heroin and Opioid-Related-Disorders

Injectable opioid agonist treatment (iOAT) is effective for opioid use disorder (OUD), yet little is known about client preferences for accessing iOAT (e.g., with diacetylmorphine, hydromorphone, buprenorphine, fentanyl, etc.). Best-worst scaling (BWS) is a preference elicitation method from health economics that has never been applied to addiction care broadly, or iOAT specifically. We describe the stages of developing a BWS scale that assesses iOAT clients' treatment delivery preferences to inform program planning and maximize healthcare efficiency.. We underwent several steps to reveal the relevant attributes/levels and design the scale structure. An initial list of potential attributes and levels was established from a literature review and prior qualitative data. Then, we conducted semi-structured interviews and focus groups with clients (n=21) on their iOAT preferences to confirm the attributes and prioritize/include new ones. Next, we conducted semi-structured interviews and focus groups with iOAT experts and stakeholders to receive their input on the draft list of attributes and levels. A BWS profile case design was piloted with iOAT clients (n=18) from different sites during a think aloud interview. After several rounds of revisions, the final version was tested by iOAT clients (n=2) before the scale was launched.. We developed a person-centered scale that assesses current and former iOAT clients' most and least wanted aspects of iOAT delivery. The final version yielded 7 unique attributes: choice of medication, choice of dose, convenience, location & space, scheduling & routines, staff & training, and types of services offered.. This scale can help expand iOAT programs in a way that is person-centered, rapid, and affordable. The methodology is a guide for other regions with similar populations who aim to develop strong quantitative methodologies that prioritize client collaboration.

Topics: Analgesics, Opioid; Health Services; Heroin; Humans; Hydromorphone; Opioid-Related Disorders

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

Opioid use disorder (OUD) is a major current cause of morbidity and mortality. Long-term exposure to short-acting opioids (MOP-r agonists such as heroin or fentanyl) results in complex pathophysiological changes to neuroimmune and neuroinflammatory functions, affected in part by peripheral mechanisms (e.g., cytokines in blood), and by neuroendocrine systems such as the hypothalamic-pituitary-adrenal (HPA) stress axis. There are important findings from preclinical models, but their role in the trajectory and outcomes of OUD in humans is not well understood. The goal of this narrative review is to examine available data on immune and inflammatory functions in persons with OUD, and to identify major areas for future research. Peripheral blood biomarker studies revealed a pro-inflammatory state in persons with OUD in withdrawal or early abstinence, consistent with available postmortem brain studies (which show glial activation) and diffusion tensor imaging studies (indicating white matter disruptions), with gradual abstinence-associated recovery. The mechanistic roles of these neuroimmune and neuroinflammatory changes in the trajectory of OUD (including recovery and medication management) cannot be examined practically with postmortem data. Collection of longitudinal data in larger-scale human cohorts would allow examination of these mechanisms associated with OUD stage and progression. Given the heterogeneity in presentation of OUD, a precision medicine approach integrating multi-omic peripheral biomarkers and comprehensive phenotyping, including neuroimaging, can be beneficial in risk stratification, and individually optimized selection of interventions for individuals who will benefit, and assessments under refractory therapy.

Topics: Analgesics, Opioid; Diffusion Tensor Imaging; Heroin; Humans; Neuroimmunomodulation; Opioid-Related Disorders

Take home naloxone (THN) programs have been rapidly upscaled in response to increasing opioid-related mortality. One often cited concern is that naloxone provision could be associated with increased opioid use, due to the availability of naloxone to reverse opioid overdose. We conducted a systematic review to determine whether THN provision is associated with changes in substance use by participants enrolled in THN programs.. We conducted a systematic review of the literature to assess changes in heroin or other substance use by people who use opioids following THN provision.. Seven studies with 2578 participants were included. Of the seven studies, there were two quasi-experimental studies and five cohort studies. Based on the Joanna Briggs Institute quality assessment, four studies were of moderate quality and three studies were of high quality. Of the five studies that reported on the primary outcome of heroin use, no study found evidence of increased heroin use across the study population. Five studies reported on other substance use (benzodiazepines, alcohol, cocaine, amphetamine, cannabis, prescription opioids), none of which found evidence of an increase in other substance use associated with THN provision. Four studies reported on changes in overdose frequency following THN provision: three studies reporting no change, and one study of people prescribed opioids finding a reduction in opioid-related emergency department attendances for participants who received naloxone.. We found no evidence that THN provision was associated with increased opioid use or overdose. Concerns that THN supply may lead to increased substance use were not supported by data from reviewed studies.

Topics: Analgesics, Opioid; Drug Overdose; Heroin; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Realization of the life-saving potential of "take-home naloxone" has been a personal journey, but it has also been a collective journey. It has been a story of individual exploration and growth, and also a story of changes at a societal level. "Take-home naloxone" has matured since its first conceptualization a quarter of a century ago. It required recognition of the enormous burden of deaths from drug overdose (particularly heroin and other opioids), and also realization of critical clusterings (such as post-release from prison). It also required realization that, since many overdose deaths are witnessed, we can potentially prevent many deaths by mobilizing drug users themselves, their families, and the wider caring community to act as intervention workforce to give life-saving interim emergency care. Summary of Scope: This article explores 5 areas (many illustrations UK-based where the author works): firstly, the need for strong science; secondly, our improved understanding of opioid overdose and deaths; thirdly, the search for greater impact from our policies and interventions; fourthly, developing better forms of naloxone; and fifthly, examining the challenges still to be addressed.. "Take-home naloxone" is an exemplar of harm reduction with potential global impact - drug policy and practice for the public good. However, "having the potential" is not good enough - there needs to be actual implementation. This will be easier once the component parts of "take-home naloxone" are improved (better naloxone products, better training aids, revised legislation, and explicit funding support). Many improvements are already possible, but we hesitate about implementation. It is our responsibility to drive progress faster. With "take-home naloxone," we can be proud of what we have achieved, but we must also be humble about how much more we still need to do.

Topics: Analgesics, Opioid; Drug Overdose; Heroin; Humans; Naloxone; Narcotic Antagonists; Opiate Overdose; Opioid-Related Disorders

Opioid Use Disorder (OUD) is a chronic relapsing disorder that has severe negative impacts on the individual, the family, and the community at large. In 2021, opioids contributed to nearly 70% of all drug overdose deaths in the United States. This number of opioid related deaths coincides with a significant rise in the use of fentanyl, a synthetic opioid that is 150 times more potent than morphine. Furthermore, this overdose trend has spared no demographic and costs the nation an estimated $51.2 billion annually. Thus, it is imperative to better understand the underlying mechanisms of OUD in an effort to identify new treatment targets. Using animal models, studies have shown that rats readily self-administer heroin and increase seeking following exposure to cues for drug, the drug itself, or stress. We have shown that treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, can reduce heroin taking and seeking behavior in rats. Therefore, using our rodent model, we established a fentanyl self-administration paradigm to test whether acute treatment with the GLP-1R agonist also can reduce fentanyl seeking in fentanyl experienced rats. The results showed that rats readily self-administered fentanyl (2.5 ug/kg) intravenously, with marked individual differences in drug taking behavior. As with other drugs of abuse tested, rats exhibited high seeking behavior when challenged with a drug-related cue or, after a period of extinction, the drug itself. Here, acute treatment with the GLP-1R agonist, liraglutide (0.3 mg/kg s.c.), was found to attenuate both cue-induced fentanyl seeking and drug-induced reinstatement of fentanyl seeking with the same efficacy as the currently approved partial opioid agonist, buprenorphine. Taken together, these data suggest that a known satiety signal, GLP-1, may serve as an effective non-opioid alternative for the treatment of OUD.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cues; Fentanyl; Glucagon-Like Peptide-1 Receptor; Heroin; Liraglutide; Opioid-Related Disorders; Rats; Self Administration

There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin.  OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.. We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).. We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment).. We used standard Cochrane methods.. We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-u. There is  very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Opioid-Related Disorders; Pharmaceutical Preparations

Novel buprenorphine dosing strategies have emerged with an aim to transition patients from opioid agonists to buprenorphine without prerequisite opioid withdrawal. We applied a configurational approach to a subset of data from our earlier systematic review to answer the following question: when patients received a buprenorphine initiation strategy aimed to eliminate prerequisite withdrawal, what factors consistently distinguished patients that experienced withdrawal during the initiation process from patients that did not?. From the 24 cases identified by our systematic review, we included cases that were treated using buprenorphine microdosing strategies (oral or transdermal), cases with opioid use disorder, and cases that fully transitioned to buprenorphine without continuing the full opioid agonist. Configurational analysis was used to identify combinations of patient and regimen level factors that uniquely distinguished cases experiencing withdrawal during induction.. Fourteen cases were included in our analysis, of which 9 experienced opioid withdrawal symptoms. Three factors were involved in explaining both the presence and absence of withdrawal symptoms: history of heroin use, history of methadone use, and duration of overlap between buprenorphine and the full opioid agonist during induction. For the presence of withdrawal symptoms, the addition of a fourth factor "buprenorphine starting dose" resulted in a model with perfect consistency and coverage; for the absence of withdrawal symptoms, the addition of a fourth factor "induction duration" similarly resulted in a model with perfect consistency and 80% coverage.. Application of configurational methods allowed synthesis of case reports identified through a systematic review.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Given the ongoing opioid crisis, novel interventions to treat severe opioid use disorder (OUD) are urgently needed. Injectable opioid agonist therapy (iOAT) with diacetylmorphine or hydromorphone is effective for the treatment of severe, treatment-refractory OUD, however barriers to implementation persist. Intravenous buprenorphine for the treatment of OUD (BUP iOAT) has several possible advantages over traditional iOAT, including a safety profile that might enable take-home dosing. We aimed to characterize injecting practices among real-world populations of persons who regularly inject buprenorphine, as well as associated adverse events reported in order to inform a possible future BUP iOAT intervention.. We conducted a systematic review. We searched MEDLINE, EMBASE, and PsycINFO from inception through July 2020 and used backwards citation screening to search for publications reporting on dose, frequency among persons who regularly inject the drug, or adverse events associated with intravenous use of buprenorphine. The review was limited to English language publications and there was no limitation on study type. Study quality and risk of bias was assessed using the Mixed Methods Appraisal Tool. Narrative synthesis was used in reporting the results.. Eighty-eight studies were included in our review. Regular injection of buprenorphine was identified across diverse settings world-wide. Daily dose of oral buprenorphine injected was < 1-12 mg. Frequency of injection was 0-10 times daily. Adverse events could be characterized as known side effects of opioids/buprenorphine or injection-related complications. Most studies were deemed to be of low quality.. Extramedical, intravenous use of buprenorphine, continues to be documented. BUP iOAT may be feasible and results may inform the development of a study to test the efficacy and safety of such an intervention. Future work should also examine acceptability among people with severe OUD in North America. Our review was limited by the quality of included studies.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Hydromorphone; Opiate Substitution Treatment; Opioid-Related Disorders

The incidence of chronic heroin use disorder, including overdose deaths, has reached epidemic proportions. Here we summarise and evaluate our knowledge of the relationship between chronic heroin use disorder and the brain through a narrative review. A broad range of areas was considered including causal mechanisms, cognitive and neurological consequences of chronic heroin use and novel neuroscience-based clinical interventions. Chronic heroin use is associated with limited or very limited evidence of impairments in memory, cognitive impulsivity, non-planning impulsivity, compulsivity and decision-making. Additionally, there is some evidence for certain neurological disorders being caused by chronic heroin use, including toxic leukoencephalopathy and neurodegeneration. However, there is insufficient evidence on whether these impairments and disorders recover after abstinence. Whilst there is a high prevalence of comorbid psychiatric disorders, there is no clear evidence that chronic heroin use per se causes depression, bipolar disorder, PTSD and/or psychosis. Despite the growing burden on society from heroin use, knowledge of the long-term effects of chronic heroin use disorder on the brain remains limited. Nevertheless, there is evidence for progress in neuroscience-based interventions being made in two areas: assessment (cognitive assessment and neuroimaging) and interventions (cognitive training/remediation and neuromodulation). Longitudinal studies are needed to unravel addiction and neurotoxic mechanisms and clarify the role of pre-existing psychiatric symptoms and cognitive impairments.

Topics: Bipolar Disorder; Brain; Cognitive Dysfunction; Comorbidity; Heroin; Humans; Impulsive Behavior; Neuroimaging; Neurosciences; Opioid-Related Disorders; Psychotic Disorders

Topics: Alcoholism; Body Mass Index; Bone Diseases, Metabolic; Buprenorphine; Female; Heroin; Humans; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; Sex Factors; Testosterone

Illegally manufactured potent synthetic opioids (IMPSO) like fentanyl have contributed to rises in overdose deaths in parts of North America and Europe. While many of these substances are produced in Asia, there is little evidence they have entered markets there. We consider the susceptibility to IMPSO's encroachment in markets in the Asia-Pacific region.. Our analysis focuses on Australia, China, India, and Myanmar. Using a mixed-methods approach comprising interviews, literature review, and secondary data analyses, we examine factors facilitating or impeding incursion of IMPSO. Finally, we illustrate the potential for IMPSO fatalities in Australia.. Australia reports some signs of three facilitating factors to IMPSO's emergence: 1) existing illicit opioid markets, 2) disruption of opioid supply, and 3) user preferences. The other three countries report only existing illicit opioid markets. While diverted pharmaceutical opioids are a noted problem in Australia and India, heroin is the dominant opioid in all four countries. There are divergent trends in heroin use, with use declining in China, increasing in India, and stable in Australia and Myanmar. If IMPSO diffused in Australia as in North America from 2014 to 2018, and our assumptions generally hold, deaths from IMPSO could range from 1500-5700 over a five-year period.. This analysis and illustrative calculations serve as an early indication for policymakers. With the exception of Australia, many countries in the region fail to properly record overdose deaths or monitor changes in local drug markets. Early assessment and monitoring can give officials a better understanding of these changing threats.

Topics: Asia; Australia; China; Drug Overdose; Fentanyl; Heroin; Humans; India; Myanmar; Opioid-Related Disorders; Synthetic Drugs

Topics: Drug Overdose; Fentanyl; Heroin; Humans; Nursing Diagnosis; Opioid-Related Disorders; United States

South Africa has seen a sharp increase in treatment admission trends for opioids despite beliefs that rates of opioid use remain low and do not represent a major problem. To advocate for the extension of Opioid Use Disorder (OUD) treatment and harm minimisation services in South Africa, better estimates of the extent of opioid use is needed. This paper responds to this need by describing (i) trends in treatment utilization for opioid-related problems in South Africa and (ii) differences in the profile of patients accessing treatment for different classes of opioids - heroin, 'nyaope' and codeine use.. Data were collected from 83 specialist treatment centres participating in the South African Community Epidemiology Network on Drug Use between 2012 and 2017. Descriptive analyses were conducted to describe the sociodemographic profile of patients and multiple logistic regression was used to explore socio-demographic and clinical factors associated with admission to treatment for opioid use disorders (OUD) .. From January 2012 to December 2017, data from 11 2032 treatment episodes were collated. Of these, 20 319 (18.1%) were from patients admitted for an OUD. Over time, the proportion of overall opioid-related admissions increased significantly from 16.1% of all admissions in 2012 to 20.0% in 2017 (p <0.001). Data also suggests a significant increase in the overall proportion of patients reporting injection drug use, from 1.6% in 2013 to 3.5% in 2017 (p <0.001). Clear differences in employment status, referral sources between classes of opioids were also noted.. Over the last 5 years, South Africa has seen an increase in the proportion of opioid related disorders (OUD) treatment admissions. Public health interventions, evidence-based harm reduction approaches and improving access to treatment are among the interventions urgently needed to reduce the harms associated with the increased use of opioids in South Africa.

Topics: Analgesics, Opioid; Codeine; Heroin; Humans; Opioid Epidemic; Opioid-Related Disorders; Pharmaceutical Preparations; South Africa

Fentanyl is a powerful opioid anesthetic and analgesic, the use of which has caused an increasing public health threat in the United States and elsewhere. Fentanyl was initially approved and used for the treatment of moderate to severe pain, especially cancer pain. However, recent years have seen a growing concern that fentanyl and its analogs are widely synthesized in laboratories and adulterated with illicit supplies of heroin, cocaine, methamphetamine, and counterfeit pills, contributing to the exponential growth in the number of drug-related overdose deaths. This review summarizes the recent epidemic and evolution of illicit fentanyl use, its pharmacological mechanisms and side effects, and the potential clinical management and prevention of fentanyl-related overdoses. Because social, economic, and health problems that are related to the use of fentanyl and its analogs are growing, there is an urgent need to implement large-scale safe and effective harm reduction strategies to prevent fentanyl-related overdoses.

Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Illicit Drugs; Opioid-Related Disorders; Public Health

Opium poppy has important medical, socioeconomic, forensic and political implications. More than 80 benzylisoquinoline alkaloids have been described, many of them with relevant therapeutic properties such as morphine, codeine, papaverine and noscapine. Heroin, a semi-synthetic drug produced from morphine is a worldwide serious cause of morbidity and mortality. Heroin dependence is complex phenomenon with environmental and genetic influence, and several biomarkers of exposure have been proposed. This work aims to review the metabolism and metabolomics of opiates with particular interest on their relevance as potential clinical and forensic antemortem and postmortem biomarkers. It is known that the heroin is mainly a prodrug that is rapidly deacetylated in blood to its active metabolite, 6-acetylmorphine, which is then subsequently slowly deacetylated to morphine. Therefore, 6-acetylmorphine has been used as the main target metabolite to prove heroin abuse in clinical, but mostly in forensic routine. Nevertheless, its applicability is limited due to the reduced detection window. Therefore, morphine (and its metabolites morphine-3-glucuronide and morphine-6-glucuronide), codeine, codeine-6-glucuronide, 6-acetylcodeine, noscapine (and its metabolites meconine, desmethylmeconine, and cotarnine), papaverine (and its metabolites 6-desmethylpapaverine, hydroxypapaverine, dihydroxypapaverine, 6-desmethylpapaverine-glucuronide) and thebaine (and acetylthebaol and the non-acetylated analog thebaol) have been additionally recommended to obtain the most reliable results possible. More recently, the identification by metabolomics analysis of several endogenous compounds offered an alternative approach of significant importance to uncover toxic effects. Profound alterations in the neurotransmitters levels and energy and amino acid metabolism have been reported with l-tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetate being suggested as potential non-specific biomarkers of long-term heroin addiction. These endogenous metabolic profiles and exogenous components that together comprise the exposome will certainly help to uncover metabolic disturbances and patterns that may be associate to addiction with relevant clinical and forensic implications.

Topics: Analgesics, Opioid; Biomarkers; Codeine; Forensic Toxicology; Heroin; Humans; Metabolomics; Molecular Structure; Morphine; Opiate Alkaloids; Opioid-Related Disorders

Vaccines offer a promising therapeutic strategy to treat substance use disorders (SUD). Vaccines have shown extensive preclinical proof of selectivity, safety, and efficacy against opioids, nicotine, cocaine, methamphetamine, and designer drugs. Despite clinical evaluation of vaccines targeting nicotine and cocaine showing proof of concept for this approach, no vaccine for SUD has yet reached the market. This review first discusses how vaccines for treatment of opioid use disorders (OUD) and reduction of opioid-induced fatal overdoses fit within the current medication assisted treatment (MAT) portfolio, and then summarizes ongoing efforts toward translation of vaccines targeting heroin, oxycodone, fentanyl, and other opioids. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.

Topics: Antigen-Antibody Complex; Blood-Brain Barrier; Drug Overdose; Fentanyl; Heroin; Humans; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders; Oxycodone; Vaccines

Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized.. Information was obtained by searching PubMed, governmental agency websites, and conference proceedings.. Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population.. Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy.

Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Opioid-Related Disorders; Prescription Drugs; Substance-Related Disorders

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

The opioid epidemic is associated with morbidity and mortality, and it has taken a vast toll on American society. While prescription opioid abuse is part of the opioid problem, it is by no means the entirety of it. Opioid abuse appears to have entered a technology-driven new world of clandestine labs all over the globe and many new synthetic analog, counterfeit, and adulterated drugs that arrive via the internet faster than the Drug Enforcement Administration (DEA) can catalog and outlaw them. To deal with opioid abuse, it must be recognized that it is more - far more - than a subset of chronic pain patients who become addicted. Indeed, to reduce the opioid epidemic to this population is to misunderstand it. The opioid epidemic involves illicit opioids, counterfeit opioids, new psychoactive substances, diverted opioids, and prescription opioids. The objective of this narrative review is to consider the roles of all substances that contribute to the opioid epidemic in America.

Topics: Analgesics, Opioid; Epidemics; Fentanyl; Heroin; Humans; Illicit Drugs; Opioid-Related Disorders; Psychotropic Drugs; United States

Despite the availability of effective medications and psychosocial interventions for the management of a substance use disorder, some individuals repeatedly fail the most aggressive treatment regimens. For such individuals, alternative treatment options exist seeking to mitigate the negative consequences of the use of harmful substances. Participation in a managed alcohol program, or the use of sustained-release oral morphine or injectable opioid agonist treatment or the creation of safe injecting facilities, are examples of such nonstandard approaches. This article reviews the available evidence of these treatment modalities.

Topics: Alcohol-Related Disorders; Analgesics, Opioid; Delayed-Action Preparations; Heroin; Humans; Morphine; Opioid-Related Disorders; Public Housing; Randomized Controlled Trials as Topic; Severity of Illness Index

Since the 1990s, there have been seven clinical trials, and considerable clinical experience, in supervised injectable opioid treatment (SIOT) for individuals who, despite previous treatments, continue to inject illicit heroin and experience harmful health and social consequences. Most studies prescribed pharmaceutical heroin (diacetyl morphine, or DAM). This paper critically reviews randomised trials, long-term follow-up studies and qualitative reports of SIOT, and briefly reviews evidence regarding other medications used in injectable treatment as an alternative to DAM. It seeks to identify critical, unresolved issues regarding this treatment. Randomised trials comparing DAM with oral methadone (OM) report that while in treatment, participants randomised to DAM used less street heroin; reported spending less money on drugs, committed fewer crimes, and experienced improved health. Similar findings pertain to SIOT with hydromorphone. Because of the risks of overdose, diversion, and misuse, all recent trials of injected DAM involved supervised administration. This contributes to treatment being expensive to deliver. There is conflicting evidence regarding societal cost effectiveness, with some studies estimating that the reduction in crime more than compensates for the expense of the treatment. The critical, unresolved issues concerning this modality of treatment relate to the way in which it is approached-either as a medium-term, intensive intervention where other treatment has failed, designed to bring people into conventional opioid agonist treatment (OAT); or an indefinite support aimed at reducing social and personal harm. The former seems in line with the available findings on long-term effectiveness of SIOT and might be more acceptable given its rather moderate cost.

Topics: Analgesics, Opioid; Drug Overdose; Follow-Up Studies; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance-Related Disorders; Treatment Outcome

Opioid overdose is a major cause of mortality, but injury and fatal outcomes can be prevented by timely administration of the opioid antagonist naloxone. Pre-provision of naloxone to opioid users and family members (take-home naloxone, THN) was first proposed in 1996, and WHO Guidelines were issued in 2014. While widespread in some countries, THN is minimally available or absent elsewhere. This review traces the development of THN over twenty years, from speculative harm reduction proposal to public health strategy.. Medline and PsycINFO were searched for peer-reviewed literature (1990-2016) using Boolean queries: 1) "naloxone OR Narcan"; 2) "(opioid OR opiate) AND overdose AND prevention". Grey literature and specialist websites were also searched. Data were extracted and synthesized as narrative review, with key events presented as chronological timeline.. Results are presented in 5-year intervals, starting with the original proposal and THN pilots from 1996 to 2001. Lack of familiarity with THN challenged early distribution schemes (2001-2006), leading to further testing, evaluation, and assessment of challenges and perceived medicolegal barriers. From 2006-2011, response to social and legal concerns led to the expansion of THN programs; followed by high-impact research and efforts to widen THN availability from 2011 to 2016.. Framed as a public health tool for harm reduction, THN has overcome social, clinical, and legal barriers in many jurisdictions. Nonetheless, the rising death toll of opioid overdose illustrates that current THN coverage is insufficient, and greater public investment in overdose prevention will be required if THN is to achieve its full potential impact.

Topics: Analgesics, Opioid; Drug Overdose; Family; Heroin; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Peer Group; Time Factors

Fentanyl and non-pharmaceutical fentanyls (NPFs) have been responsible for numerous outbreaks of overdoses all over the United States since the 1970s. However, there has been a growing concern in recent years that NPFs are contributing to an alarming rise in the number of opioid-related overdoses.. The authors conducted a narrative review of the published and grey literature on fentanyl and NPFs in PubMed, Google Scholar, and Google using the following search terms: "fentanyl", "non-pharmaceutical fentanyl", "fentanyl analogs", "fentanyl laced heroin" and "fentanyl overdose". References from relevant publications and grey literature were also reviewed to identify additional citations for inclusion.. The article reviews the emergence and misuse of fentanyl and NPFs, their clinical pharmacology, and the clinical management and prevention of fentanyl-related overdoses.. Fentanyl and NPFs may be contributing to the recent rise in overdose deaths in the United States. There is an urgent need to educate clinicians, researchers, and patients about this public health threat.

Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Opioid-Related Disorders; United States

Retention in medication-assisted treatment among opiate-dependent patients is associated with better outcomes. This systematic review (55 articles, 2010-2014) found wide variability in retention rates (i.e., 19%-94% at 3-month, 46%-92% at 4-month, 3%-88% at 6-month, and 37%-91% at 12-month follow-ups in randomized controlled trials), and identified medication and behavioral therapy factors associated with retention. As expected, patients who received naltrexone or buprenorphine had better retention rates than patients who received a placebo or no medication. Consistent with prior research, methadone was associated with better retention than buprenorphine/naloxone. And, heroin-assisted treatment was associated with better retention than methadone among treatment-refractory patients. Only a single study examined retention in medication-assisted treatment for longer than 1 year, and studies of behavioral therapies may have lacked statistical power; thus, studies with longer-term follow-ups and larger samples are needed. Contingency management showed promise to increase retention, but other behavioral therapies to increase retention, such as supervision of medication consumption, or additional counseling, education, or support, failed to find differences between intervention and control conditions. Promising behavioral therapies to increase retention have yet to be identified.

Topics: Behavior Therapy; Buprenorphine; Heroin; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

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

Opioid abuse in humans is characterized by discontinuous periods of drug use and abstinence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of heroin addicts. The major problem in the treatment of opioid dependence still remains the occurrence of relapse, to which stressful life events, renewed use of heroin, and exposure to drug-associated environmental cues are all positively correlated. To study the neurobiology of relapse, many research groups currently use the reinstatement animal model, which greatly contributed to disentangle the mechanisms underlying relapse to drug-seeking in laboratory animals. The use of this model is becoming increasingly popular worldwide, and new versions have been recently developed to better appreciate the differential contribution of each opioid receptor subtype to the relapse phenomenon. In this chapter we review the state of the art of our knowledge on the specific role of the opioid receptors as unrevealed by the reinstatement animal model of opioid-seeking behavior.

Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Disease Models, Animal; Heroin; Humans; Opioid-Related Disorders; Receptors, Opioid; Substance-Related Disorders

Opioid dependence is associated with high levels of morbidity, yet sparse data exists regarding the health-related quality of life (HRQoL) of individuals with opioid dependence, particularly following treatment initiation. To inform cost-effectiveness analyses of treatment modalities, this study investigates short-term changes in HRQoL following enrollment into opioid agonist treatment (OAT), across treatment modalities and patient subgroups.. Data was analyzed from the Starting Treatment with Agonist Replacement Therapies (START) and Prescription Opioid Addiction Treatment Studies (POATS) randomized controlled trials. Participants included individuals dependent on prescription opioids (POs) or heroin, receiving limited-term or time-unlimited treatment. PO- or heroin-users in START received buprenorphine/naloxone (BUP/NX) or methadone (MET) over 24 weeks. PO-users in POATS received psychosocial care and short-term (4-week) taper with BUP/NX, with non-responders offered subsequent extended (12-week) stabilization and taper. HRQoL was assessed using the short-form SF-6D while in and out of OAT, with distinction between MMT and BUP/NX in START. Linear mixed effects regression models were fitted to determine the independent effects of OAT on HRQoL and characterize HRQoL trajectories.. Treatment had a similar immediate and modest positive association with HRQoL in each patient subgroup. The association of OAT on HRQoL was statistically significant in each model, with effect sizes between 0.039 (heroin-users receiving BUP/NX) and 0.071 (PO-users receiving MET). After initial improvement, HRQoL decreased slightly, or increased at a diminished rate.. OAT, whether delivered in time-limited or unlimited form, using BUP/NX or MET, is associated with modest immediate HRQoL improvements, with diminishing benefits thereafter.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cost-Benefit Analysis; Female; Health Status; Heroin; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Randomized Controlled Trials as Topic

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

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

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

This review primarily focuses on our recent findings in bidirectional translational research on opiate and cocaine addictions. First, we present neurobiological and molecular studies on endogenous opioid systems (e.g. proopiomelanocortin, mu opioid receptor, dynorphin, and kappa opioid receptor), brain stress-responsive systems (e.g. orexin, arginine vasopressin, V1b receptor, and corticotropin-releasing factor), hypothalamic-pituitary-adrenal axis, and neurotransmitters (especially dopamine), in response to both chronic cocaine or opiate exposure and to drug withdrawal, using several newly developed animal models and molecular approaches. The second aspect is human molecular genetic association investigations including hypothesis-driven studies and genome-wide array studies, to define particular systems involved in vulnerability to develop specific addictions, and response to pharmacotherapy.

Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Cocaine; Genome-Wide Association Study; Heroin; Humans; Ligands; Methadone; Narcotics; Opioid-Related Disorders; Pharmacogenetics; Receptors, Opioid

To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients.. The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid dependence. Findings show not only efficacy with respect to improvement of health, reduction of illicit drug use, reduction of criminality and stabilization of social conditions, but also cost effectiveness in the treatment of chronic treatment-resistant heroin addicts.. Agonist maintenance treatment has become the first-line treatment for chronic opioid dependence. High-quality studies demonstrate the effectiveness of a growing number of different agonist maintenance treatments for opioid dependence such as methadone and buprenorphine. In addition, there is new evidence for the effectiveness of other agonists, mainly slow-release morphine, intravenous and inhalable diamorphine and possibly oral diamorphine. Maintenance treatment with intravenous or inhalable diamorphine should be implemented into the healthcare system to treat a group of severely dependent treatment-resistant patients. Furthermore, the opioid-dependent patients not under treatment need to be engaged in maintenance treatments through other harm reduction measures. Agonist maintenance treatment is very effective in stabilizing the health condition and social situation, while also reducing harm, thereby increasing life expectancy and quality of life.

Topics: Buprenorphine; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Heroin; Humans; Methadone; Morphine; Narcotics; Opioid-Related Disorders; Quality of Life

Presently, there is a considerable interest in heroin-assisted treatment: co-prescription of heroin to certain subgroups of chronic, treatment-resistant, opioid dependent patients. In 2002, nine countries had planned (Australia, Belgium, Canada, France, Spain) or ongoing (Germany, The Netherlands, Switzerland, United Kingdom) clinical trials on this subject. These trials (and the routine heroin-assisted treatment programs that might result) will need pharmaceutical heroin (diacetylmorphine) to prescribe to the patients. Research into the development of pharmaceutical forms of heroin for prescription to addicts can benefit from the large amount of knowledge that already exists regarding this substance. Therefore, in this paper we review the physicochemical and pharmaceutical properties of diacetylmorphine and the clinically investigated routes of administration, as well as routes of administration utilised on the street in the context of developing pharmaceutical heroin formulations for prescription to addicts. Patient acceptability of the formulation is essential, because heroin-assisted treatment is aimed at treatment-resistant addicts, who often have to be encouraged to participate (or to maintain participation) in a treatment program. This means that the most suitable products would have pharmacokinetic profiles mimicking that of diacetylmorphine for injection, with rapid peak concentrations of diacetylmorphine and 6-acetylmorphine, ensuring the 'rush effect' and the sustained presence of morphine(-6-glucuronide) creating the prolonged euphoria. Diacetylmorphine for inhalation after volatilisation (via 'chasing the dragon') seems to be a suitable candidate, while intranasal and oral diacetylmorphine are currently thought to be unsuitable. However, oral and intranasal delivery systems might be improved and become suitable for use by heroin dependent patients.

Topics: Analgesics, Opioid; Drug Administration Routes; Drug Administration Schedule; Drug Prescriptions; Drug Resistance; Heroin; Humans; International Cooperation; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Technology, Pharmaceutical

Injection drug use (involving the injection of illicit opiates) poses serious public health problems in many countries. Research has indicated that injection drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis B and C, and drug-related mortality, as well as increased criminal activity. Methadone maintenance treatment is the most prominent form of pharmacotherapy treatment for illicit opiate dependence in several countries, and its application varies internationally with respect to treatment regulations and delivery modes. In order to effectively treat those patients who have previously been resistant to methadone maintenance treatment, several countries have been studying and/or considering heroin-assisted treatment as a complementary form of opiate pharmacotherapy treatment. This paper provides an overview of the prevalence of injection drug use and the opiate dependence problem internationally, the current opiate dependence treatment landscape in several countries, and the status of ongoing or planned heroin-assisted treatment trials in Australia, Canada and certain European countries.

