorphine and from time after use of pharmaceutical heroin. A MAM/MAM-d3 ratio in urine above 32.8 was considered indicative of co-use of illicit heroin, and this value was associated with a false-positive rate of only 1% (95% confidence interval: -1 to 3%). The MAM/MAM-d3 ratio was detectable in urine for 4-9.5 h after use of pharmaceutical, smokable heroin. Addition of stable, isotopically labelled heroin to pharmaceutical, smokable heroin is considered to be a feasible strategy for the detection of co-use of illicit heroin by patients in heroin-assisted treatment.

Topics: Administration, Inhalation; Biomarkers; Chromatography, Liquid; Heroin; Heroin Dependence; Humans; Male; Mass Spectrometry; Reference Standards; Sensitivity and Specificity; Substance Abuse Detection

Measurement of plasma methadone concentration to investigate the rate of clearance of methadone prescribed for heroin dependence in the first, second and third trimesters of pregnancy. A secondary objective was to evaluate the outcome of pregnancy.. Longitudinal within subject study of nine pregnant opioid dependent subjects prescribed methadone at the Leeds Addiction Unit, an outpatient community based treatment centre. Plasma concentration versus time data for methadone was collected during each trimester and post-partum for our subjects. Data was available for the first and second trimesters for 4/9 cases. All but one of the subjects provided data during the third trimester and data post-partum was collected from three respondents. Measurements of methadone levels in plasma were carried out using high performance liquid chromatography (HPLC).. Trough mean plasma methadone concentrations reduced as the pregnancies progressed from 0.12 mg/L (first trimester) to 0.07 mg/L (third trimester). The weight-adjusted clearance rates gradually increased from a mean of 0.17 to 0.21 L/hr/kg during pregnancy, although patterns differed substantially between the nine women. An assessment of relative clearance of methadone using two patients for whom we have had all three CL values (trimester 1-3) demonstrated notable change of CL (P = 0.056) over time. Eight of our subjects delivered (3 males), within two weeks of their due date the ninth (male) was premature (21 days). The mean length of gestation was 39.7 weeks (SD = 10 days) and none of the neonates met criterion for 'low birth weight' mean = 3094, SD = 368 g). Five neonates spent time (0.5-28 days) in a special care baby unit (SCUBU) and 4 of these displayed signs of methadone withdrawal.. General Practitioners and hospital doctors should recognise the significant benefits of prescribing methadone for heroin-dependent women during pregnancy. We recommend that if a pregnant opioid user complains of methadone withdrawal symptoms (i.e. that the methadone dose does not "hold" them) the prescribing clinician takes this observation seriously and considers a more detailed assessment. Further work on key factors undergoing changes during pregnancy accounting for differences in methadone metabolism in the mother, fetus and neonate are required.

Topics: Adolescent; Adult; Area Under Curve; Chromatography, High Pressure Liquid; Female; Heroin; Heroin Dependence; Humans; Metabolic Clearance Rate; Methadone; Narcotics; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Relapse to drug taking is triggered by stimuli previously associated with consumption of drugs of misuse (cues) and involves brain systems controlling motivated behaviour towards natural reinforcers. In this study, we aimed to identify and compare neuronal pathways in corticostriatal systems that control conditioned heroin or natural reward (sucrose) seeking. To that end, rats were trained to self-administer heroin or sucrose in association with an identical compound cue. After more than 3 weeks of abstinence during extinction training, cue exposure robustly reinstated heroin and sucrose seeking, but induced distinct and even opposing changes in the expression of the neuronal activation marker zif268 in the prelimbic cortex and striatal complex, respectively. Because in the prelimbic area zif268 expression was enhanced during cue-induced heroin seeking but unaffected during sucrose seeking, a pharmacological intervention was aimed at this prefrontal region. Injection of a GABA agonist mixture within the prelimbic area enhanced conditioned heroin seeking, but had no effect on conditioned sucrose seeking. Our findings suggest a differential role of the prelimbic area and the striatum in the persistence of heroin vs. sucrose seeking following long-term extinction.

Topics: Analysis of Variance; Animals; Behavior, Animal; Cell Count; Cerebral Cortex; Conditioning, Operant; Corpus Striatum; Diagnostic Imaging; Early Growth Response Protein 1; Extinction, Psychological; gamma-Aminobutyric Acid; Gene Expression Regulation; Heroin; Heroin Dependence; Immunohistochemistry; Male; Narcotics; Rats; Rats, Sprague-Dawley; Self Administration; Sucrose; Sweetening Agents

Topics: Analgesics, Opioid; England; Heroin; Heroin Dependence; Humans; Methadone

The relationship between treatment exposure, drug use, psychosocial variables and non-fatal heroin overdose was examined among a cohort of 495 heroin users, re-interviewed at 12 months. The 12-month overdose rate declined from 24% to 12%, and the proportion administered naloxone declined from 15% to 7%. There were significant reductions in overdose among those who entered maintenance therapies (22% to 4%) and residential rehabilitation (33% vs. 19%) at baseline, but not among those who entered detoxification or were not entering treatment. The total number of treatment days received over the follow-up period was associated independently with a reduced risk of overdose. Each extra treatment day was associated with a 1% reduction in risk of overdose over the follow-up period. By contrast, more treatment episodes were associated with an increased risk of overdose (OR 1.62). Other independent predictors of overdose over follow-up were more extensive polydrug use (OR 1.40), and having overdosed in the year preceding the study (OR 7.87).

Topics: Adult; Australia; Cohort Studies; Demography; Diagnostic and Statistical Manual of Mental Disorders; Drug Overdose; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Residential Treatment; Treatment Outcome

To make technical standard of acupuncture manipulation for acupuncture treatment of heroin withdrawal syndrome.. Two hundred and twenty cases of heroin withdrawal syndrome were randomly divided into an acupuncture group of 111 cases and a control group of 109 cases. They were respectively treated with acupuncture and oral administration of lofexidine hydrochloride, and their therapeutic effects were observed.. The heroin dependence (acute stage) were effectively withdrawn in the two groups. The treatment group in change of total scores for withdrawal symptoms before and after treatment, the total scores for withdrawal symptoms at the 4th and 5th days, treatment of insomnia and the score for self-Hamilton Anxiety Scale and the score after at the 4th day was superior to the control group (P < 0.05, P < 0.01, P < 0.001).. Acupuncture has a satisfactory, rapid, safe and reliable clinical therapeutic effect.

Topics: Acupuncture Therapy; Anxiety; Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

Buprenorphine is a narcotic analgesic used in the treatment of moderate-to-severe pain. In Italy, buprenorphine is now being used as an alternative in the therapeutic treatment of heroin abusers. Even if confirmation methods are needed for identification and quantitation, a rapid and sensitive test, such as an immunoassay, is essential for screening. We evaluated the Buprenorphine One-step ELISA test (designed for serum specimens) for the qualitative determination of buprenorphine in other matrices, such as urine, saliva and hair.

Topics: Buprenorphine; Enzyme-Linked Immunosorbent Assay; Hair; Heroin; Heroin Dependence; Humans; Italy; Narcotic Antagonists; Reference Standards; Saliva; Sensitivity and Specificity; Serum; Substance Abuse Detection; Urine

Opioids and antidepressants are frequently used for the treatment of various pain conditions. A combination of both drug classes may be more effective than either treatment alone, and combined treatment with an antidepressant may result in an opiate-sparing effect. Although it has been shown that antidepressants can attenuate self-administration of psychomotor stimulant and depressant drugs, it is not known whether they also attenuate self-administration of opiates. To determine whether venlafaxine, a serotonin/noradrenaline reuptake inhibitor with antidepressive and analgesic properties, affects acquisition and maintenance of intravenous heroin self-administration in rats, male Long-Evans rats were trained to press a lever in order to receive heroin (0.05 mg/kg/infusion) under a fixed ratio or a progressive ratio schedule. A control group was trained in a fixed ratio food-reinforced operant procedure. The effect of venlafaxine on operant responding for heroin and food was assessed both during acquisition and, in separate groups of rats, during maintenance (i.e., after acquisition) of self-administration behaviour. Daily treatment with venlafaxine (10 mg/kg i.p.) before the operant session attenuated the acquisition of responding for heroin, but not for food. However, when tested during the maintenance phase in rats showing stable responding, acute treatment with venlafaxine only marginally affected operant responding for heroin under a fixed ratio:10 schedule of reinforcement, and neither acute nor subchronic (once daily during 4 weeks) venlafaxine treatment affected responding under a progressive ratio schedule. Thus, daily treatment with an antidepressant attenuates the acquisition of heroin self-administration in a behaviourally specific manner, while having only marginal effects on maintenance of heroin self-administration.

Topics: Animals; Behavior, Addictive; Behavior, Animal; Conditioning, Operant; Cyclohexanols; Feeding Behavior; Heroin; Heroin Dependence; Male; Rats; Rats, Long-Evans; Reinforcement Schedule; Selective Serotonin Reuptake Inhibitors; Self Administration; Substance Abuse, Intravenous; Venlafaxine Hydrochloride

Topics: Adult; Heroin; Heroin Dependence; Humans; Magnetic Resonance Spectroscopy; Male; Neurotoxicity Syndromes

The use of illicit drugs, specifically heroin and cocaine, complicates trauma patient management and consumes extensive hospital resources. This paper focuses on heroin- and cocaine-related injuries observed by physicians at Detroit Receiving Hospital, a large urban Level I trauma center. The pharmaceutical effects, mode of administration, and the manner in which these drugs affect diagnosis and treatment of injuries are documented and discussed. Specific drug-related complications associated with overdose, soft-tissue infections, bacterial endocarditis (therapy resistant), vascular thromboses, vascular aneurysms, vasoconstriction, stroke, cardiac arrhythmias, muscle ischemia, and solid-organ abscesses are also analyzed. Illicit drug use significantly complicates initial diagnosis and trauma management and is associated with severe adverse pathophysiologic effects. Currently, prevention efforts, such as interventions in trauma centers, should be considered as the most efficient and feasible way to prevent injury recidivism in this patient population. We also conclude that legislative change may be the answer in reducing or preventing the horrendous problems caused by illicit drugs.

Topics: Cocaine; Cocaine-Related Disorders; Disease; Heroin; Heroin Dependence; Humans; Illicit Drugs; Patient Care; Wounds and Injuries

Crack cocaine use is more associated with impulsivity and a propensity to take risks than heroin use, yet no studies have examined this relationship in the absence of acute drug effects. The current study examined impulsivity (using the Delay Discounting Task) and risk-taking propensity (using the Balloon Analogue Risk Task) across independent groups of primary crack cocaine users with minimal heroin use (n = 16) and primary heroin users with minimal crack cocaine use (n = 11) in residential treatment, with all participants drug abstinent during participation. Crack cocaine users evidenced greater levels of impulsivity and risk-taking propensity, with only the difference in impulsivity persisting after controlling for age and gender. These data hold potential theoretical importance in understanding differences between crack cocaine and heroin users, as the findings cannot be attributed solely to acute pharmacological drug effects.