Topics: Australia; Canada; Clinical Trials as Topic; Crime; Europe; Heroin; Humans; Methadone; Opioid-Related Disorders; Public Health; Substance Abuse, Intravenous

Heroin therapeutic prescription to opiate drug addicts through a study of the literature on this topic is valued. Some doubts are put forward with the regard to the scientific quality of the studies, disposable nowdays, on the basis of the experiences of United Kingdom and Switzerland. We are expecting longer and finer studies to answer the question whether this kind of intervention is really useful.

Topics: England; Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders; Switzerland

Due to increasing public health and social issues as secondary problems of opiate dependence (e.g. mortality, risk of HIV- and hepatitis infection, high rate of criminal activities) heroin prescription to opiate addicts has been suggested. Scientific data do not yet allow a solid evaluation of this treatment. As generally accepted, the main criteria for an ethical evaluation of new treatments are a) beneficence (duty to help patients further their important and legitimate interests), b) respect for the patient's autonomy and c) social justice in the allocation of the limited resources of the health care system. Ethical problems of heroin prescription relate to the differentiation between medical concern for the individual patient's health and the public interests in reducing social problems, the problematic capability of addicts of a balanced evaluation of heroin prescription and economic considerations of the costs of heroin prescription in comparison with other forms of treatment of opiate addiction, especially methadone maintenance treatment.

Topics: Contraindications; Drug and Narcotic Control; Ethics, Medical; Freedom; Germany; Health Care Rationing; Heroin; Humans; Narcotics; Opioid-Related Disorders; Patient Advocacy; Rehabilitation

Topics: Controlled Clinical Trials as Topic; Heroin; Humans; Opioid-Related Disorders; Switzerland

Topics: Cocaine-Related Disorders; Cohort Studies; Heroin; Humans; Narcotics; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Social Adjustment; Substance Abuse, Intravenous; Switzerland; Treatment Outcome

We undertook a number of meta-analyses to estimate more precisely the relationship between neonatal mortality and use of opiates in three groups of women. First, women who continued to use illicit heroin throughout pregnancy; secondly, women stabilized on methadone at the time of conception or shortly after and thirdly, women who use heroin well into pregnancy with late entry into methadone treatment, or who continued to use illicit heroin during pregnancy while receiving methadone.. The pooled estimates of the relative risks of neonatal mortality for separate heroin and methadone use were both near unity: 1.47 (95% CI 0.88-2.33) and 1.75 (95% CI 0.60-4.59), respectively. The result for heroin may be due to the inclusion in the meta-analysis of a particularly large study, which, unlike the two other smaller studies included found a relative risk near unity. When this study was excluded from the meta-analysis the pooled estimate of the relative risk of neonatal mortality for heroin use was 3.27 (95% CI 0.95-9.60). In contrast to the results for use of methadone only, the pooled relative risk associated with heroin and methadone use was 6.37 (95% CI 2.57-14.68).. The increased relative risk for neonatal mortality associated with women using heroin and methadone during pregnancy, compared to those stabilized on methadone, is probably due to the chaotic and high-risk life-style associated with illicit heroin use and not solely to the use of heroin and methadone per se. It is recommended tht women who use heroin well into pregnancy with late entry into methadone treatment, or who continue to use illicit heroin during pregnancy while receiving methadone, receive special attention over and above that provided to women stabilized on methadone.

Topics: Female; Heroin; Humans; Infant Mortality; Infant, Newborn; Methadone; Narcotics; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Risk

Neurobiological and behavioral studies, as well as basic and applied clinical research studies, may all contribute to the development of a pharmacotherapy for a specific addictive disease. This paper reviews recent findings from research work, primarily from one laboratory along with collaborative laboratories, that could have some relevance for the development of pharmacotherapy for cocaine dependency. The much earlier experiences of this laboratory in the development of a pharmacotherapy for opiate addiction will be addressed in the context of providing both some specific suggestions for addictive disease pharmacotherapy development and some warnings about the complexities of the introduction and implementation of a pharmacotherapy once developed. Finally, based on both the earlier perspectives and the more recent research findings, some very specific, though speculative, suggestions will be made about the development of novel pharmacotherapies for early opiate addiction, especially for cocaine abuse or addiction and prevention of relapse to cocaine use. The complex and diverse nature of the challenge for pharmacotherapy for the addictive diseases is presented, including specifically a mandate for broadening educational efforts concerning the basis of addictive diseases and the need for treatment, in parallel with the scientific efforts to develop increasingly sophisticated and targeted pharmacotherapies.

Topics: Animals; Cocaine; Drug Therapy; Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders

AIMS/DESIGN: Reduction in mean birth weight and increased incidence of low birth weight are both associated with exposure to illicit heroin in pregnancy. Many studies examining neonatal outcomes in pregnant heroin users treated with methadone report improvements in birth weight. As a consequence, methadone treatment has become the 'gold standard' for the management of the pregnant heroin user. However, not all studies report significant birth weight increases associated with methadone. We undertook a number of meta-analyses on reduction in mean birth weight and incidence of low birth weight to estimate more precisely the effect of illicit heroin and methadone.. Results showed mean reduction in birth weight associated with heroin use: 489 g (95% CI 284-693 g), compared with methadone: 279 g (229-328 g). Similarly, the pooled relative risk estimate for low birth weight for maternal heroin use was 4.61 (95% CI 2.78-7.65), compared with 1.36 (0.83-2.22) for methadone. Analysis of data on combined heroin and methadone use produced a pooled mean reduction in birth weight of 557 g (403-710 g), with a pooled relative risk estimate for low birth weight of 3.28 (2.47-4.39). Pooling 'any' methadone data, regardless of heroin use, produced an estimated reduction in birth weight of 395 g (311-478 g) and a relative risk estimate for low birth weight of 1.90 (1.29-2.81). Combining all data in an 'any' opiate use analysis also produced a mean reduction in birth weight of 483 g (386-583 g) and a relative risk estimate for low birth weight of 3.81 (2.57-5.65).. The current findings suggest that heroin use while receiving methadone may counteract the birth weight advantage gained from methadone alone. Whether this is due to fetal exposure to heroin plus methadone, to reduced antenatal care, other behavioural and environmental factors associated with concurrent use of heroin and methadone or a combination of these is unclear. Nevertheless, these results challenge the current belief that the pregnant user is always better off receiving methadone than not, and suggests that methadone may not be the appropriate treatment for the pregnant women who continue to use illicit heroin.

Topics: Birth Weight; Female; Heroin; Humans; Infant, Low Birth Weight; Infant, Newborn; Methadone; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

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

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

Buprenorphine/naloxone (BUP-NX) and methadone are used to treat opioid use disorder (OUD), yet there is insufficient evidence on the impact of doses on interventions' effectiveness and safety when treating OUD attributable to other opioids than heroin.. We explored associations between methadone and BUP-NX doses and treatment outcomes using data from OPTIMA, a 24-week, pragmatic, open-label, multicenter, pan-Canadian, randomized controlled, two-arm parallel trial with participants (N = 272) with OUD who primarily use opioids other than heroin. Participants were randomized to receive flexible take-home BUP-NX (n = 138) or standard supervised methadone treatment (n = 134). We examined associations between highest BUP-NX and methadone doses, and (1) percentage of opioid-positive urine drug screens (UDS); (2) retention in the assigned treatment; and (3) adverse events (AEs).. The mean (SD) highest BUP-NX and methadone dose were 17.31 mg/day (8.59) and 67.70 mg/day (34.70). BUP-NX and methadone doses were not associated with opioid-positive UDS percentages or AEs. Methadone dose was associated with higher retention in treatment (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.010; 1.041), while BUP-NX dose was not (OR: 1.055; 95% CI: 0.990; 1.124). Higher methadone doses (70-110 mg/day) offered higher odds of treatment retention.. Methadone dose was associated with higher retention, which may be related to its full µ-opioid receptor agonism. Future research should notably ascertain the effect of pace of titration on a wide range of outcomes.. Our results extend previous findings of high doses of methadone increasing retention to be applied in our population using opioids other than heroin, including highly potent opioids.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Heroin; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms.. We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran.. Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models.. This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT.. https://en.irct.ir/trial/53578 .

Topics: Adult; Analgesics, Opioid; Heroin; Humans; Iran; Opiate Substitution Treatment; Opioid-Related Disorders; Opium; Randomized Controlled Trials as Topic; Tramadol

Misuse of prescription and synthetic opioids is a primary contributor to the escalating overdose crisis in North America. However, factors associated with nonfatal overdose (NFO) in this context are poorly understood. We examined individual and socio-structural level correlates of NFO among treatment-seeking adults with an opioid use disorder (OUD) not attributed to heroin (nonheroin opioid use disorder [NH-OUD]).. The study drew data from OPTIMA, a pan-Canadian, multicenter, pragmatic, two-arm randomized control trial comparing supervised methadone and flexible take-home dosing buprenorphine/naloxone models of care among adults with NH-OUD conducted between 2017 and 2020. We used bivariable and multivariable logistic regression to determine factors associated with a lifetime history of NFO among participants enrolled in the trial.. Of 267 included participants, 154 (58%) reported a NFO in their lifetime, of whom 83 (55 %) had an NFO in the last 6 months. In multivariable analyses, positive urine drug test (UDT) for methamphetamine/amphetamine (Adjusted Odds Ratio [AOR] = 2.59; 95 % confidence interval [CI]: 1.17-5.80), positive UDT for fentanyl (AOR = 2.31; 95 % CI: 1.01-5.30), receiving income assistance (AOR = 2.17; 95 % CI: 1.18-4.09) and homelessness (AOR = 2.40; 95 % CI: 1.25-4.68) were positively associated with a lifetime history of NFO.. We found a high prevalence of NFO history in treatment-seeking adults with NH-OUD, particularly among participants with certain drug use patterns and markers of socio-structural marginalization at the time of enrollment. Given the known impact of prior NFO on future harms, these findings highlight the need for comprehensive care approaches that address polysubstance use and social determinants of health to mitigate future overdose risk.

Topics: Adult; Analgesics, Opioid; Canada; Drug Overdose; Heroin; Humans; Opioid-Related Disorders

In the Middle East and Asia, illicit opioid use exists across a spectrum between heroin and opium. The impact of primary opioid of choice on opioid agonist treatment retention has not been well evaluated previously, especially for opium tincture, an increasingly popular form of opioid agonist treatment in Iran. This study investigates the relationship between primary opioid of choice, namely heroin or opium, and retention in opium tincture and methadone treatment.. Participants with opioid use disorder (n = 204) were randomised to receive opium tincture or methadone. All participants were categorised as mainly using opium or heroin. Bivariate analyses between treatment retention and primary opioid of choice (P < 0.05) and logistic regression were conducted.. Among the 191 participants included in this analysis, heroin was the primary substance of choice for 135 participants (70.7%) and opium for 56 (29.3%). Bivariate analysis showed that the opium group was more likely to be satisfied with family situation, employed and retained in treatment than the heroin group while less likely to experience incarceration and use multiple substances. When adjusting for covariates, primary opioid of choice was not significantly associated with retention in either methadone or opium tincture treatment arm.. Positive factors, such as employment, housing and family support, seem to collectively explain the higher retention in treatment among those who primarily use opium compared to those who use heroin. To optimise retention in opioid agonist treatment, biopsychosocial care models should be further evaluated to improve psychosocial functioning.

Topics: Analgesics, Opioid; Heroin; Humans; Iran; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Opium

Stigmatization of an opioid addiction acts as a barrier to those seeking substance use treatment. As opioid use and overdoses continue to rise and affect minority populations, understanding the impact that race and other identities have on stigma is pertinent.. This study aimed to examine the degree to which race and other identity markers (i.e., gender and type of opioid used) interact and drive the stigmatization of an opioid addiction. To assess public perceptions of stigma, this research team conducted a randomized, between-subjects case vignette study (N = 1833) with a nation-wide survey. Participants rated a hypothetical individual who became addicted to opioids on four stigma indices (responsibility, dangerousness, positive affect, and negative affect) based on race (White or Black), gender (male or female), and end point (an individual who transitioned to using heroin or who continued using prescription painkillers).. This study provides evidence that information about multiple identities can impact stigmatizing attitudes, which can provide deeper knowledge on the development of health inequities for individuals with an opioid addiction.

Topics: Analgesics, Opioid; Drug Overdose; Female; Heroin; Humans; Male; Opioid-Related Disorders; Social Stigma

Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP.. In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate.. The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse.. National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800).

Topics: Animals; Heroin; Humans; Male; Methadone; Narcotics; Neoplasm Recurrence, Local; Opioid-Related Disorders; Rats; Substance Withdrawal Syndrome

Opioid use disorder occurs worldwide and creates an increasing economic burden and public health crisis. Some problems are associated with using opioid agonists; therefore, there is a need to develop non-opioid treatments to improve acute and long-term opioid withdrawal syndromes.. We will enroll 100 participants with opioid use disorders receiving methadone maintenance treatment at an addiction treatment center and randomly allocate them to an experimental or control group. The experimental group will receive 12 sessions of light needle therapy within 4 weeks, while the control group will receive sham light needle treatment without any laser output. Urinary morphine levels were assessed before and after treatment. Participants will be asked to self-report their number of episodes or days of heroin use and heroin craving/refusal to use heroin in the previous week before and after treatment on a visual analogue scale score of 0 to 10. Quality of life will be reported using the Short Form-12v2 before and after 4 weeks of treatment. Pulse diagnosis and heart rate variability will be evaluated before and after treatment. Baseline patient characteristics will be compared between the groups using the independent t test and the χ2 test. Data between the 2 groups will be compared using generalized estimation equations, and paired t tests.. This study aims to investigate the effect of adjuvant light needle therapy in patients with opioid use disorder on methadone maintenance treatment.

Topics: Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders; Quality of Life; Randomized Controlled Trials as Topic

Lorcaserin, a high-affinity 5-HT. In this 7-week inpatient trial, 12 non-treatment-seeking volunteers (11 males) with moderate-to-severe opioid use disorder were detoxified from opioids. In a randomized cross-over fashion, participants were first stabilized on lorcaserin (10 mg BID) or placebo (0 mg BID). Participants underwent a two-week testing period during which the reinforcing and subjective effects of intranasal oxycodone were examined in verbal choice, cue-exposure, and progressive-ratio choice sessions. The two testing weeks were identical with the exception that during the first week, active oxycodone (10 mg) was available during verbal choice (self-administration) sessions, and during the second week placebo oxycodone was available. Subsequently, participants were stabilized on the other medication condition (placebo or lorcaserin) and underwent the same testing procedures again.. Lorcaserin did not alter oxycodone self-administration. However, lorcaserin had a trend to increase "wanting heroin" when oxycodone was available, and to accentuate oxycodone-induced miosis.. Under the current experimental conditions, lorcaserin at a dose of 10 mg BID did not reliably decrease the abuse liability of oxycodone, even though the study was sufficiently powered (≥80 %) to detect clinically meaningful differences in the main outcome variables between the placebo and active lorcaserin condition. Future research could explore a wider dose range of lorcaserin and oxycodone.