Topics: Age Factors; Analysis of Variance; Behavioral Research; Cocaine-Related Disorders; Crack Cocaine; District of Columbia; Female; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Male; Residential Treatment; Reward; Risk-Taking; Sex Factors; Surveys and Questionnaires; Urban Population

The clinical implementation and evaluation of heroin substitution programmes have been confounded by the lack of objective and validated biomarkers for illicit heroin use in patients prescribed pharmaceutical heroin. This study examined the capacity to detect illicit heroin use by gas chromatography-mass spectrometry (GC-MS) analysis of urine samples for the presence of opium impurities common to illicit, but not pharmaceutical heroin.. To characterize the diagnostic properties of the metabolites of noscapine and papaverine in comparison to morphine as a gold-standard marker of illicit heroin use; and to examine the relationships between the self-reported time since most recent heroin use and the detection of these opioids in urine.. A cross-sectional study of 52 opioid-dependent patients in treatment (not prescribed heroin), who self-reported illicit heroin use within the preceding 2 weeks. Self-report data regarding recent drug use and a urine sample were collected. GC-MS analyses of urines were conducted and reported by laboratory staff blinded to self-report data.. The metabolites of papaverine (hydroxypapaverine and dihydroxypapeverine) were found to have high sensitivity, specificity and negative predictive values as markers for illicit heroin use compared to the 'gold-standard' morphine. Other opioids, including 6-mono-acetylmorphine (6-MAM), codeine and noscapine metabolites (e.g. meconine) were less adequate in detecting heroin use.. GC-MS detection of papaverine metabolites in urine appears to be suitable method of identifying illicit heroin use for clinical and research purposes.

Topics: Adult; Cross-Sectional Studies; Female; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Substance Abuse Detection; Treatment Outcome

3-O-Methylnaltrexone (3-MNTX), a putative antagonist of morphine-6-beta-d-glucuronide (M6G) receptors, has been reported to block the behavioral effects of heroin at doses that do not block those of morphine, suggesting that M6G receptors may play a unique role in the addictive properties of heroin. This study investigated the effects of 3-MNTX in monkeys trained to discriminate i.v. heroin from vehicle or to self-administer i.v. heroin under a progressive-ratio schedule. Additional in vitro studies determined the effects of 3-MNTX and reference drugs on adenylyl cyclase activity in caudate-putamen membranes of monkeys and rats. In drug discrimination experiments, heroin, morphine, and M6G substituted for heroin in all subjects, whereas 3-MNTX substituted for heroin in one-half the monkeys tested. In these latter monkeys, the effects of 3-MNTX were antagonized by naltrexone, and pretreatment with 3-MNTX enhanced the effects of heroin, M6G, and morphine, indicative of micro-agonist activity. In monkeys showing no substitution of 3-MNTX for heroin, 3-MNTX antagonized the effects of heroin, M6G, and morphine. In self-administration experiments, heroin and 3-MNTX maintained injections per session significantly above those maintained by vehicle when the initial response requirement (IRR) was low; only heroin maintained significant self-administration when the IRR was high. In vitro, 3-MNTX inhibited adenylyl cyclase activity in both monkey and rat brain membranes. The degree of inhibition produced by 3-MNTX was less than that produced by the full agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO). The results suggest that 3-MNTX functions primarily as a partial agonist at micro-receptors in monkeys and do not support a singular role for M6G receptors in the abuse-related effects of heroin.

Topics: Adenylyl Cyclases; Animals; Cocaine; Discrimination Learning; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Heroin; Heroin Dependence; Macaca mulatta; Male; Morphine; Morphine Derivatives; Naltrexone; Narcotics; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Self Administration

Within the guidelines of the research programme on medical prescription of narcotics for opioid addicts (PROVE), heroin, morphine, and methadone were prescribed to heavily opioid addicted individuals in Switzerland since 1994. This contribution analyses the course of dose levels during the treatment period.. Naturalistic description of consumed dosages per day and month.. The study describes the dosages prescribed to all individuals who began outpatient treatment in the PROVE programme in Switzerland between 1994 and 1996.. Consumed amount of narcotics per day and the course of dosage of injectable heroin in different treatment regimes.. Heroin was the most frequently prescribed narcotic. Of all consumption days, heroin had been applied in 77% as injection and in 9% in a smokeable form. The mean daily dosage was 474 mg for intravenous application and 993 mg for the smokeable form. Second most frequent was the prescription of oral methadone, in most cases in combination with heroin. The mean amount of daily consumption of oral methadone was 53 mg. There were dosage differences between treatment regimes. During the course of treatment the mean dosage for injectable heroin per day decreased significantly and, depending on the treatment regime, almost linearly.. The significance of heroin dosages in heroin-assisted therapy for treatment outcome should be further explored, especially in the light of the markedly higher dosages in Switzerland compared to the UK. During the treatment period, dosages did not increase but generally decreased, indicating no further increase in tolerance.

Topics: Administration, Oral; Adult; Ambulatory Care; Clinical Trials as Topic; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Prescriptions; Drug Utilization; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Methadone; Morphine; Narcotics; Outcome and Process Assessment, Health Care; Substance Abuse Detection; Substance Abuse, Intravenous; Switzerland

To determine the lifetime and recent histories of attempted suicide among entrants to treatment for heroin dependence in three treatment modalities and a non-treatment comparison group; and to ascertain factors associated with a recent history of attempted suicide.. Cross-sectional structured interview.. Sydney, Australia.. Six hundred and fifteen current heroin users: 201 entering methadone/buprenorphine maintenance (MT), 201 entering detoxification (DTX), 133 entering drug free residential rehabilitation (RR) and 80 not in treatment (NT).. A lifetime history of attempted suicide was reported by 34% of subjects, 13% had attempted suicide in the preceding year and 5% had done so in the preceding month. Females were more likely to have lifetime (44% versus 28%) and 12 month (21% versus 9%) suicide attempt histories. The 12 month prevalence of attempted suicide among treatment groups ranged between 11% (MT, NT) and 17% (RR). Factors associated with recent suicide attempts were: being an RR entrant, female gender, younger age, less education, more extensive polydrug use, benzodiazepine use, recent heroin overdose, Major Depression, current suicidal ideation, Borderline Personality Disorder (BPD)and Post-Traumatic Stress Disorder.. Recent suicidal behaviour is a major clinical problem for heroin users, and for females and RR entrants in particular. An essential adjunct to treatment for heroin dependence is routine screening for depression and suicidal ideation, with the provision of appropriate treatment where needed.