Topics: Administration, Intranasal; Adult; Benzazepines; Choice Behavior; Cross-Over Studies; Cues; Female; Heroin; Humans; Male; Opioid-Related Disorders; Oxycodone; Reinforcement, Psychology; Self Administration; Treatment Outcome

There is growing public health concern around the potential impact of the opioid crisis on efforts to eradicate HIV. This secondary analysis seeks to determine if those who report opioids as their primary problem drug compared to those who report other drugs and/or alcohol differ in engagement in HIV primary care among a sample of hospitalized people with HIV (PWH) who use drugs and/or alcohol, a traditionally marginalized and difficult to engage population key to ending the HIV epidemic.. A total of 801 participants (67% male; 75% Black, non-Hispanic; mean age 44.2) with uncontrolled HIV and reported drug and/or alcohol use were recruited from 11 hospitals around the U.S. in cities with high HIV prevalence from 2012 to 2014 for a multisite clinical trial to improve HIV viral suppression.. A generalized linear model compared those who reported opioids as their primary problem drug to those who reported other problem drugs and/or alcohol on their previous engagement in HIV primary care, controlling for age, sex, race, education, income, any previous drug and/or alcohol treatment, length of time since diagnosis, and study site.. A total of 95 (11.9%) participants reported opioids as their primary problem drug. In adjusted models, those who reported opioids were significantly less likely to have ever engaged in HIV primary care than those who reported no problem drug use (adjusted risk ratio, ARR = 0.84, 95% Confidence Interval, CI 0.73, 0.98), stimulants (ARR = 0.84, 95% CI 0.74, 0.95), and polydrug use but no alcohol (ARR = 0.79, 95% CI 0.68, 0.93). While not statistically significant, the trend in the estimates of the remaining drug and/or alcohol categories (alcohol, cannabis, polydrug use with alcohol, and [but excluding the estimate for] other), point to a similar phenomena-those who identify opioids as their primary problem drug are engaging in HIV primary care less.. These findings suggest that for hospitalized PWH who use drugs and/or alcohol, tailored and expanded efforts are especially needed to link those who report problem opioid use to HIV primary care. Trial registration This study was funded by National Institutes of Health (NIH) grant: U10-DA01372011 (Project HOPE-Hospital Visit as Opportunity for Prevention and Engagement for HIV-Infected Drug Users; Metsch); which is also a registered clinical trial under the Clinical Trials Network (CTN-0049). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Topics: Adult; Alcohol Drinking; Analgesics, Opioid; Drug Users; Female; Heroin; HIV Infections; Hospitalization; Humans; Illicit Drugs; Male; Opioid-Related Disorders; Primary Health Care; Social Marginalization

To determine whether extended-release injectable naltrexone (XR-NTX), incentives for opiate abstinence, and their combination reduce opiate use compared to a usual care control and whether the combination reduces opiate use compared to either treatment alone.. Randomized 2 × 2 single-site controlled trial conducted from November 2012 through May 2016. After a detoxification and oral naltrexone induction, participants were assigned to a Usual Care, Abstinence Incentives, XR-NTX, or XR-NTX plus Abstinence Incentives group for a six-month intervention period.. A model therapeutic workplace where participants could work on automated computer programs that targeted job-skills training for 4 h every weekday for 24 weeks and earn about $10 per hour.. 84 heroin-dependent adults who were unemployed and medically approved for naltrexone. Most participants were male (71.4%), African American (80.1%), and cocaine dependent (71.4%).. The primary outcome measure was the percentage of urine samples negative for opiates that were collected at once weekly assessments (24 per participant) that were not part of the intervention and for which participants were paid $10 for completing.. Participants who attended the workplace provided thrice-weekly urine samples. Abstinence Incentives participants had to provide opiate-free urine samples to maintain maximum pay. XR-NTX participants received one injection every 4 weeks and were required to take injections in order to work and to maintain maximum pay. Usual Care participants were not offered XR-NTX and opiate urinalysis results did not affect pay.. A large percentage (65 of 149; 43.6%) of individuals failed the induction protocol required for randomization and to be eligible to receive XR-NTX. When missing urine samples were considered positive, there was no significant interaction between XR-NTX and Abstinence Incentives. XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (81.3%, SD 39.0%) than XR-NTX participants (64.5%, SD 47.9%; aOR 10.4, 95% CI 1.3-85.5; P = .030). When urine samples were not replaced, there was a significant interaction between XR-NTX and Abstinence Incentives (aOR 77.0, 95% CI 1.3-4432;P = 0.036); XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (99.6%, SD 0.1%) than XR-NTX participants (85.0%, SD 35.7%; aOR 147.6, 95% CI 6.3-3472; P = 0.002), Abstinence Incentives participants (91.9%, SD 27.3%; aOR 121.7, 95% CI 4.8-3067; P =0.004), and Usual Care participants (78.7%, SD 41.0%; aOR 233.4, 95% CI 9.4-5814; P <.001). No other group differences were significant.. XR-NTX plus incentives for opiate abstinence increased opiate abstinence, but XR-NTX alone did not. XR-NTX can promote opiate abstinence when it is combined with incentives for opiate abstinence in a model therapeutic workplace.

Topics: Adult; Black or African American; Cocaine; Delayed-Action Preparations; Female; Heroin; Humans; Injections; Male; Middle Aged; Motivation; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection; Workplace

In a double-blind, non-inferiority randomized controlled trial injectable hydromorphone, a licensed short acting opioid analgesic, was shown to be as effective as diacetylmorphine for the treatment of severe opioid use disorder. An appropriate question is whether hydromorphone offered open-label can attract and retain patients.. This is a retrospective study, using daily prescription data from the Crosstown Clinic in Vancouver, Canada. Treatment retention among participants who had the opportunity to receive open-label injectable hydromorphone for at least 90 consecutive days (n = 108) before having the choice of receiving open-label diacetylmorphine, was compared to their retention outcomes with double-blind injectable opioid agonist treatment (iOAT). McNemar tests analyzed differences in proportions; a conditional logistic model estimated exact odds ratios; Pairwise t-tests analyzed differences in total number of treatment days; and Kaplan-Meier curves and clustered log-rank tests compared time to first 30 continuous days without injectable treatment.. A total of 74 participants (68.5%) were retained in both open-label hydromorphone and double-blind iOAT. Open-label hydromorphone was not significantly associated with lower retention (OR = 0.5; 95% CI: 0.2, 1.1; p = .10). Participants attended a mean of 84.4 (SD = 15.8) days of iOAT in the trial and 80.5 (SD = 22.0) days in open-label hydromorphone (mean difference of -3.9; 95% CI = -8.9, 1.1). Kaplan-Meier curves and log-rank tests were not statistically significant.. As treatment with injectable hydromorphone expands across Canada, our study contributes in a unique manner by providing evidence that the high retention rates observed during the clinical trial were maintained when participants started open-label hydromorphone.

Topics: Analgesics, Opioid; Canada; Double-Blind Method; Heroin; Humans; Hydromorphone; Injections; Opioid-Related Disorders; Patient Acceptance of Health Care; Retrospective Studies

Extended-release naltrexone (XR-NTX) blocks the effects of opioids for 4weeks; however, starting treatment can be challenging because it requires 7 to 10days of abstinence from all opioids. In the present study we identified patient and treatment characteristics that were associated with successful induction onto XR-NTX.. 144 unemployed heroin-dependent adults who had recently undergone opioid detoxification completed self-report measures and behavioral tasks before starting an outpatient XR-NTX induction procedure. Employment-based reinforcement was used to promote opioid abstinence and adherence to oral naltrexone during the induction. Participants were invited to attend a therapeutic workplace where they earned wages for completing jobs skills training. Participants who had used opioids recently were initially invited to attend the workplace for a 7-day washout period. Then those participants were required to provide opioid-negative urine samples and then take scheduled doses of oral naltrexone to work and earn wages. Participants who had not recently used opioids could begin oral naltrexone immediately. After stabilization on oral naltrexone, participants were eligible to receive XR-NTX and were randomized into one of four treatment groups, two of which were offered XR-NTX. Binary and multiple logistic regressions were used to identify characteristics at intake that were associated with successfully completing the XR-NTX induction.. 58.3% of participants completed the XR-NTX induction. Those who could begin oral naltrexone immediately were more likely to complete the induction than those who could not (79.5% vs. 25.0%). Of 15 characteristics, 2 were independently associated with XR-NTX induction success: legal status and recent opioid detoxification type. Participants who were not on parole or probation (vs. on parole or probation) were more likely to complete the induction (OR [95% CI]=2.5 [1.1-5.7], p=0.034), as were those who had come from a longer-term detoxification program (≥21days) (vs. a shorter-term [<21days]) (OR [95% CI]=7.0 [3.0-16.6], p<0.001).. Our analyses suggest that individuals recently leaving longer-term opioid detoxification programs are more likely to complete XR-NTX induction. Individuals on parole or probation are less likely to complete XR-NTX induction and may need additional supports or modifications to induction procedures to be successful.

Topics: Adult; Delayed-Action Preparations; Female; Heroin; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection; Substance Abuse, Intravenous; Unemployment

To determine the effectiveness of injectable hydromorphone and dicaetylmorphine for Indigenous participants in the Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) clinical trial. The study additionally aims to explore the prevalence and frequency of crack cocaine use among subgroups of participants (by gender and ethnicity). This secondary analysis is particularly relevant given the current need for expanded medication assisted treatments for opioid dependence across North America.. Participants self-identifying as First Nations, Métis or Inuit were included in the analysis of Indigenous participants. Six-month treatment outcomes are reported as the difference between diacetylmorphine and hydromorphone treatment arms among Indigenous participants and change from baseline to 6 months in each treatment arm. Differences in outcomes are tested between Indigenous and non-Indigenous participants. Crack cocaine use was explored to determine differences between and within subgroups.. Approximately one-third of SALOME participants self-identified as Indigenous. Indigenous participants presented to treatment with more structural vulnerabilities (e.g. lower education, higher rates of foster care and separation from biological parents) compared to non-Indigenous participants. After 6 months, Indigenous participants in both treatment arms had a significant reduction in days of street heroin use, opioid use, crack cocaine use and illegal activity. Treatment retention did not differ by treatment arm.. Indigenous people that are not engaged by first-line treatments for opioid dependence are in need of effective alternative treatments. Given the political and logistical barriers facing diacetylmorphine, hydromorphone could serve as a more accessible medication to reach and treat this population. [Oviedo-Joekes E, Palis H, Guh D, Marchand K, Brissette S, Lock K, MacDonald S, Harrison S, Anis AH, Krausz M, March DC, Schechter MT. Characteristics and response to treatment among Indigenous people receiving injectable diacetylmorphine or hydromorphone in a randomised controlled trial for the treatment of long-termopioid dependence. Drug Alcohol Rev 2018;37:137-146].

Topics: Adult; Canada; Double-Blind Method; Female; Heroin; Humans; Hydromorphone; Inuit; Male; Middle Aged; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and withdrawal symptoms. The effects of ibudilast on the abuse potential of opioids in humans are largely unknown. The present study was designed to examine the influence of ibudilast on subjective (including drug craving), reinforcing, and analgesic effects of oxycodone in human volunteers diagnosed with opioid dependence (equivalent to moderate-severe opioid use disorder). Non-treatment-seeking opioid-dependent male volunteers (n=11) underwent an in-patient detoxification with morphine, followed by maintenance on placebo (0 mg b.i.d.) and active ibudilast (50 mg b.i.d.). Under each maintenance dose, six experimental sample and choice sessions were completed involving oral oxycodone administration (0, 15, and 30 mg/70 kg, p.o.). Subjective effects of oxycodone and drug craving were measured with visual analog scales (VAS) and a Drug Effects Questionnaire. The cold pressor test was used to produce pain, and a modified progressive-ratio choice procedure was used to measure the reinforcing effects of oxycodone. Under the active ibudilast condition compared with the placebo condition, ratings of drug liking following 15 mg of oxycodone were decreased significantly. The mean drug breakpoint value was also significantly lower in the active vs the placebo ibudilast condition under the 15 mg oxycodone condition, but not significantly lower under the 30 mg oxycodone condition. Heroin craving was significantly reduced under active ibudilast vs placebo, and similar effects were observed for tobacco and cocaine craving. Furthermore, mean subjective ratings of pain were lower in the active ibudilast condition. Our data suggest that ibudilast may be useful for treating opioid use disorders and it may enhance the analgesic effects of oxycodone.

Topics: Analgesics, Opioid; Craving; Heroin; Humans; Male; Middle Aged; Morphine; Opioid-Related Disorders; Oxycodone; Pain; Phosphodiesterase Inhibitors; Pyridines

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

To test whether there are gender differences in treatment outcomes among patients receiving injectable opioids for the treatment of long-term opioid-dependence. The study additionally explores whether men and women have different perceptions of treatment effectiveness.. This study is a secondary analysis from SALOME, a double-blind, phase III, randomized controlled trial testing the non-inferiorirty of injectable hydromorphone to injectable diacetylmorphine among 202 long-term street opioid injectors in Vancouver (Canada). Given this was a secondary analysis, no a priori power calaculation was conducted. Differences in baseline characteristics and six-month treatment outcomes (illicit heroin use, opioid use, crack cocaine use, non-legal activities, physical and psychological health scores, urine positive for street heroin markers, and retention) were analysed by gender using fitted models. Responses to an open ended question on reasons for treatment effectiveness were explored with a thematic analysis.. Men and women differed significantly on a number of characteristics at baseline. For example, women were significantly younger, presented to treatment with significantly higher rates of prior month sex work (31.5% vs. 0%), and used significantly more crack cocaine (14.71 vs. 8.38 days). After six-months of treatment there were no significant differences in treatment outcomes by gender, after adjusting for baseline values. For both men and women, improved health and quality of life were the most common reasons provided for treatment effectiveness, however women were more specific in the types of health improvements.. Despite presenting to treatment with vulnerabilities not faced to the same extent by men, at six-months women did not differ significantly from men in tested trial efficacy outcomes. While the primary outcome in the trial was the reduction of illicit opioid use, in the open-ended responses both men and women focused their comments on improvement in health and quality of life as reasons for treatment effectiveness. The supervised model of care with injectable medications provides a particularly suitable framework for providing care to opioid-dependent men and women not attracted or retained by other treatments. The absence of statistical differences reported in this secondary analysis may be due to lack of adequate statistical power to detect meaningful effects.. This trial is registered with ClinicalTrials.gov (NCT01447212) Registered: October 4, 2011 at the following link: https://clinicaltrials.gov/ct2/show/NCT01447212 .

Topics: Administration, Intravenous; Adult; Analgesics, Opioid; Double-Blind Method; Female; Heroin; Humans; Hydromorphone; Male; Middle Aged; Opioid-Related Disorders; Patient Reported Outcome Measures; Sex Characteristics; Substance Abuse, Intravenous; Treatment Outcome

The Study to Assess Long-term Opioid Medication Effectiveness (SALOME) is a two-stage phase III, single site (Vancouver, Canada), randomized, double blind controlled trial designed to test if hydromorphone is as effective as diacetylmorphine for the treatment of long-term illicit opioid injection. Recruiting participants for clinical trials continues to be a challenge in medical and addiction research, with many studies not being able to reach the planned sample size in a timely manner. The aim of this study is to describe the recruitment strategies in SALOME, which offered appealing treatments but had limited clinic capacity and no guaranteed post-trial continuation of the treatments.. SALOME included chronic opioid-dependent, current illicit injection opioid users who had at least one previous episode of opioid maintenance treatment. Regulatory approvals were received in June 2011 and recruitment strategies were implemented over the next 5 months. Recruitment strategies included ongoing open communication with the community, a consistent and accessible team and participant-centered screening. All applicants completed a pre-screening checklist to assess prerequisites. Applicants meeting these prerequisites were later contacted to commence the screening process.. A total of 598 applications were received over the two-year recruitment period; 130 were received on the first day of recruitment. Of these applicants, 485 met prerequisites; however, many could not be found or were not reached before recruitment ended. For the 253 candidates who initiated the screening process, the average time lapse between application and screening date was 8.3 months (standard deviation [SD] = 4.44) and for the 202 randomized to the study, the average processing time from initial screen to randomization was 25.9 days (SD = 37.48; Median = 15.0).. As in prior trials offering injectable diacetylmorphine within a supervised model, recruiting participants for this study took longer than planned. The recruitment challenges overcome in SALOME were due to the high number of applicants compared with the limited number that could be randomized and treated. Our study emphasizes the value of integrating these strategies into clinical addiction research to overcome study-specific barriers.. ClinicalTrials.gov: NCT01447212.

Topics: Analgesics, Opioid; Double-Blind Method; Female; Heroin; Humans; Hydromorphone; Male; Opioid-Related Disorders; Patient Selection; Substance Abuse, Intravenous; Time Factors

The most widely used maintenance treatment for opioid dependency is substitution with long-acting oral opioids. Treatment with injectable diacetylmorphine provides an opportunity for patients to stabilize and possibly transition to oral treatment, if clinically indicated. The aim of this study was to explore outcomes of individuals that received injectable diacetylmorphine and voluntarily transitioned to oral methadone.. The North American Opiate Medication Initiative was a randomized controlled trial that compared the effectiveness of injectable diacetylmorphine (or hydromorphone) to oral methadone for long-term opioid-dependency. Treatment was provided for 12-months with an additional 3 months for transition and weaning. Participants were followed until 24-months from randomization. Among the participants randomized to injectable treatments, a sub-group voluntarily chose to transition to oral methadone (n = 16) during the treatment period. Illicit heroin use and treatment retention were assessed at 24-months for those voluntarily and involuntarily transitioning (n = 95) to oral methadone.. At 24-months, the group that voluntarily transitioned to oral methadone had higher odds of treatment retention (adjusted odds ratio = 5.55; 95% confidence interval [CI] = 1.11, 27.81; Chi-square = 4.33, df = 1, p-value = 0.037) than the involuntary transition group. At 24-months, the adjusted mean difference in prior 30 days of illicit heroin use for the voluntary, compared to the involuntary group was -5.58 (95% CI = -11.62, 0.47; t-value = -1.83, df = 97.4, p-value = 0.070).. Although the results of this study were based on small groups of self-selected (i.e., non-randomized) participants, our data underlines the critical importance of voluntary and patient-centered decision making. If we had continued offering treatment with diacetylmorphine, those retained to injectable medication may have sustained the achieved improvements in the first 12 months. Diversified opioid treatment should be available so patients and physicians can flexibly choose the best treatment at the time.. NCT00175357.