Topics: Adolescent; Adult; Age Factors; Ambulatory Care; Antisocial Personality Disorder; Borderline Personality Disorder; Buprenorphine; Cross-Sectional Studies; Depressive Disorder, Major; Drug Overdose; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Mass Screening; Methadone; Middle Aged; Narcotics; Needle-Exchange Programs; New South Wales; Outcome and Process Assessment, Health Care; Patient Admission; Rehabilitation Centers; Risk Factors; Sex Factors; Stress Disorders, Post-Traumatic; Substance Abuse, Intravenous; Suicide, Attempted

The leading cause of death among heroin users is drug overdose. The present study examined the relationship between history of self-reported drug overdoses and social network characteristics among cocaine and opiate users. Data were from cross-sectional surveys administered from March 2001 through February 2003 as part of follow-up of an experimental network oriented HIV prevention intervention. A total of 838 participants with histories of cocaine and opiate use completed the survey. Several social network variables were found to be significantly associated with drug overdose in the prior 2 years, including larger number of network members who were injection drug users and a larger number of conflictual ties among the network members. Even after controlling for age, gender, frequency of injection drug and alcohol use, and health status, network variables continued to have a strong association with history of recent overdose. These data suggest that large drug networks should be targeted for drug overdose prevention interventions.

Topics: Adult; Alcohol Drinking; Baltimore; Cocaine-Related Disorders; Comorbidity; Conflict, Psychological; Crack Cocaine; Drug Overdose; Female; Health Education; Health Knowledge, Attitudes, Practice; Health Status Indicators; Heroin; Heroin Dependence; HIV Infections; Humans; Male; Multivariate Analysis; Risk Factors; Social Facilitation; Social Support; Substance Abuse, Intravenous; Urban Population

Topics: Analgesics, Opioid; Drug Resistance; Drug Therapy, Combination; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Randomized Controlled Trials as Topic

Topics: Double-Blind Method; Drug Resistance; Heroin; Heroin Dependence; Humans; Narcotics; Randomized Controlled Trials as Topic

Topics: Community Mental Health Services; Drug Resistance; Drug Therapy, Combination; Heroin; Heroin Dependence; Humans; Narcotics; Treatment Failure

Topics: Analgesics, Opioid; Drug Resistance; Drug Therapy, Combination; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Randomized Controlled Trials as Topic

Topics: Analgesics, Opioid; Drug Resistance; Drug Therapy, Combination; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Randomized Controlled Trials as Topic; Treatment Failure

We investigated immune, endocrine, and somatic alterations using two animal models of human heroin administration. In a heroin self-administration paradigm, we observed changes in immune function which suggest that the cycle of intermittent drug use is actually a stressor, which in turn not only exacerbates craving and drug-seeking behavior but also collaterally causes suppression of immune function and therefore susceptibility to disease. In another model of rats made physically dependent to heroin, we show that immune function is more broadly compromised, leading to evidence of infection, followed by chronic activation of innate immune function, cachexia, and weight loss.

Topics: Animals; Behavior, Animal; Body Weight; Disease Models, Animal; Drug Administration Routes; Drug Administration Schedule; Heroin; Heroin Dependence; Immune System; Neurosecretory Systems; Rats; Self Administration

Topics: Attitude to Health; Australia; Heroin; Heroin Dependence; Humans; Social Conditions

We seek to establish whether a substantial decline in the supply of heroin, as measured by indicators such as drug purity, is related to changes in drug-related health indicators such as ambulance callouts to heroin overdoses and numbers participating in methadone treatment programmes, and to changes in levels of property crime. The guiding hypothesis is that reduced supply will result in positive health and social outcomes.. Standard time-series methods are employed to analyse official data from local law-enforcement and heroin supply indicators and several health and social outcome indicators within the Australian Capital Territory (ACT), spanning the late 1990s to early 2002. Autoregressive moving average (ARMA) models are estimated to remove autocorrelation from these series. Cross-correlation and autoregression models are then employed to identify the best predictive models.. When autocorrelation has been removed, a reduction in heroin purity predicts a large decline in heroin-related ambulance callouts and an increase in methadone treatment programme enrolments. There is little evidence of an increase in negative outcomes due to heroin users switching to other drugs. A reduction in purity also predicts declines in robbery and burglary but not in theft.. The overall evidence indicates modest links between the declines in heroin supply and increases in positive health outcomes and decreases in crime, as predicted by a simple economic model. Due to the shortness of some of the series and consequent limitations in statistical power, these conclusions should be regarded as tentative.

Topics: Australian Capital Territory; Crime; Drug and Narcotic Control; Health Status; Heroin; Heroin Dependence; Humans; Substance-Related Disorders

To identify prescription drug-seeking behaviour patterns among young people who subsequently died of heroin-related overdose.. Linkage of Medicare and Pharmaceutical Benefits Scheme and Coroner's Court records from Victoria.. Two hundred and two 15-24-year-olds who died of heroin-related overdose between 6 January 1994 and 6 October 1999.. Patterns of use of medical services and prescription drugs listed on the Pharmaceutical Benefits Scheme in the years before death, and use of all drugs just before death.. Polydrug use was reported in 90% of toxicology reports, and prescription drugs were present in 80% of subjects. Subjects accessed medical services six times more frequently than the general population aged 14-24 years, and more than half of all prescribed drugs were those prone to misuse, such as benzodiazepines and opioid analgesics. A pattern of increasing drug-seeking behaviour in the years before death was identified, with doctor-visitation rates, number of different doctors seen and rates of prescriptions peaking in the year before death.. An apparent increase in "doctor shopping" in the years before heroin-related death may reflect the increasing misuse of prescription drugs, but also an increasing need for help. Identification of a pattern of escalating doctor shopping could be an opportunity for intervention, and potentially, reduction in mortality.

Topics: Adolescent; Adult; Clinical Pharmacy Information Systems; Drug Overdose; Drug Prescriptions; Family Practice; Female; Health Services Misuse; Heroin; Heroin Dependence; Hotlines; Humans; Male; Patient Acceptance of Health Care; Retrospective Studies; Victoria

Topics: Drug Prescriptions; England; Heroin; Heroin Dependence; Humans; Malpractice; Narcotics

One concern about the widespread use of cannabis is that exposure to its active ingredient, delta-9-tetrahydrocannabinol (THC), might increase future reinforcing effects of other abused drugs such as heroin. In this study, we investigated the effects of pre-exposure to THC on subsequent intravenous self-administration of heroin by Sprague-Dawley rats. In one group of rats, we studied (1) acquisition of heroin self-administration behavior using a continuous-reinforcement (fixed-ratio (FR) 1) schedule, (2) heroin dose-response relationships using an FR1/variable-dose schedule, and (3) reinforcing efficacy of heroin using a progressive-ratio schedule. The number of rats pre-exposed to THC that subsequently learned to self-administer 50 microg/kg injections of heroin within 10 daily sessions did not differ from vehicle-pretreated controls. In contrast, rats pre-exposed to THC subsequently self-administered significantly more heroin injections per session and showed significantly shorter post-injection pauses over a range of heroin doses (12.5-100 microg/kg/injection) using the variable-dose schedule. Interestingly, the maximum effort rats would exert to receive an injection of the different doses of heroin under the progressive-ratio schedule was not altered by THC pre-exposure. In a second group of rats, we varied the 'price' of heroin (responses required/dose), by manipulating FR response requirements at different doses of heroin across sessions, to calculate demand and response output curves. Again, consumption was significantly higher in the THC-treated rats at the lowest prices of heroin (FR1/100 microg/kg and FR1/50 microg/kg) but there were no differences in the reinforcing efficacy of heroin between THC- and vehicle-pretreated rats. Altogether, these results demonstrate that pre-exposure to THC alters some pharmacological effects of heroin that determine frequency of heroin taking, but offer no support for the hypothesis that pre-exposure to THC alters heroin's efficacy as a reinforcer.

Topics: Analgesics, Non-Narcotic; Analysis of Variance; Animals; Behavior, Animal; Conditioning, Operant; Dose-Response Relationship, Drug; Dronabinol; Drug Administration Schedule; Drug Interactions; Heroin; Heroin Dependence; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Reinforcement, Psychology; Self Administration

Prompted by the history of heroin diffusion in the United States, press reports and building on previous research into retail heroin distribution, ethnographic research was undertaken identifying and describing retail distribution and diffusion of heroin in and into medium- and small-sized towns in the mid-Hudson region of New York State.. In conjunction with fieldwork, in-depth tape-recorded interviews were conducted with recent admissions (30 days) at 28 different drug treatment facilities located in the region. Interviews were also conducted with drug counselors, narcotic officers, drug treatment administrators and the county commissioners of mental hygiene.. Heroin-dependent individuals who have access to cheaper heroin in urban areas, such as New York City, Newark, and Patterson, New Jersey, drive retail heroin distribution in the mid-Hudson region. They travel to these cities, purchase heroin in quantity (costing $8-10 per bag), return to the region and sell premium-priced heroin ($20-$25 per bag) mostly to irregular users who do not have access to retail drug sellers in urban areas.. Price disparity contributes to a recurrent process whereby irregular users who are able to gain access to cheaper heroin in urban areas, return to the mid-Hudson and sell premium-priced heroin to other users who do not have access to cheaper heroin. This process contributes to the diffusion of heroin abuse.

Topics: Adolescent; Adult; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Middle Aged; New York; New York City; Prevalence; Substance Abuse, Intravenous

An evaluation of time perception in drug addicts was carried out in 12 s intervals, using 10 attempts with up to 0.1 s precision. Eighty-two heroin addicts in abstinent and post abstinent periods have been observed, the results being compared to 52 healthy controls. During the first two days after admission to the hospital (abstinent syndrome development), time intervals values were lower in patients than in controls, reaching a precision of recalling 12s, with a following exceeding of this index. On day 15-16, time perception returned to precise level (post abstinent period). Depending on drug addiction duration and individual features of brain hemisphere asymmetry, changes in subjective time perception were revealed in the study.

Topics: Adolescent; Adult; Brain; Functional Laterality; Heroin; Heroin Dependence; Hospitalization; Humans; Length of Stay; Male; Severity of Illness Index; Substance Withdrawal Syndrome; Time Factors

This study examined heroin initiation and route of administration among 16 female adolescents in the greater Baltimore Metropolitan area. Participants were more than twice as likely to be introduced to heroin by a male friend or boyfriend (IHM) than introduced to heroin by other means (IHO). The majority of IHM females were introduced by a male friend rather than a romantic partner. No relationship was found between path of initiation (IHM, IHO) and initial route of administration (inhalation, smoking, injecting) or history of injection (ever injected, never injected). The effect of opposite-gender peer influence in the initiation of female adolescent heroin use is discussed along with how the current findings may influence treatment and prevention efforts. A statistically significant relationship was found for initial route of administration and for history of injection. Ninety-four percent of participants reported initiation of heroin use by inhalation, while an alarming 75% of participants reported injecting heroin at some time during their history of use. Participants were no more likely to be introduced to injection by a boyfriend or male friend than by other means. The finding that the majority of females first try heroin through inhalation is consistent with an increased use of heroin by this method among young people in recent years. However, the majority of users in this study used heroin through injection at least once in their addict career, a route of administration associated with increased health and safety risks. Potential explanations for the progression from snorting to injection are presented as well as implications for the delivery of prevention and treatment services.