Topics: Administration, Oral; Adult; Analgesics, Opioid; Confidence Intervals; Female; Heroin; Humans; Injections; Male; Middle Aged; Odds Ratio; Opioid-Related Disorders; Outcome Assessment, Health Care

The North American Opiate Medication Initiative (NAOMI) clinical trial compared the effectiveness of injectable diacetylmorphine (DAM) or hydromorphone (HDM) to oral methadone maintenance treatment (MMT). This study aimed to determine participants' perceptions of treatment delivered in NAOMI.. A qualitative sub-study was conducted with 29 participants (12 female): 18 (62.1%) received injectable DAM or HDM and 11 (37.9%) received MMT. A phenomenological theoretical framework was used. Semi-structured interviews were audio-recorded and transcribed verbatim. A thematic analysis was used over successive phases and was driven by the semantic meanings of the data.. Participants receiving injectable medications suggested that the supervised delivery model was stringent but provided valuable stability to their lives. Females discussed the adjustment required for the clinical setting, while males focused on the challenging clinic schedule and its impact on employment abilities. Participants receiving MMT described disappointment with being randomized to this treatment; however, positive aspects, including the quick titration time and availability of auxiliary services, were also discussed.. Treatment with injectable DAM (or HDM) is preferred by participants and considered effective in reducing the burden of opioid dependency. Engaging patients in research regarding their perceptions of treatment provides a comprehensive assessment of treatment needs and barriers.. NCT00175357.

Topics: Adult; Analgesics, Opioid; Dose-Response Relationship, Drug; Female; Heroin; Humans; Hydromorphone; Injections, Subcutaneous; Male; Methadone; North America; Opioid-Related Disorders; Outcome Assessment, Health Care; Research Design; Young Adult

Craving is viewed as a core feature of substance use disorders and has been shown to predict future drug use, particularly over the short term. Accordingly, craving is often assessed in treatment settings as a marker of risk for subsequent drug use. The identification of the briefest measure that maintains predictive validity is of particular value for both clinical and research settings to minimize assessment burden while maintaining utility for the prediction of use.. Data from a multi-site clinical trial of treatment for prescription opioid dependence were examined to evaluate whether a brief, 3-item craving scale administered each week predicted urine-confirmed self report of prescription opioid use in the subsequent week. Logistic regression models examining the association between craving and presence or absence of opioid use in the following week were conducted, controlling for opioid use in the previous week, treatment condition, and lifetime history of heroin use.. Greater craving was associated with a higher odds of prescription opioid use in the following week. For each one-unit increase on this 10-point scale, the odds of using opioids in the subsequent week was 17% higher. In addition to an item assessing urges, items assessing cue-induced craving and perceived likelihood of relapse in an environment where drugs were previously used contributed uniquely to this association.. A brief measure of prescription opioid craving predicted prescription opioid use among individuals in treatment. This measure offers an efficient strategy to inform the assessment of risk for use in this population.

Topics: Adult; Analgesics, Opioid; Craving; Drug Prescriptions; Female; Heroin; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Self Report; Substance Abuse Treatment Centers; Young Adult

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

Studies indicate that different areas of mental, physical, social and daily life functioning need to be considered in order to improve intervention outcomes in substance user patients. The aim of the study was to assess health-related quality of life (HRQOL) in patients diagnosed with opioid dependence as compared to healthy controls and patients diagnosed with depression and schizophrenia.. A total of 1,015 outpatients diagnosed with opioid dependence were investigated during 12 months of maintenance treatment. HRQOL (MSQoL), addiction (EUROP-ASI), and sociodemographic characteristics were assessed.. HRQOL in opioid dependence improved significantly (p < .001), but was lower as compared to that of healthy controls and patients diagnosed with schizophrenia. HRQOL in opioid dependence comprises addiction-specific aspects, most importantly low material satisfaction, physical health, and social stability.. HRQOL measurement provides valuable information for course and outcome in opioid dependence treatment.

Topics: Adult; Depressive Disorder, Major; Female; Health Status; Heroin; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Quality of Life; Schizophrenic Psychology; Severity of Illness Index; Substance Abuse, Intravenous

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

To evaluate physical and mental health and compare treatment outcomes in opiate-dependent patients substituted either with heroin or methadone.. Twelve-month open-label randomized controlled trial.. Out-patient substitution clinics in seven German cities.. A total of 1015 opiate-dependent individuals.. Opiate Treatment Index-Health Scale Score (OTI), Body Mass Index (BMI), serology for infectious diseases such as hepatitis B, C and human immunodeficiency virus as well as tuberculosis, Karnofsky Performance Scale (KPS), electrocardiogram (ECG), echocardiogram, Symptom Checklist 90-R (SCL-90-R), Global Assessment of Functioning (GAF), Modular System for Quality of Life and study medication-related serious adverse events (SAE).. Improvements were found in both heroin and methadone substituted patients regarding OTI, BMI, KPS, SCL-90-R, and GAF, but they were more pronounced for the heroin group (analysis of variance, all P = 0.000). The frequency of pathological echocardiograms decreased in the heroin group and increased in the methadone group (χ(2) test, <0.05). Markers for infectious diseases and frequencies of pathological ECGs did not differ between baseline and 12 months, or between treatment groups. Study medication-related serious adverse events, all of which were treated successfully, occurred 2.5 times more often in the heroin group. The majority of heroin-related SAEs (41 of 58) occurred within a few minutes of the injections.. The integration of severe injection drug users either in methadone or heroin-assisted maintenance treatment has positive effects on most physical and mental change-sensitive variables, with heroin showing superior results. Due to medication-related adverse events, patients should be observed for 15 minutes after a heroin injection.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Body Mass Index; Echocardiography; Electrocardiography; Female; Germany; Health Status; Health Status Indicators; Heroin; Humans; Male; Mental Health; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Serologic Tests; Severity of Illness Index; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Treatment Outcome; Young Adult

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

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST). In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes.. Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8) was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group.. A total of 232 (92%) and 237 (94%) participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by 149 (60.3%) participants; concerns about the randomization process and the study ending were most commonly reported by participants receiving the oral and injectable medications, respectively.. The higher satisfaction among those receiving medically prescribed injectable diacetylmorphine (or hydromorphone) supports current evidence regarding the attractiveness of this treatment for long-term, opioid-dependent individuals not benefiting sufficiently from other treatments. In addition, the measurement of treatment satisfaction provides valuable information about participants at risk of relapse and in need of additional services.. ClinicalTrials.gov Identifier: NCT00175357.

Topics: Adult; Analgesics, Opioid; Canada; Dose-Response Relationship, Drug; Female; Heroin; Humans; Injections, Subcutaneous; Male; Methadone; Opioid-Related Disorders; Outcome Assessment, Health Care; Patient Satisfaction; Randomized Controlled Trials as Topic; Surveys and Questionnaires

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

Until now, the medical prescription of diamorphine (heroin) has been suggested as suitable for patients who have failed previous maintenance treatments. The aim of this paper is to assess the effects of diamorphine on opioid-dependent patients with no previous maintenance treatment experience (NPME).. The German heroin trial compared diamorphine versus methadone maintenance treatment and included 107 patients with NPME. This paper is a sub-analysis of these patients.. When comparing this subsample with the rest of the participants in the study, large baseline differences were found, showing a more severe drug use profile in patients with NPME. However, no differences were found in terms of treatment outcome and treatment retention. In the subsample with NPME, outcome measures on the reduction of illicit drug use were significantly better under diamorphine compared to methadone treatment, while there was no difference in health outcomes.. Controlled studies are now necessary to examine whether diamorphine treatment could be considered as one of several options in treating severely opioid-dependent patients, regardless of previous maintenance treatment experience.

Topics: Adult; Female; Germany; Heroin; Humans; Male; Medication Adherence; Methadone; Narcotics; Opioid-Related Disorders

To assess the long-term course of the feasibility and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users.. Open-label, prospective cohort study with 2 non-randomly assigned treatment arms: DAM tablets only (n = 128) or DAM tablets combined with injected DAM and/or other opioids (n = 237). The average duration of the observation period was 62 months. Study endpoints were the time to discharge from treatment and the number of serious adverse events.. Both patient groups had a higher than 70% retention rate after the first 48 months of treatment, with similar long-term retention rates (after 8 years both groups had retention over 50%). The physician-verified rate of serious adverse events was 0.01 events per application year among the exclusively oral substitution group (intention-to-treat analysis) during the last year of observation, and 0.005 events per application year in the other group.. Because of their feasibility and safety over years, DAM tablets may be a valuable long-term therapeutic alternative.

Topics: Administration, Oral; Adult; Female; Follow-Up Studies; Heroin; Humans; Injections, Intravenous; Male; Medication Adherence; Opioid-Related Disorders

There is consistent evidence showing women access treatment with more severe substance-related profiles relative to men; however, treatment outcome evaluation shows inconclusive results regarding gender differences. Furthermore, few studies evaluate response by gender.. The present analyses were performed using data from the NAOMI study, an open-label, phase III randomized controlled trial, carried out between 2005 and 2008 in Vancouver and Montreal, Canada. A total of 226 long-term treatment-refractory opioid dependent individuals were randomized to receive injectable diacetylmorphine or oral methadone for 12 months. Patients in both treatment groups were offered psychosocial and primary care services. Main outcomes were retention in addiction treatment at 12 months. Drug use, health, psychosocial adjustment and health-related quality of life were examined at baseline and during treatment, using the European Addiction Severity Index, Maudsley Addiction Profile, SF-6D and EuroQol EQ-5D.. A total of 88 (38.9%) females and 138 (61.1%) males were included in the present analysis. Retention rates among female participants in the diacetylmorphine group were significantly higher than oral methadone (83.3% vs. 47.8%). Males receiving diacetylmorphine improved significantly more than females in physical health, health-related quality of life, and family relations but female participants in the diacetylmorphine group had significantly greater improvements in illicit drug use scores and psychological health compared to females allocated to oral methadone.. Among long-term opioid dependent women who have not benefited sufficiently from available treatments, medically prescribed diacetylmorphine is more effective than oral methadone. Men receiving diacetylmorphine showed more improvements than women.

Topics: Administration, Oral; Adult; Female; Health Status; Heroin; Humans; Injections; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Psychotherapy; Quality of Life; Sex Factors; Statistics, Nonparametric; Treatment Outcome

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

Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance.. To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment.. In an open-label multicentre randomised controlled trial, 1015 people with heroin dependence received a variable dose of injectable heroin (n=515) or oral methadone (n=500) for 12 months. Two response criteria, improvement of physical and/or mental health and decrease in illicit drug use, were evaluated in an intent-to-treat analysis.. Retention was higher in the heroin (67.2%) than in the methadone group (40.0%) and the heroin group showed a significantly greater response on both primary outcome measures. More serious adverse events were found in the heroin group, and were mainly associated with intravenous use.. Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment. Despite a higher risk, it should be considered for treatment resistance under medical supervision.

Topics: Adult; Algorithms; Female; Heroin; Humans; Injections, Intravenous; Logistic Models; Male; Methadone; Narcotics; Opioid-Related Disorders; Psychotherapy; Treatment Outcome

A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady-state heroin treatment for at least 12 months. For safety reasons, there was no crossing-over between heroin injection or inhalation. In a double-blind randomised study, 67-100-150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6-monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS-MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels were inversely related to creatinine clearance. After heroin administration, the reaction time was significantly prolonged with 28+/-5.3 msec. in injecting and 13+/-4.9 msec. in inhaling patients. Cardiovascular changes were only mild after heroin administration. Craving-scores declined immediately after heroin administration in both administration groups. Subjective heroin effect was rated more positively in heroin inhaling than in injecting patients, despite the lower C(max) levels following heroin inhalation. In both

Topics: Administration, Inhalation; Adult; Analgesics, Opioid; Blood Pressure; Double-Blind Method; Heart Rate; Heroin; Humans; Injections, Intravenous; Male; Methadone; Middle Aged; Opioid-Related Disorders; Reaction Time

This study aimed to assess the efficacy of the prescription of intravenous diacetylmorphine (DAM) versus oral methadone with medical and psychosocial support, with a view of improving physical and mental health as well as social integration among socially excluded, opioid-dependent individuals for whom standard treatments have failed.. This study used an open, randomized controlled trial.. This study took place in Granada, Spain.. Sixty-two opioid-dependent participants were randomized, 31 in each treatment group, and 50 of them were analyzed. The participants were recruited directly from the streets, through peer outreach, in well-known meeting places for drug-addicted individuals.. Participants in the experimental group received injected DAM, twice a day, plus oral methadone, once a day, for 9 months. The control group received only oral methadone, once a day. The two groups received an equivalent opioid dosage. The average DAM dosage was 274.5 mg/day (range: 15-600 mg), and an average methadone dosage was 42.6 mg/day (range: 18-124 mg). The daily methadone dosage in the control group was 105 mg/day (range: 40-180 mg). Comprehensive clinical, psychological, social, and legal support was given to both groups.. The following were measured in this study: general health, quality of life, drug-addiction-related problems, nonmedical use of heroin, risk behavior for HIV and HCV, and psychological, family, and social status.. Both groups improved with respect to the total domain assessed. Those in the experimental group showed greater improvement in terms of physical health (the improvement was 2.5 times higher; p = .034) and risk behavior for HIV infection (the improvement was 1.6 times higher; p = .012). In addition, this group decreased its street heroin use from 25 days/month to 8 days/month as seen on the Addiction Severity Index (p = .020), as well as the number of days free from drug-related problems (the improvement was 2.1 times higher; p = .004) or involvement in crime (from 11 days/month to <1 day/month; p = .096 between groups).. These findings support the hypothesis that, under the same conditions, DAM could be safely delivered, in our context. Also, in physical health, HIV risk behavior, street heroin use, and days involved in crime, DAM plus methadone was more efficacious than methadone alone. This implies that this treatment could provide an effective alternative for the treatment of socially excluded, opioid-dependent patients with severe physical and mental health problems because of drug addiction, when all available previous treatments have failed.

Topics: Adult; Counseling; Drug Administration Schedule; Drug Prescriptions; Female; Health Status; Hepatitis B; Hepatitis C; Heroin; HIV Seropositivity; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Risk-Taking; Severity of Illness Index; Social Support

This controlled study examined the efficacy of reinforcement-based therapy (RBT) for producing enhanced abstinence outcomes over 12 months in opioid-dependent patients exiting a brief residential detoxification. Patients were randomly assigned upon completing their medically managed taper (i.e., detoxification) to RBT (N=66) or usual care (N=64) referral to community treatment programs. The 6-month RBT program offered an array of abstinence-based incentives including rent payment for recovery housing, program-led recreational activities and skills training for procuring employment. RBT produced significantly higher self-report and urinalysis-confirmed rates of abstinence from opioids and cocaine relative to usual care at 1 (42% versus 15%) and 3 (38% versus 17%) months during treatment but not at 6 or 12 months after enrollment. The RBT but not the usual care group showed significant increases in the number of days worked and the amount of legal income earned at 3, 6 and 12 months. The results of this randomized study suggest that an intensive reinforcement-based therapy that includes abstinence-based recovery housing is a promising approach; however, further research is needed to determine the role of treatment intensity and the specific efficacy of RBT's component parts.

Topics: Adult; Aftercare; Ambulatory Care; Baltimore; Behavior Therapy; Female; Heroin; Humans; Male; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Reinforcement, Psychology; Residence Characteristics; Substance Abuse Detection; Time Factors

The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group (the mean age differences in 4 groups were not statistically significant). Subjects received buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Days retained in treatment were measured. Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for the 30-mg methadone dose group. Retention in the 8-mg dose group was significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant. Methadone group was significantly better than 1mg buprenorphine dose group (p=.004), but was not significantly different from 3 mg buprenorphine dose group (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses of buprenorphine, and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Heroin; Humans; Iran; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Treatment Outcome

Ten male opiate addicts, who were current heroin injectors, underwent positron emission tomographic (PET) scanning during exposure to a sequence of six alternating drug related and neutral video cues, on two occasions. After the second scan, each subject received heroin or placebo using a randomised single-blind procedure. This design allowed the investigation of patterns of brain activity during a range of self-reported cue evoked emotional states, both in the presence and absence of heroin. Self-reports of 'urge to use' correlated strongly with increased regional blood flow (rCBF) in the inferior frontal and orbitofrontal cortex target regions of the mesolimbic dopaminergic system, implicated in conditioning and reward. 'Urge to use' was also associated with highly significant increased rCBF in the right pre-cuneus, an area associated with episodic memory retrieval, and in the left insula, implicated in the processing of the emotional components of stimuli. Self-reports of feeling 'high' correlated with rCBF activation in the hippocampus, an area relevant to the acquisition of stimulus-associated reinforcement.