Topics: Administration, Inhalation; Adolescent; Adolescent Behavior; Adult; Age Factors; Baltimore; Female; Friends; Heroin; Heroin Dependence; Humans; Interpersonal Relations; Male; Peer Group; Persuasive Communication; Sex Factors; Social Support; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Surveys and Questionnaires

Environmental stimuli and conditioned cues associated with heroin can induce drug-seeking behavior, but how heroin lapse interacts with cues is unclear. Rats were trained to nose-poke for i.v. heroin for 14 days and then tested for heroin seeking after withdrawal from heroin self-administration. Heroin seeking induced by cues persisted over several weeks after withdrawal, and the responding was not easily extinguished after 4 weeks withdrawal. A single injection of heroin (250 micro g/kg) enhanced the responding at early stage of withdrawal, but a low dose of heroin (50, 250 micro g/kg) suppressed the responding induced by contextual or conditioned cues at 4 weeks of withdrawal. The results suggest that prolonged withdrawal may increase the risk of relapse to heroin seeking.

Topics: Animals; Conditioning, Operant; Cues; Disease Models, Animal; Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Male; Rats; Rats, Sprague-Dawley; Recurrence; Reward; Risk Factors; Self Administration; Substance Withdrawal Syndrome; Time Factors

Prenatal heroin exposure disrupts hippocampal cholinergic synaptic function and related behaviors. Biochemical studies indicate an increase in the number of presynaptic high-affinity choline transporter (HACT) sites, as assessed by [3H]hemicholinium-3 (HC-3) binding. The present study was designed to assess whether this effect involves global upregulation of the transporter, or whether disruption occurs with a specific tempero-spatial distribution. Pregnant mice were given 10mg/kg per day of heroin subcutaneously on gestational days (GD) 9-18. Autoradiographic distribution of HC-3 binding sites was evaluated in the hippocampus of the offspring at postnatal days 15, 25, and 53. These results, suggestive of hippocampal "miswiring," are likely to explain the net impairment of cholinergic synaptic function after prenatal heroin exposure, despite the simultaneous upregulation of both presynaptic cholinergic activity and postsynaptic receptors. Understanding the subregional selectivity of hippocampal defects can lead to the development of strategies that may potentially enable therapeutic interventions to offset or reverse the neurobehavioral defects.

Topics: Acetylcholine; Animals; Binding, Competitive; Female; Hemicholinium 3; Heroin; Heroin Dependence; Hippocampus; Male; Membrane Transport Proteins; Mice; Neural Pathways; Pregnancy; Prenatal Exposure Delayed Effects; Presynaptic Terminals; Radioligand Assay; Synaptic Membranes; Synaptic Transmission

Na, K, Ca, Mg, P, Fe, Cu, Zn and Se concentrations were determined in the serum of 106 heroin addicts and were compared with the concentrations obtained in a control group formed of 186 apparently healthy individuals. Heroin addicts displayed K and Se mean concentrations lower (p < 0.05), and Na, Mg, P mean concentrations and a Cu/Zn ratio higher (p < 0.05) than those mean values observed in the control group. The Mg and P concentrations in the serum of heroin addicts tended to normalize when age increased. The heroin addicts included in the methadone maintenance treatment program had higher serum mean concentrations of K and Mg than the heroin addicts in the detoxification process. The Na, K and Mg concentrations displayed highly significant correlations, with a different behavior for the heroin addicts group and the control group. When applying factor analysis and representing the scores of the first and second factors, the heroin addicts tended to differentiation from the control group. However, methadone substitution treatment was not able to normalize these concentrations.

Topics: Adult; Atlantic Islands; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Statistics as Topic; Trace Elements

Topics: Administration, Intranasal; Adolescent; Adult; Female; Heroin; Heroin Dependence; Humans; Life Style; Male; Pilot Projects; Risk-Taking; Sexual Behavior; Substance-Related Disorders; Surveys and Questionnaires

Thirty male Sprague-Dawley rats were divided into two groups and trained to self-administer either saline (n = 14) or heroin (0.1 mg/kg per injection, n = 16) for 10-12 days until a stable self-administration (SA) behavior was achieved. After 8-9 days of withdrawal, each group was divided into two subgroups for reinstatement tests and functional magnetic resonance image (fMRI) scanning, respectively, to determine the neural correlates of the reinstatement of heroin-seeking behavior. For reinstatement testing, heroin-SA rats (n = 10) displayed robust reinstatement of drug-seeking behavior triggered by an acute heroin priming injection, whereas saline control rats (n = 8) did not show such a behavioral response. Regional positive or negative blood oxygen level-dependent (BOLD) signals, induced by heroin priming injection, were observed in both groups of rats during fMRI scanning. However, such heroin-induced positive BOLD signal primarily in the prefrontal cortex and parietal cortex was significantly attenuated in heroin-SA rats (n = 6) when compared to saline control rats (n = 6). Similarly, the heroin-induced negative BOLD signal in the subcortical regions, such as in the nucleus accumbens and hippocampus, was also significantly attenuated in both signal intensity and number of brain voxels activated in heroin-SA rats. These data demonstrate that heroin-induced reinstatement of drug-seeking behavior coincides with a significant, enduring reduction in opiate-induced brain activity in heroin-SA rats, suggesting a possible role of opiate tolerance in mediating reinstatement of drug-seeking behavior.

Topics: Animals; Behavior, Animal; Brain; Cerebrovascular Circulation; Drug Tolerance; Heroin; Heroin Dependence; Hippocampus; Injections, Intravenous; Magnetic Resonance Imaging; Male; Nucleus Accumbens; Oxygen; Parietal Lobe; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Recurrence; Self Administration

Functional MRI (fMRI) was employed to determine whether repeated heroin self-administration (SA) produces tolerance or sensitization in the brain of heroin-SA rats. Twelve rats were evenly divided into saline and heroin (0.06 mg/kg, 4 hr/day) SA groups. There was a progressive increase in drug-SA behavior and daily heroin intake during the 8-9 days of heroin-SA training. Within 24 hr after the last session of daily SA, acute heroin (0.1 mg/kg) administration induced regional blood oxygen level-dependent (BOLD) signals in both groups of rats. The positive BOLD signals appeared mainly in the cortical regions, including the prefrontal cortex, cingulate, and olfactory cortex, while the negative BOLD signals were predominantly located in subcortical regions such as caudate and putamen, nucleus accumbens, thalamus, and hypothalamus. However, the number of activated voxels or BOLD-signal intensity was significantly less in heroin-SA rat in regions of prefrontal cortex, nucleus accumbens, and thalamus, etc., compared to the changes in the saline control rats. Application of gamma-vinyl GABA (100 mg/kg), an irreversible GABA-transaminase inhibitor, failed to block opiate actions in the heroin-SA rats. Together, these data suggest that repeated heroin-SA produces tolerance or desensitization of opiate actions in the rat brain, which may in turn potentiate drug SA behavior and drug intake.

Topics: Animals; Brain; Drug Tolerance; gamma-Aminobutyric Acid; Heroin; Heroin Dependence; Magnetic Resonance Imaging; Male; Rats; Rats, Sprague-Dawley; Self Administration

This study investigates the type and extent of changes in route of drug administration among heroin users after treatment: whether injectors move to other routes of use; whether changes in route for one drug influence routes used for other drugs; and associations between changes in route of administration and other substance use outcomes. The sample comprised 641 heroin users recruited to 54 UK treatment programmes. At intake, the main routes of heroin use were injecting (61%) and "chasing the dragon" (37%). After 1 year, 81% of those using heroin took it by the same route as at intake, while 19% reported a change, with 14% switching from injecting to chasing. Changes from injecting to chasing were associated with improvements in other substance use behaviours. Changes in route represent an important aspect of drug-taking behaviours. Interventions to prevent the change to injecting should be developed and offered to noninjectors. "Reverse transitions" (from injecting to chasing) may represent a useful intermediate treatment goal for drug injectors who cannot achieve abstinence.

Topics: Administration, Inhalation; Adult; Amphetamines; Cocaine; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Narcotics; Risk-Taking; Substance Abuse, Intravenous; Treatment Outcome

This article discusses the predicament of historians becoming part of the history they are investigating and illustrates the issue in a particular case. The case is that of the randomized controlled trial (RCT)-more specifically, its use for testing the effects of providing heroin to severe heroin abusers. I counter the established view of the RCT as a matter of timeless logic and argue that this research design was developed in the context of administrative knowledge making under twentieth-century economic liberalism of which it epitomizes some central values. I also argue that the applicability of the RCT depends on the degree to which its advocates can define the issue to be studied according to its inherent values. Next, I demonstrate how advocates of an RCT with heroin provision in the Netherlands steered the political discussion on heroin provision and how the values of economic liberalism also shaped the results of the Dutch maintenance experiment. In addition, I relate how my analysis of this experiment became part of political debates in the Netherlands. Contrary to my intentions, adversaries of heroin maintenance used my critique on the heroin RCT as an argument against heroin maintenance. Such risks are inherent to historiography and sociology of science aiming at practical relevance while challenging treasured scientific beliefs. I conclude that it still seems better to expose arguments on unjustified certainties than to suppress them for strategic reasons.

Topics: Heroin; Heroin Dependence; Historiography; Humans; Netherlands; Randomized Controlled Trials as Topic; Severity of Illness Index

Topics: Drug Overdose; Emergency Service, Hospital; Heroin; Heroin Dependence; Humans; Narcotics; Pulmonary Edema

Topics: Australia; Drug Overdose; Heroin; Heroin Dependence; Humans

Topics: Adolescent; Adult; Heroin; Heroin Dependence; Humans; Narcotics; Needle-Exchange Programs; New South Wales; Substance Abuse, Intravenous; Substance-Related Disorders

To determine whether changes in orthoptic status take place during withdrawal from heroin and/or methadone.. A prospective study of patients, using a repeated measures design, attending a 5 day naltrexone compressed opiate detoxification programme.. 83 patients were seen before detoxification (mean age 27.1 (SD 4.6) years) and 69 after detoxification. The horizontal angle of deviation became less exo/more eso at distance (p<0.001) but no significant change was found at near (p = 0.069). Stereoacuity, visual acuity, and convergence were found to be reduced in the immediate post-detoxification period. Prism fusion range, refractive error, subjective accommodation, and objective accommodation at 33 cm did not reduce but a small decrease was found in objective accommodation at 20 cm.. The eso trend found in these patients may be responsible for the development of acute concomitant esotropia in some patients undergoing heroin detoxification. However, the mechanism for this trend does not appear to be caused by divergence insufficiency or sixth nerve palsy.