Topics: Adult; Analysis of Variance; Behavior, Addictive; Brain; Cues; Heroin; Humans; Linear Models; Male; Narcotics; Opioid-Related Disorders; Tomography, Emission-Computed

This study evaluated plasma buprenorphine concentrations 24-72 h following sublingual administration of a dose of buprenorphine solution, ranging from 16 mg/70 kg to 44 mg/70 kg, administered on a daily or thrice-weekly schedule. Additionally, this study evaluated the effects of different thrice-weekly buprenorphine dose schedules on opiate use and withdrawal symptoms.. Opiate dependent subjects (n = 10) were maintained in an outpatient clinic for two 3-week periods at each of three thrice-weekly buprenorphine dose schedules (providing a weekly total buprenorphine dose of 64, 84 and 112 mg) and for 1 week of a daily buprenorphine dose of 16 mg/70 kg. Plasma samples were obtained 24, 48 and 72 h following administration of buprenorphine. Urine samples were also collected and opiate withdrawal symptoms, agonist effects and the use of heroin, cocaine, alcohol and other drugs, were assessed.. Plasma levels showed a wide range of intra- and inter-subject variability. Nonetheless, higher doses of buprenorphine resulted in higher plasma concentrations at each time point and plasma concentration decreased with time. There were no significant differences in heroin use across dosing. Rates of withdrawal symptoms were low and did not differ across dosing schedules.. In the two highest dose schedules, plasma levels 72 h following the administration of the highest dose and at 48 h after the lower dose, were comparable to plasma concentrations at 24 h following daily administration of 16 mg/70 kg of buprenorphine.

Topics: Administration, Sublingual; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Ethanol; Female; Heroin; Humans; Male; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors

Recent theories of substance abuse have used value discounting of delayed rewards to partly explain the decision to take drugs. Normative-economic theory holds that an exponential function describes the effects of delay on discounting, whereas the matching law posits a hyperbolic discounting function. The ability of these functions to describe 18 human heroin-dependent individuals' monetary- and heroin-reward delay-discounting functions was assessed. In the 1st condition, participants chose between immediate and delayed hypothetical monetary rewards. Delayed rewards were $1,000, and the immediate reward amount was adjusted until choices reflected indifference. In the 2nd condition, participants chose between immediate and delayed heroin (the delayed amount was that which each participant reported he or she could purchase with $1,000). The hyperbolic function produced significantly higher R2 values and significantly lower sums of squared error values. Consistent with previous findings, delayed heroin rewards were discounted at a significantly higher rate than were delayed monetary rewards.

Topics: Adult; Buprenorphine; Female; Heroin; Humans; Male; Motivation; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Reward; Time Factors

This study tested the effectiveness of fluoxetine as a treatment for depression in a population of methadone-maintained opioid addicts. Methadone-maintained opioid addicts (44) with depression received fluoxetine or placebo in addition to their methadone, in a double-blind randomized trial, for 12 weeks. Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo. In addition, drug use outcomes, including cocaine and heroin self-reported use and urine toxicology were measured. There was a significant decrease in heroin use in treatment, but no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint. In separately analyzing data for the subsample of subjects with the most severe depression, there was a significant decrease in depression during treatment and a significant decrease in self-reported cocaine use, but no medication effect on either depressive symptoms or on cocaine use. This study suggests that fluoxetine is not an effective agent in treating depression or cocaine use in this population.

Topics: Adult; Antidepressive Agents, Second-Generation; Behavior, Addictive; Cocaine; Cocaine-Related Disorders; Depression; Depressive Disorder; Double-Blind Method; Female; Fluoxetine; Heroin; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Substance Abuse Detection; Treatment Outcome

In the 1994-1996 trial of medically controlled prescription of narcotics to dependent users, 800 places were ascribed to heroin substitutes and another 200 for methadone and morphine substitutes. The trial was evaluated with the aid of an accompanying research. Among the results demonstrated in the evaluation was an improvement of the health of the participants. The economic assessment was drawn from observations of health effects within a sub-sample of 142 participants from four centers. In a retrospective statistical survey, for each acute illness which could be influenced through the trial, the number of diagnoses was recorded in the first and thirteenth month after study entry. Also, based on a number of representative cases for each of these acute illnesses, the resource use, i.e. the types and numbers of medical products and services rendered to the patients, was recorded. The results showed a clear decline in depressive episodes, skin diseases, digestive system disorders as well as epileptic attacks and intoxication. Treatment costs could be reduced from a total of CHF 94875.--to CHF 21,998.--/month or from CHF 22.27 to CHF 5.15/patient per day. The improvement of somatic and psychic health due to the medically controlled prescription of narcotics resulted in a benefit of CHF 17.11/person per day.

Topics: Depression; Digestive System Diseases; Drug Prescriptions; Epilepsy; Health Care Costs; Heroin; Humans; Methadone; Morphine Derivatives; Narcotics; Opioid-Related Disorders; Retrospective Studies; Skin Diseases

Delay discounting was investigated in opioid-dependent and non-drug-using control participants. The latter participants were matched to the former on age, gender, education, and IQ. Participants in both groups chose between hypothetical monetary rewards available either immediately or after a delay. Delayed rewards were $1,000, and the immediate-reward amount was adjusted until choices reflected indifference. This procedure was repeated at each of 7 delays (1 week to 25 years). Opioid-dependent participants were given a second series of choices between immediate and delayed heroin, using the same procedures (i.e., the amount of delayed heroin was that which could be purchased with $1,000). Opioid-dependent participants discounted delayed monetary rewards significantly more than did non-drug-using participants. Furthermore opioid-dependent participants discounted delayed heroin significantly more than delayed money.

Topics: Adolescent; Adult; Female; Heroin; Humans; Impulsive Behavior; Male; Narcotics; Opioid-Related Disorders; Personality Tests; Reward

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

The authors compared the effects of acetorphan, an enkephalinase inhibitor, with those of clonidine for the treatment of the opioid withdrawal syndrome. Nineteen patients addicted to heroin or synthetic opiates who were undergoing drug withdrawal and displayed a withdrawal syndrome according to DSM-III criteria were studied for 5 days in a hospital setting. In a double-blind trial, 10 subjects were given acetorphan intravenously and nine were given clonidine; objective signs and subjective symptoms of withdrawal were recorded.. On several objective signs, the effect of acetorphan was more marked than that of clonidine, whereas the two drugs exhibited similar efficacy with respect to the subjective components of withdrawal. No side effect was noted in the subjects who received acetorphan.. Enkephalinase inhibition may constitute a novel and safe therapeutic approach to the opioid withdrawal syndrome.

Topics: Adolescent; Adult; Clonidine; Double-Blind Method; Female; Heroin; Humans; Male; Narcotics; Neprilysin; Opioid-Related Disorders; Substance Withdrawal Syndrome; Thiorphan

Topics: Administration, Oral; Adult; Double-Blind Method; Heroin; Humans; Methadone; Opioid-Related Disorders; Random Allocation; Substance Withdrawal Syndrome

1 This study was performed because dose-related effects of heroin on human sleep had not been described previously, and to discover if heroin produces a morphine-like insomnia. 2 After three adaptation nights, the sleep of seven male nondependent opiate addicts was studied following i.m. doses of heroin (3, 6, 12 mg/70 kg), morphine (10, 20 mg/70 kg) or placebo at weekly intervals in a randomized double-blind crossover design. 3 Heroin produces a dose-related increase in wakefulness, drowsiness episodes, muscle tension, and shifts in sleep-waking states. 4 Heroin produces a dose-related decrease in total sleep, sleep efficiency, delta sleep and REM sleep (REMS). 5 Heroin is about twice as potent as morphine in producing this type of insomnia. 6 'Morphine insomnia' appears to be a characteristic initial effect of several opioids, at least in nondependent opiate addicts, and might serve as a model insomnia for evaluation of hypnotics.

Topics: Adult; Arousal; Heroin; Humans; Male; Morphine; Opioid-Related Disorders; Sleep Initiation and Maintenance Disorders; Sleep, REM

People who inject drugs (PWID) have an elevated risk of fentanyl-related overdoses. This study explores fentanyl overdose concerns among PWID and the role of sex, racial minority status, and overdose prevention efforts in these concerns.. Data were from 498 PWID from Baltimore City, MD, recruited using street-based outreach between 2016 and 2019. Multinomial logistic regressions assessed correlates of participants' level of concern for themselves and their peers overdosing from fentanyl.. A third of participants were female, half were Black, over two-thirds perceived fentanyl to be in all/most of heroin, 40% expressed low fentanyl overdose concern, and a third overdosed in the past 6 months. After controlling for sociodemographic characteristics, female sex was associated with being very concerned about fentanyl overdoses for oneself (adjusted relative risk [aRR]: 2.13; 95% CI: 1.22, 3.72) and peers (aRR: 1.98; 95% CI: 1.14, 3.45). Compared to Black participants, White participants were less likely to be very concerned about fentanyl overdoses for themselves (aRR: 0.35; 95% CI: 0.19, 0.65). Participants who often/always carried naloxone (aRR: 2.91; 95% CI: 1.42, 5.95) perceived fentanyl in most heroin (aRR: 2.78; 95% CI: 1.29, 5.97) or were on medications for opioid use disorder (MOUD) (quite a bit concerned aRR: 2.18; 95% CI: 1.28, 3.69; very concerned: aRR: 1.96; 95% CI: 1.19, 3.22) were more likely than their counterparts to report being concerned for their peers, but not for themselves.. Female sex and racial minority status were associated with greater concern regarding fentanyl overdoses for oneself. Increasing overdose deaths in these populations suggests disparate access to harm-reduction initiatives rather than interest or concern. Furthermore, findings on naloxone, MOUD, and concerns for peers support social network-based interventions among PWID. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Topics: Analgesics, Opioid; Drug Overdose; Drug Users; Ethnic and Racial Minorities; Female; Fentanyl; Heroin; Humans; Male; Naloxone; Opioid-Related Disorders; Substance Abuse, Intravenous

Opioid dependence is causing an epidemic in the US, but unlike the 1970s it seems more related to prescription opioids than heroin.. The objective of this study is to assess whether this new epidemic has already reached our environment and to see if there are changes in consumption and in the characteristics of consumers.. Retrospective cross-sectional study. 1,140 patients were included between 2012 and 2019, 633 of whom were first visits to Drug Addiction Care and (CAS) Monitoring Centers, 502 corresponding to emergency room visits for problems related to overdose or withdrawal of heroin or opioids with prescription, and the remaining 5 are newborns of mothers addicted to heroin. Demographic data and characteristics of the substances of abuse were analyzed, comparing between partial periods.. There was a global decrease in the first visits of patients to the CAS who reported heroin addiction (P=.001), while those addicted to pharmacy opioids have remained stable. There has been an irregular increase in total emergency visits, overdose consultations, and withdrawal consultations, both for heroin and prescription opioids (P=.062, P=.166 and P=.005, respectively). Opioid-related emergencies have been less frequent than for heroin. Non-Spanish European patients have increased compared to Spanish patients.. There has been no worrying increase in heroin or prescription opioid abuse in our setting.

Topics: Analgesics, Opioid; Cross-Sectional Studies; Drug Overdose; Heroin; Humans; Infant, Newborn; Opioid-Related Disorders; Population Groups; Retrospective Studies

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 μm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.

Topics: Analgesics, Opioid; Animals; Brain; Diffusion Tensor Imaging; Female; Heroin; Humans; Mice; Mice, Inbred C57BL; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects

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

Illicit substance use is common among people entering prisons, as is returning to substance use after release from prison. We aimed to assess the predictive validity of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) for returning to substance use after release from prison.. A longitudinal design with baseline survey conducted between 2008 and 2010 in the 6 weeks before expected prison release and up to three follow-up surveys in the 6 months after release.. Prisons in Queensland, Australia.. A total of 1054 adults within 6 weeks of expected release from prison.. The ASSIST was used to assess problematic use of cannabis, methamphetamine, heroin and other non-prescribed opioids in the 3 months before incarceration. Post-incarceration substance use was measured at 1, 3 and 6 months after release. We calculated the area under the receiver operating characteristic curve (AUROC) and the optimal ASSIST cut-off score for each substance, using Youden's index (J).. Forty-one per cent (n = 434) of the cohort reported any substance use during follow-up: 33% (n = 344) used cannabis, 20% (n = 209) methamphetamine, 10% (n = 109) heroin and 9% (n = 97) illicit other opioids. The optimal ASSIST cut-off score was ≥ 4 for heroin, methamphetamine and cannabis and ≥ 1 for other opioids. Using these cut-offs, the AUROC was highest for heroin in predicting both any use (AUROC = 0.82) and weekly use (AUROC = 0.88) in the past 4 weeks. AUROCs for other drugs ranged from 0.73 to 0.79.. The ASSIST shows promise as an accurate and potentially scalable tool that may be useful for predicting a return to substance use after release from prison and could inform service delivery. The substantial rates of returning to substance use after release from prison suggest that prison serves to interrupt rather than cease substance use.

Topics: Adult; Analgesics, Opioid; Cannabis; Heroin; Humans; Methamphetamine; Opioid-Related Disorders; Prisoners; Prisons; Smoking

(1) Background: Attention deficit hyperactivity disorder (ADHD) is a common comorbid condition in opioid use disorder (OUD) and is associated with a more severe course of substance use. Patients with severe OUD who have not responded to oral opioid maintenance treatment can be treated with intravenous diamorphine up to three times per day. Here, we investigated the prevalence of ADHD among patients undergoing either daily diamorphine maintenance treatment or daily oral opioid maintenance treatment. (2) Methods: We assessed all participants with the WURS-k and the ADHD-SR. The Diagnostic Interview for ADHD in Adults (DIVA) was performed with all participants who met the cut-off in the WURS-k and/or ADHD-SR. (3) Results: The overall prevalence of ADHD was 17.9%. Prevalence of ADHD among patients undergoing daily diamorphine maintenance treatment was 14.3%. Prevalence of ADHD among patients undergoing daily oral opioid maintenance treatment was 20.3%. The combined presentation of ADHD was the most prevalent condition. In urine samples of participants with comorbid ADHD, heroin was detected the most and cocaine the least frequently. (4) Conclusions: Almost one out of five patients with OUD suffered from comorbid ADHD. In 83.3%, ADHD had not been diagnosed prior to participation in this study. Thus, patients with SUD could benefit from being routinely screened for ADHD.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Comorbidity; Heroin; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Prevalence; Substance-Related Disorders

Recessions, poverty, and unemployment have been associated with opioid use. However, these measures of financial hardship may be imprecise, limiting our ability to understand this relationship. We tested associations between relative deprivation and non-medical prescription opioid use (NMPOU) and heroin use among working-age adults (ages 18-64) during the Great Recession. Our sample included working-age adults in the 2005-2013 United States National Survey of Drug Use and Health (n = 320,186). Relative deprivation compared the lowest limit of participants' income category to the national 25th percentile individual income for people with similar socio-demographic characteristics (race and ethnicity, gender, year). We distinguished the period before (1/2005-11/2007), during (12/2007-06/2009), and after (07/2007-12/2013) the Great Recession. We estimated odds of past-year NMPOU and heroin use for each past-year exposure (i.e., relative deprivation, poverty, unemployment) using separate logistic regressions adjusting for individual-level covariates (gender, age, race/ethnicity, marital status, and education) and national-level annual Gini coefficient. Our results show that NMPOU was higher among people experiencing relative deprivation (aOR = 1.13, 95% CI = 1.06-1.20), poverty (aOR = 1.22, 95% CI = 1.16-1.29), and unemployment (aOR = 1.42, 95% CI = 1.32-1.53) between 2005 and 2013, as was heroin use (aORs = 2.54, 2.09, 3.55, respectively). The association between relative deprivation and NMPOU was modified by recession timing, and was significantly higher after the Recession (aOR = 1.21, 95% CI = 1.11-1.33). Relative deprivation was associated with higher odds of NMPOU and heroin use, and higher odds of NMPOU after the Great Recession. Our findings suggest contextual-level factors may modify the relationship between relative deprivation and opioid use, and support the need for new measures of financial hardship.

Topics: Adolescent; Adult; Analgesics, Opioid; Educational Status; Heroin; Humans; Logistic Models; Middle Aged; Opioid-Related Disorders; United States; Young Adult

With the increasing use of non-prescribed buprenorphine (NPB), we need more data to identify the longitudinal patterns of NPB use. The goal of this natural history study is to characterize heterogeneity in trajectories of NPB, other opioid use, and participation in medication for opioid disorder (MOUD) treatment among a community-recruited sample of individuals with current opioid use disorder (OUD).. The study recruited a community-based sample of 357 individuals with OUD who used NPB in the past 6 months in Ohio, United States, for baseline and follow-up assessments (every 6 months for 2 years) of drug use, treatment participation, and other health and psychosocial characteristics. The study used multiple imputation to handle missing data. We used a multi-trajectory latent class growth analysis (MT-LCGA) to find salient groupings of participants based on the trajectories of NPB, other opioid use, and treatment participation.. Over time, NPB use frequency declined from a mean of 14.6 % of days at baseline to 3.6 % of days at 24-month follow-up along with declines in heroin/fentanyl (56.4 % to 23.6 % of days) and non-prescribed pharmaceutical opioid (NPPO) use (11.6 % to 1.5 % of days). Participation in MOUD treatment increased from a mean of 17.0 % of days at baseline to 52.4 % of days at 24 months. MT-LCGA identified a 6-class model. All six classes showed declines in NPB use. Class 1 (28 %) was characterized by high and increasing MOUD treatment utilization. Class 2 (21 %) showed sustained high levels of heroin/fentanyl use and had the lowest levels of NPB use (2.2 % of days) at baseline. Class 3 (3 %) was characterized as the primary NPPO use group. Class 4 (5 %) transitioned from high levels of NPB use to increased MOUD treatment utilization. It had the highest levels of NPB use at baseline (average of 80.7 % of days) that decreased to an average of 12.9 % of days at 24 months. Class 5 (16 %) showed transition from high levels of heroin/fentanyl use to increased MOUD treatment utilization. Class 6 (27 %) showed decreased heroin/fentanyl use over time and low MOUD treatment utilization. Classes showed varying levels of improvement in psychosocial functioning, polydrug use, and overdose risks.. Overall, our findings suggest that NPB use was generally self-limiting with individuals reducing their use over time as some engage in greater utilization of MOUD treatment. A need exists for continuing improvements in MOUD treatment access and retention.

Topics: Analgesics, Opioid; Buprenorphine; Fentanyl; Heroin; Humans; Opioid-Related Disorders

Naloxone distribution is central to ongoing efforts to address the opioid overdose crisis. Some critics contend that naloxone expansion may inadvertently promote high-risk substance use behaviors among adolescents, but this question has not been directly investigated.. We examined relationships between naloxone access laws and pharmacy naloxone distribution with lifetime heroin and injection drug use (IDU), 2007-2019. Models generating adjusted odds ratios (aOR) and 95% confidence intervals (CI) included year and state fixed effects, controlled for demographics and sources of variation in opioid environments (e.g., fentanyl penetration), as well as additional policies expected to impact substance use (e.g., prescription drug monitoring). Exploratory and sensitivity analyses further examined naloxone law provisions (e.g., third-party prescribing) and applied e-value testing to assess vulnerability to unmeasured confounding.. Adoption of any naloxone law was not associated with changes in adolescent lifetime heroin or IDU. For pharmacy dispensing, we observed a small decrease in heroin use (aOR: 0.95 [CI: 0.92, 0.99]) and a small increase in IDU (aOR: 1.07 [CI: 1.02, 1.11]). Exploratory analyses of law provisions suggested that third-party prescribing (aOR: 0.80, [CI: 0.66, 0.96]) and non-patient-specific dispensing models (aOR: 0.78, [CI: 0.61, 0.99]) were associated with decreased heroin use but not decreased IDU. Small e-values associated with the pharmacy dispensing and provision estimates indicate that unmeasured confounding may explain observed findings.. Naloxone access laws and pharmacy naloxone distribution were more consistently associated with decreases rather than increases in lifetime heroin and IDU among adolescents. Our findings therefore do not support concerns that naloxone access promotes high-risk adolescent substance use behaviors. As of 2019, all US states have adopted legislation to improve naloxone access and facilitate use. However, further removal of adolescent naloxone access barriers is an important priority given that the opioid epidemic continues to affect people of all ages.

Topics: Adolescent; Analgesics, Opioid; Drug Overdose; Heroin; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; United States

Heroin-assisted treatment (HAT) is a proven effective treatment option for individuals with severe opioid use disorder (OUD). In Switzerland, pharmaceutical heroin (diacetylmorphine, DAM) is available in tablet form or as injectable liquid. This creates a large barrier for individuals who require the rapid onset of effect but are either unable or do not want to inject, or who primarily snort opioids. Early experimental data has demonstrated that intranasal DAM administration can be a viable alternative to the intravenous or intramuscular route of administration. The purpose of this study is to assess the feasibility, safety, and acceptability of intranasal HAT.. This study will assess intranasal DAM using a prospective multicentre observational cohort study design in HAT clinics across Switzerland. Patients will be offered to switch from oral or injectable DAM to intranasal DAM. Participants will be followed-up over 3 years, with assessments at baseline, and after 4, 52, 104 and 156 weeks. The primary outcome measure (POM) is retention in treatment. Secondary outcomes (SOM) include prescriptions and routes of administration of other opioid agonists, illicit substance use, risk behaviour, delinquency, health and social functioning, treatment adherence, opioid craving, satisfaction, subjective effects, quality of life, physical health, and mental health.. The results derived from this study will generate the first major body of clinical evidence on the safety, acceptability, and feasibility of intranasal HAT. If proven to be safe, feasible and acceptable, this study would increase the accessibility of intranasal OAT for individuals with OUD globally as a critical improvement in risk reduction.

Topics: Analgesics, Opioid; Feasibility Studies; Heroin; Humans; Multicenter Studies as Topic; Observational Studies as Topic; Opioid-Related Disorders; Prospective Studies; Quality of Life; Switzerland

Recovery from opioid use disorder (OUD) and maintenance of abstinence from opioid use is hampered by perseverant drug cravings that may persist for months after cessation of drug use. Drug cravings can intensify during the abstinence period, a phenomenon referred to as the 'incubation of craving' that has been well-described in preclinical studies. We previously reported that animals that self-administered heroin at a dosage of 0.075 mg/kg/infusion (HH) paired with discrete drug cues displayed robust incubation of heroin craving behavior after 21 days (D) of forced abstinence, an effect that was not observed with a lower dosage (0.03 mg/kg/infusion; HL). Here, we sought to elucidate molecular mechanisms underlying long-term heroin seeking behavior by profiling microRNA (miRNA) pathways in the orbitofrontal cortex (OFC), a brain region that modulates incubation of heroin seeking. miRNAs are small noncoding RNAs with long half-lives that have emerged as critical regulators of drug seeking behavior but their expression in the OFC has not been examined in any drug exposure paradigm. We employed next generation sequencing to detect OFC miRNAs differentially expressed after 21D of forced abstinence between HH and HL animals, and proteomics analysis to elucidate miRNA-dependent translational neuroadaptations. We identified 55 OFC miRNAs associated with incubation of heroin craving, including miR-485-5p, which was significantly downregulated following 21D forced abstinence in HH but not HL animals. We bidirectionally manipulated miR-485-5p in the OFC to demonstrate that miR-485-5p can regulate long-lasting heroin seeking behavior after extended forced abstinence. Proteomics analysis identified 45 proteins selectively regulated in the OFC of HH but not HL animals that underwent 21D forced abstinence, of which 7 were putative miR-485-5p target genes. Thus, the miR-485-5p pathway is dysregulated in animals with a phenotype of persistent heroin craving behavior and OFC miR-485-5p pathways may function to support long-lasting heroin seeking.

Topics: Animals; Craving; Cues; Drug-Seeking Behavior; Heroin; Male; MicroRNAs; Opioid-Related Disorders; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Self Administration

Although opioids are necessary for the treatment of acute pain, cancer pain, and palliative care, opioid abuse is a serious threat to society. Heroin (Diacetylmorphine) is the most commonly abused opioid, and it can have a variety of effects on the body's tissues and organs, including the well-known gastrointestinal depression and respiratory depression; however, there is little known about the effects of diacetylmorphine on cardiac damage. Here, we demonstrate that diacetylmorphine induces abnormal electrocardiographic changes in rats and causes damage to cardiomyocytes in vitro by an underlying mechanism of increased autophosphorylation of CaMKII and concomitant regulation of myocardial contractile protein TPM1 and MYOM2 protein expression. The CaMKII inhibitor KN-93 was first tested to rescue the toxic effects of heroin on cardiomyocytes in vitro and the abnormal ECG changes caused by heroin in SD rats, followed by the TMT relative quantitative protein technique to analyze the proteome changes. Diacetylmorphine causes increased phosphorylation at the CaMKII Thr287 site in myocardium, resulting in increased autophosphorylation of CaMKII and subsequent alterations in myocardial contractile proteins, leading to myocardial rhythm abnormalities. These findings provide a theoretical basis for the treatment and prevention of patients with arrhythmias caused by diacetylmorphine inhalation and injection.

Topics: Analgesics, Opioid; Animals; Arrhythmias, Cardiac; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Heroin; Myocytes, Cardiac; Opioid-Related Disorders; Phosphorylation; Rats; Rats, Sprague-Dawley; Tropomyosin

In 2020, drug related deaths in the United Kingdom (UK) reached the highest rate in over 25 years, with hospitalisations and deaths particularly impacting people who use illicit opioids such as heroin. Treatment systems are increasingly required to be innovative to engage the most vulnerable at risk from premature morbidity and mortality. Heroin Assisted Treatment (HAT) is an alternative treatment modality for people for whom more traditional forms of opioid substitution therapy, such as methadone, have been ineffective. Middlesbrough, a town in the North-East England, was home to the first service in the UK to implement HAT outside of a clinical trial setting which closed for operation in November 2022.. Qualitative in-depth interviews with patients and health care providers (n =17) involved in the delivery of HAT were undertaken during 2021. This paper focuses on the health care provider interviews, the majority of which took place remotely. Interviews were audio recorded and thematically analysed.. Health care providers navigated multiple layers of constraint during HAT implementation and delivery. We explore this in relation to three themes: 1) Negotiating risk and safety within treatment 2) More than a prescription: care beyond diamorphine 3) Internal and external delivery barriers and impact on treatment acceptability, identity and longevity. Negotiating and managing risks of polysubstance use was a complex task. Benefits regarding access to holistic care, improved therapeutic and social relationships were recognised by practitioners. The rigorous delivery schedule was the biggest barrier to engagement. Outside the treatment room, socio-structural factors posed additional challenges.. Despite some operational complexities, health care providers viewed HAT as an effective method of engaging a high risk population with drug treatment services, with holistic benefits for clients over and above the treatment of opioid dependency. Findings will inform advocacy and innovation for future HAT interventions in England.

Topics: Analgesics, Opioid; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Qualitative Research

Treatment for opioid use disorder (OUD) with diacetylmorphine is an evidence-based form of drug treatment, but it is not available in the United States (US). Better understanding acceptability of treatment with injectable diacetylmorphine among people who use opioids (PWUO) in the US may expedite future initiatives designed to engage persons in this form of treatment should it become available. The purpose of this research is to examine factors associated with interest in treatment with injectable diacetylmorphine among a sample of PWUO in the US.. Data are from a cross-sectional study of PWUO in Baltimore City, Maryland. Participants were given a brief description of treatment with injectable diacetylmorphine and then asked to rate their level of interest. We used Poisson regression with robust variance to assess factors associated with interest in treatment with injectable diacetylmorphine.. The average age of participants was 48 years, 41% were women, and most (76%) identified as non-Hispanic, Black. The most commonly used substances were non-injection heroin (76%), opioid pain relievers (73%), and non-injection crack/cocaine (73%). Two-thirds of participants (68%) indicated interest in treatment with injectable diacetylmorphine. Factors significantly associated with interest in injectable diacetylmorphine treatment included: having at least a high school education (adjusted prevalence ratio [aPR]: 1.23; 95% confidence interval [CI]: 1.04-1.45), not having health insurance (aPR: 1.23; 95% CI: 1.06-1.44), having ever overdosed (aPR: 1.20; 95% CI: 1.01-1.42), and past utilization of medications for opioid use disorder (aPR: 1.22; 95% CI: 1.01-1.47). Recent non-injection cocaine use was inversely associated with interest in treatment with injectable diacetylmorphine (aPR 0.80; 95% CI: 0.68-0.94).. The majority of participants reported interest in treatment with injectable diacetylmorphine. Given worsening trends in the addiction and overdose crisis in the US, treatment with injectable diacetylmorphine should be considered as another evidence-based option for treating OUD.KEY MESSAGESInterest in treatment with injectable diacetylmorphine was high among a sample of people who use opioids in the United States.Factors associated with increased interest in treatment with injectable diacetylmorphine included having at least a high school education, having ever overdosed, and not having health insurance.Past utilization of medications for opioid use disorder was associated with interest in treatment with injectable diacetylmorphine.

Topics: Analgesics, Opioid; Baltimore; Cocaine; Cross-Sectional Studies; Drug Overdose; Female; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; United States

Patients in methadone medication treatment for opioid use disorder (M-MOUD) typically have a complex history of opioid use, often in combination with other drugs. It is unknown how frequently M-MOUD patients experience persistent substance or polysubstance use. We measured trends in illicit substance use in a large, multistate population of M-MOUD patients and persistence of substance use in the first year of treatment.. Retrospective cohort study of United States (US) M-MOUD patients from 2017 to 2021, focused on urine drug specimens provided for testing to Millennium Health, a third-party laboratory. Specimens were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Generalized estimating equations (GEE) were used to estimate the average trends in positivity during time in treatment.. Specimens were obtained from clinics in 10 US states that provided at least 300 unique patients during the study period (Alaska, Arizona, Florida, Illinois, Kentucky, Minnesota, New Mexico, Ohio, Virginia and Washington).. Patients with opioid use disorder receiving M-MOUD (n = 16 386).. Positivity rates for heroin, fentanyl, methamphetamine and cocaine.. From 2017 to 2021, yearly crude positivity rates for first collected specimens increased for fentanyl (13.1%-53.0%, P < 0.001), methamphetamine (10.6%-27.2%, P < 0.001) and cocaine (13.8%-19.5%, P < 0.001); for heroin positivity did not significantly change (6.9%-6.5%, P = 0.74). In regression models estimating patient trajectories from week 1 to week 52, marginal fentanyl positivity declined from 21.8% to 17.1% (incidence rate ratio [IRR] = 0.78, P < 0.001) and heroin positivity declined from 8.4% to 4.3% (IRR = 0.51, P < 0.001), but positivity for methamphetamine and cocaine did not significantly change, remaining at an average of 17.7% (IRR = 0.98, P = 0.53) and 9.2% (IRR = 0.96, P = 0.36), respectively.. Between 2017 and 2021, United States patients presenting to opioid treatment programs increasingly tested positive for fentanyl, methamphetamine and cocaine. Methadone medication treatment for opioid use disorder appears to remain an effective intervention for reducing illicit opioid use.

Topics: Analgesics, Opioid; Chromatography, Liquid; Cocaine; Fentanyl; Heroin; Humans; Methadone; Methamphetamine; Opioid-Related Disorders; Patient Safety; Retrospective Studies; Tandem Mass Spectrometry; United States

Medications for opioid use disorder (MOUD; methadone, buprenorphine, naltrexone) are the most effective treatments for OUD, and MOUD is protective against fatal overdoses. However, continued illegal drug use can increase the risk of treatment discontinuation. Given the widespread presence of fentanyl in the drug supply, research is needed to understand who is at greatest risk for concurrent MOUD and drug use and the contexts shaping use and treatment discontinuation.. From 2017 to 2020, Massachusetts residents with past-30-day illegal drug use completed surveys (N = 284) and interviews (N = 99) about MOUD and drug use. An age-adjusted multinomial logistic regression model tested associations between past-30-day drug use and MOUD use (current/past/never). Among those on methadone or buprenorphine (N = 108), multivariable logistic regression models examined the association between socio-demographics, MOUD type; and past-30-day use of heroin/fentanyl; crack; benzodiazepines; and pain medications. Qualitative interviews explored drivers of concurrent drug and MOUD use.. Most (79.9%) participants had used MOUD (38.7% currently; 41.2% past), and past 30-day drug use was high: 74.4% heroin/fentanyl; 51.4% crack cocaine; 31.3% benzodiazepines, and 18% pain medications. In exploring drug use by MOUD history, multinomial regression analyses found that crack use was positively associated with past and current MOUD use (outcome referent: never used MOUD); whereas benzodiazepine use was not associated with past MOUD use but was positively associated with current use. Conversely, pain medication use was associated with reduced odds of past and current MOUD use. Among those on methadone or buprenorphine, separate multivariable logistic regression models found that benzodiazepine and methadone use were positively associated with heroin/fentanyl use; living in a medium-sized city and sex work were positively associated with crack use; heroin/fentanyl use was positively associated with benzodiazepine use; and witnessing an overdose was inversely associated with pain medication use. Many participants qualitatively reported reducing illegal opioid use while on MOUD, yet inadequate dosage, trauma, psychological cravings, and environmental triggers drove their continued drug use, which increased their risk of treatment discontinuation and overdose.. Findings highlight variations in continued drug use by MOUD use history, reasons for concurrent use, and implications for MOUD treatment delivery and continuity.