Topics: Accommodation, Ocular; Adolescent; Adult; Convergence, Ocular; Diplopia; Eye Movements; Heroin; Heroin Dependence; Humans; Methadone; Naltrexone; Narcotics; Refractive Errors; Vision, Binocular; Visual Acuity

A sample of 535 entrants to opioid dependence treatments across three treatment modalities were administered a structured interview to ascertain the prevalence of non-injecting heroin use. Ten per cent of participants had used heroin primarily by smoking/inhaling in the month preceding interview, and 9% had used heroin and other drugs exclusively by non-injecting routes. Non-injectors were younger (25.3 vs. 29.5 years), had higher levels of education (10.6 vs. 10.0 years), were more likely to be employed (33 vs. 18%) and had lower levels of recent crime (31 vs. 56%). They also had shorter heroin using careers (5.1 vs. 9.9 years), fewer symptoms of dependence (5.1 vs. 5.6), had been enrolled in fewer previous treatment episodes (3.3 vs. 11.5) and had less extensive lifetime (8.0 vs. 9.1 drug classes) and recent (3.6 vs. 4.9) polydrug use. Non-injectors were substantially less likely to report lifetime (13% vs. 58%) or recent (2% vs. 29%) heroin overdoses. There were no differences between the general physical and psychological health of the two groups. While non-injectors had a lower level of post-traumatic stress disorder (29% vs. 34%), there were no differences in levels of major depression, attempted suicide, antisocial personality disorder, or borderline personality disorder. A substantial minority of Australian treatment entrants are now using heroin exclusively by non-injecting routes. While this group is younger, and has substantially reduced risk of overdose and blood borne virus transmission, the physical and psychological health of non-injectors mirrors that of injectors.

Topics: Administration, Inhalation; Adolescent; Adult; Antisocial Personality Disorder; Borderline Personality Disorder; Buprenorphine; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Overdose; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Methadone; Middle Aged; Narcotic Antagonists; Residential Treatment; Suicide, Attempted

A patient who inhaled heroin vapour (chasing the dragon), resulting in temporary parkinsonism, is described. A reversible deficiency of tetrahydrobiopterin, causing altered dopamine metabolism, is demonstrated as the metabolic basis of this aspect of the encephalopathy.

Topics: Adult; Biopterins; Brain; Brain Diseases, Metabolic; Electroencephalography; Epilepsy; Female; Heroin; Heroin Dependence; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Magnetic Resonance Imaging; Parkinsonian Disorders

A fully validated procedure for the simultaneous determination of morphine (MOR), morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), 6-acetylmorphine (6AM), codeine (COD), codeine-6-glucuronide (C6G), acetylcodeine (AC), noscapine (NOS) and papaverine (PAP) based on liquid chromatography followed by electrospray mass spectrometry applying multiple reaction monitoring (LC-ESI-MS/MS) in urine samples is described. The extraction was carried out on a Zymark Rapid Trace Workstation using C18 solid-phase extraction cartridges. The separation was performed in 19 min on an Agilent 1100 HPLC system, using a Phenomenex C18 AQUA column (4 microm, 150 mm x 2 mm), which is coupled with an Applied Biosystems API 2000 mass spectrometer. Deuterated analogues were used as internal standards. The limits of detection were in the range of 0.1 ng/ml (PAP) to 7.4 ng/ml (M6G), the coefficients of correlation were higher than 0.996, the precisions ranged from 3% to 12% and the absolute recoveries were between 45% (M3G) and 98% (MOR). Analyses of samples from patients of a heroin prescription program demonstrated the usefulness of the procedure for the analytical differentiation between prescribed synthetic heroin (diamorphine) use and non-prescription heroin abuse on the basis of urine analysis. After the ingestion of pharmaceutical heroin only general markers for heroin use were detected, which are MOR, M3G, M6G and 6AM, respectively. When illicit heroin was abused, additionally to further general markers (COD, C6G) specific markers for non-prescription heroin abuse (AC, NOS, PAP) were found. However, it must be kept in mind that only AC may be regarded as absolute specific marker of non-prescription heroin, because all other compounds may appear in urine after ingestion of opiate alkaloids containing medicines or foods (e.g. poppy seeds). Therefore, patients of a heroin prescription program should be advised not to ingest such products.

Topics: Calibration; Chromatography, High Pressure Liquid; Heroin; Heroin Dependence; Humans; Illicit Drugs; Mass Spectrometry; Reference Standards; Reproducibility of Results; Sensitivity and Specificity

To identify patterns of mental health, prescription drug use and personal circumstances associated with heroin overdose in young people.. Linkage of data on use of Pharmaceutical Benefits Scheme (PBS) prescription drugs with data from a self-report questionnaire.. Inner metropolitan Melbourne, Australia.. 163 young people, 15-30 years, using heroin.. Personal circumstances, mental health (as measured by various scales), and PBS-listed prescription drug use.. Young people using heroin reported high rates of feelings of hopelessness, depression, antisocial behaviour, self-harm and diagnosed mental illness. A prior history of overdose was associated with previous mental illness, which in turn was associated with being female, having poor social support, being dissatisfied with relationships, and living alone or in temporary accommodation. While feelings of hopelessness and antisocial behaviour were strongly associated with overdose history, the number of PBS prescription drugs used had a very strong relationship with overdose, particularly benzodiazepines, other opioids, tricyclic antidepressants and tranquillisers.. Further research to explore causal relationships between prescription drugs and heroin overdose is warranted. Improved data linkage to PBS records for general practitioners may facilitate safer prescribing practices.

Topics: Adolescent; Adult; Age Distribution; Drug Overdose; Drug Prescriptions; Female; Heroin; Heroin Dependence; Humans; Life Style; Logistic Models; Male; Mental Disorders; Probability; Registries; Risk Assessment; Sex Distribution; Socioeconomic Factors; Surveys and Questionnaires; Survival Rate; Urban Population; Victoria