Topics: Analgesics, Opioid; Benzodiazepines; Buprenorphine; Crack Cocaine; Drug Overdose; Fentanyl; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pharmaceutical Preparations

Although opioid misuse has been decreasing among US youths and adolescents in recent years, it is unclear what has contributed to this trend and how this trend differs by age group and sex over time.. To identify trends in opioid misuse among youths and young adults across and between ages, birth cohorts, and sexes.. Cross-sectional National Survey on Drug Use and Health (NSDUH) public-use files were used to produce nationally representative pseudocohorts. The survey population includes the civilian US population in the 50 states and Washington, DC. Individuals without a fixed address and institutionalized individuals were excluded. Respondents to the NSDUH are a population-based sample selected using a stratified cluster design. For the years (January 1, 2002, to December 31, 2019) and ages (12-21 years) analyzed, the sample sizes ranged from 1607 to 3239 respondents. Data were analyzed from January 1, 2022, to April 12, 2023, for the main outcome by age, sex, and pseudocohort.. Respondents were asked whether they misused prescription opioids or used heroin in the past year. The analysis hypotheses were formulated and tested after data collection.. In a total of 5 pseudocohorts, data from 114 412 respondents aged 12 to 21 years were analyzed; the unweighted distribution of male sex (complement was female) ranged from 47.7% to 52.6% (mean [SD], 50.6% [1.1%]). Response rates ranged from 45.8% to 71.3%. High school-aged youths and young adults had distinctly lower rates of opioid misuse in later pseudocohorts compared with earlier ones. Rates of misuse among individuals aged 16 years were 2.80% (95% CI, 1.06%-4.54%) higher in 2002 vs 2008; among those aged 18 years, rates were 4.36% (95% CI, 1.85%-6.87%) higher in 2002. Similarly, rates of misuse among individuals aged 16 years were 3.93% (95% CI, 2.15%-5.71%) higher in 2008 vs 2014; among those aged 17 years, rates were 3.41% (95% CI, 1.94%-4.88%) higher in 2008. Similar patterns were observed by sex. In earlier cohorts, younger female participants had higher rates of opioid misuse than their male counterparts and older male participants had higher rates than their female counterparts. Sex differences decreased in later cohorts.. The findings of this cross-sectional study of US youths and young adults suggest that high school-aged individuals consistently misused fewer opioids in later pseudocohorts overall and by sex. Sex differences in opioid rates also diminished in later pseudocohorts. A decrease in drug availability and general exposure to the harms of opioid use could be contributing to these findings. Future planned research using this pseudocohort approach will examine polysubstance use and evaluate how substance use differs by other sociodemographic characteristics.

Topics: Adolescent; Analgesics, Opioid; Child; Cross-Sectional Studies; Female; Heroin; Humans; Male; Opioid-Related Disorders; Prescription Drug Misuse; Young Adult

Opioid use disorder (OUD) looms as one of the most severe medical crises facing society. More effective therapeutics will require a deeper understanding of molecular changes supporting drug-taking and relapse. Here, we develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability. Comparisons with human OUD RNA-seq and genome-wide association study data revealed convergent molecular abnormalities and gene candidates with high therapeutic potential. These studies outline molecular reprogramming underlying OUD and provide a foundational resource for future investigations into mechanisms and treatment strategies.

Topics: Animals; Brain; Genome-Wide Association Study; Heroin; Humans; Male; Mice; Opioid-Related Disorders; Recurrence; Reward

Heroin-assisted treatment (HAT) involves supervised dispensing of medical heroin (diacetylmorphine) for people with opioid use disorder. Clinical evidence has demonstrated the effectiveness of HAT, but little is known about the self-reported satisfaction among the patients who receive this treatment. This study presents the first empirical findings about the patients' experiences of, and satisfaction with, HAT in the Norwegian context.. Qualitative in-depth interviews with 26 patients in HAT were carried out one to two months after their enrollment. Analysis sought to identify the main benefits and challenges that the research participants experienced with this treatment. An inductive thematic analysis was conducted to identify the main areas of benefits and challenges. The benefits were weighed against the challenges in order to assess the participants' overall level of treatment satisfaction.. Analysis identified three different areas of experienced benefits and three areas of challenges of being in this treatment. It outlines how the participants' everyday lives are impacted by being in the treatment and how this, respectively, results from the treatment's medical, relational, or configurational dimensions. We found an overall high level of treatment satisfaction among the participants. The identification of experienced challenges reveals factors that reduce satisfaction and thus may hinder treatment retention and positive treatment outcomes.. The study demonstrates a novel approach to qualitatively investigate patients' treatment satisfaction across different treatment dimensions. The findings have implications for clinical practice by pointing out key factors that inhibit and facilitate patients' satisfaction with HAT. The identified importance of the socio-environmental factors and relational aspect of the treatment has further implications for the provision of opioid agonist treatment in general.

Topics: Heroin; Humans; Opioid-Related Disorders; Patient Satisfaction; Qualitative Research; Self Report

Rates of illicit opioid use are particularly high among young adults, yet research on overdose experience and factors associated with overdose in this population remains limited. This study examines the experiences and correlates of non-fatal overdose among young adults using illicit opioids in New York City (NYC).. 539 participants were recruited via Respondent-Driven Sampling in 2014-2016. Eligibility criteria included: aged 18-29 years old; current residence in NYC; and nonmedical prescription opioid (PO) use and/or heroin use in the past 30 days. Participants completed structured interviews to assess their socio-demographics, drug use trajectories, current substance use and lifetime and most recent overdose experiences, and were tested on-site for hepatitis C virus (HCV) antibodies.. 43.9% of participants reported lifetime overdose experience; of these, 58.8% had experienced two or more overdose events. The majority of participants' most recent overdoses (63.5%) were due to polysubstance use. In bivariable analyses, after RDS adjustment, having ever overdosed was correlated with: household income of >$100,00 growing up (vs. $51,000-100,000); lifetime homelessness; HCV antibody-positive status; lifetime engagement in regular nonmedical benzodiazepine use, regular heroin injection and regular PO injection; and using a non-sterile syringe in the past 12 months. Multivariable logistic regression identified childhood household income >$100,00 (AOR=1.88), HCV-positive status (AOR=2.64), benzodiazepine use (AOR=2.15), PO injection (AOR=1.96) and non-sterile syringe use (AOR=1.70) as significant independent correlates of lifetime overdose. A multivariable model with multiple overdoses (vs. one) found only lifetime regular heroin use and PO injection to be strong correlates.. Results indicate a high prevalence of lifetime and repeated overdose among opioid-using young adults in NYC, highlighting a need for intensified overdose prevention efforts for this population. The strong associations of HCV and indices of polydrug use with overdose suggest that prevention efforts should address the complex risk environment in which overdose occurs, attending to the overlapping nature of disease-related risk behavior and overdose risk behavior among young people who inject opioids. Overdose prevention efforts tailored for this group may find it useful to adopt a syndemic conception of overdose that understands such events as resulting from multiple, and often interrelated, risk factors.

Topics: Adolescent; Adult; Analgesics, Opioid; Benzodiazepines; Child; Hepatitis C; Heroin; Humans; New York City; Opioid-Related Disorders; Syndemic; Young Adult

Opioid-involved deaths are continuing to increase across the United States, exceeding 100,000 for the first time in 2021. Contamination with, and intentional use of, synthetic opioids such as fentanyl are a major driver of this increase. Utilizing self-report substance use data of patients being treated in the emergency department (ED) can be useful to determine which substances patients are intentionally seeking.. 1) Examine changes in self-reported illicit substance use (including fentanyl) over time; 2) Examine changes in the co-occurrence of self-reported fentanyl with other illicit substance use over time.. All patients presenting to the study EDs that answered anything other than "never" on the National Institute on Drug Abuse Quick Screen and were seen by a peer recovery specialist in the ED between July 1, 2020 and December 31, 2022 were included for analysis. The substance of use as reported by each patient was recorded by the peer recovery specialist. Differences in substance use by type over time were examined using chi-squared tests of proportions.. There were 7568 patients that met inclusion criteria. Self-reported fentanyl (1760%; p < 0.0001) and cocaine (82%; p = 0.034) use increased, whereas heroin use (16%; p < 0.0001) decreased.. Self-reported fentanyl and cocaine use has increased significantly in South Carolina ED patients between 2020 and 2022. Given the high morbidity and mortality associated with fentanyl and fentanyl analog use, further measures to identify these patients and provide harm reduction and treatment from the ED setting are warranted.

Topics: Analgesics, Opioid; Cocaine; Drug Overdose; Emergency Service, Hospital; Fentanyl; Heroin; Humans; Opioid-Related Disorders; Self Report; South Carolina; United States

Co-occurring heroin and methamphetamine use is a growing public health problem. This study assessed the characteristics of Medicaid patients admitted to substance use disorder (SUD) treatment programs for heroin and methamphetamine use compared with patients admitted for heroin only.. The study identified patients who entered treatment for heroin and methamphetamine and those admitted for heroin only between 2014 and 2017 from the Oregon Treatment Episode Data Set linked with Medicaid enrollment, and medical and pharmacy claims. We used a cross-sectional design to compare demographics, type of treatment, and substance use characteristics between the two groups. We used logistic regression models to assess differences in the odds of opioid-related and all-cause adverse events.. Among the 3802 study sample, 2004 (53%) were admitted for both heroin and methamphetamine use. The heroin and methamphetamine group were more likely to be younger, female, White or American Indian/Alaska Native; and had more comorbidities than patients admitted for heroin only. Patients admitted for heroin and methamphetamine treatment were less likely to receive any medication for opioid use disorder (MOUD) (56% vs 75%, p < 0.001) and received fewer days of MOUD treatment (mean 188 vs. 265 days, p < 0.001) compared to the heroin only group. The heroin and methamphetamine group were more likely to receive buprenorphine (28.1% vs 24.2%) and less likely to receive methadone (39.9% vs 62.5%). The heroin and methamphetamine group began use at a younger age, used and injected more frequently than those admitted for heroin only. Patients treated for heroin and methamphetamine had 17% lower odds of OUD-related adverse events (aOR 0.83; 95% CI 0.70-0.99) and 52% higher odds of all-cause adverse events (aOR 1.52; 95% CI 1.14-2.03) relative to the heroin only group.. Patients admitted for both heroin and methamphetamine reported greater addiction severity (more frequent use, earlier onset of use, and injection use), yet less commonly received MOUD compared to those who were admitted for heroin only. These findings indicate substantial missed opportunities for MOUD treatment even among people who successfully engage with the SUD treatment system.

Topics: Cross-Sectional Studies; Delivery of Health Care; Female; Heroin; Humans; Methamphetamine; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Whether expanded access to naloxone reduces perceptions of risk about opioid use has been subject to debate. Our aim was to assess how implementation of naloxone access laws shapes perceived risk of heroin use.. Using data from the restricted-access National Survey on Drug Use and Health, Prescription Drug Abuse Policy System and the US Census, we applied two-way fixed-effects models to determine whether naloxone access laws decreased perceived risk of any heroin use or regular heroin use. We used Bayes factors (BFs) to confirm evidence for null findings.. United States.. A total of 884 800 respondents aged 12 and older from 2004 to 2016.. A binary indicator of whether a state implemented naloxone access laws was regressed on respondent-perceived risk of (1) any heroin use and (2) regular heroin use. Ratings of perceived risk were assessed on a scale of 1 (none) to 4 (great risk).. In all instances, the BFs support evidence for the null hypothesis. Across models with three distinct specifications of naloxone access laws, we found no evidence of decreased risk perceptions, as confirmed by BFs ranging from 0.009 to 0.057. Across models of specific vulnerable subgroups, such as people who use opioids (BFs = 0.039-0.225) or young people (BFs = 0.009-0.158), we found no evidence of decreased risk perceptions. Across diverse subpopulations by gender (BFs = 0.011-0.083), socio-economic status (BFs = 0.015-0.168) or race/ethnicity (BFs = 0.016-0.094), we found no evidence of decreased risk perceptions.. There appears to be no empirical evidence that implementation of naloxone access laws has adversely affected perceptions of risk of heroin in the broader US population or within vulnerable subgroups or diverse subpopulations.

Topics: Adolescent; Analgesics, Opioid; Bayes Theorem; Drug Overdose; Heroin; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; United States

Opioid agonist treatment (OAT) is an effective intervention for opioid dependence. Extended-release buprenorphine injections (BUP-XR) may have additional potential benefits over sublingual buprenorphine. This single-arm trial evaluated outcomes among people receiving 48 weeks of BUP-XR in diverse community healthcare settings in Australia, permitting examination of outcomes when BUP-XR is delivered in standard practice.. Participants were recruited from a network of specialist public drug treatment services, primary care and some private practices in three states. Following a minimum 7 days on 8-32 mg of sublingual buprenorphine (±naloxone), participants received monthly subcutaneous BUP-XR injections administered by a healthcare practitioner and completed monthly research interviews. The primary endpoint was retention in treatment at 48 weeks.. Participants (n = 100) were 28% women, mean age 44 years with a long history of OAT (median 5.8 years); heroin was the most common opioid of concern (58%). Treatment retention at 24 and 48 weeks was 86% and 75%, respectively. Participants with past-month injecting drug use (OR 0.23; 95%CI: 0.09-0.61) or heroin use (OR 0.23; 95%CI: 0.08-0.65) at baseline had lower odds of being retained in treatment to 48 weeks. Reductions in multiple forms of extra-medical drug use were observed. Improvements in quality of life, participation in employment, and treatment satisfaction measures were also observed.. This real-world implementation study of BUP-XR demonstrated high retention and treatment satisfaction. This study provides important additional data on the uptake and experience of clients, with relevance for policy makers, health service planners, administrators, and practitioners.. Indivior.. ClinicalTrials.gov Identifier: NCT03809143.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Heroin; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Quality of Life

The authors examined directly whether county-level changes in opioid dispensing rates affect individual-level prescription opioid misuse, frequency of use, and dependence, as well as the same outcomes for heroin.. Using data from the restricted-access National Survey on Drug Use and Health, the Centers for Disease Control and Prevention's retail opioid prescription database, the Prescription Drug Abuse Policy System, and the U.S. Census, the authors applied fixed-effects models to determine whether county-level dispensing rates affected prescription opioid outcomes as intended and whether changes in rates adversely affected heroin use outcomes. Bayes factors were used to confirm evidence for null findings.. The sample included 748,800 respondents age 12 and older from 2006 to 2016. The odds of prescription opioid misuse, increased frequency of misuse, and dependence were 7.2%, 3.5%, and 10.4% higher, respectively, per standard deviation increase in the county-level opioid dispensing rate per 100 persons. There was no evidence for any association between opioid dispensing rates and the three heroin outcomes. The odds ratio was nonsignificant according to frequentist techniques in fixed-effects models, and Bayesian techniques confirmed very strong support for the null hypothesis.. County-level opioid dispensing rates are directly associated with individual-level prescription opioid misuse, frequency of misuse, and dependence. Changes in dispensing were not associated with population shifts in heroin use. Reductions in opioid dispensing rates have contributed to stemming prior increases in prescription opioid misuse while not adversely affecting heroin use. Physicians and other health care providers can take action to minimize opioid dispensing for tangible benefits regarding prescription opioid misuse without adverse effects on heroin use.

Topics: Analgesics, Opioid; Bayes Theorem; Child; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Prescriptions; United States

The opioid crisis has devastated the U.S. more than any other country, and the epidemic is getting worse. While opioid prescriptions have decreased by more than 40% from its peak in 2010, unfortunately, opioid-related overdose deaths have not declined but continued to increase. With greater scrutiny on prescription opioids, many users switched to the cheaper and more readily available heroin that drove up heroin-related overdose deaths from 2010 to peak in 2016, being overtaken by the spike in synthetic opioid (mostly fentanyl)-related overdose deaths. The surge in fentanyl-related overdose deaths since 2013 is alarming as fentanyl is more potent and deadly. One thing is certain the opioid crisis is not improving but has become dire with the surge in fentanyl-related overdose deaths. Evidence-based strategies have to be implemented in the U.S. to control this epidemic before it destroys more lives. Other countries, including European countries and Canada, have invested more in harm reduction strategies than the U.S. even though they (especially Europe) do not face anywhere near the level of crisis as the U.S. In the long-run, upstream measures (tackling the social determinants of health) are more effective public health strategies to control the epidemic. In the meantime, however, harm reduction strategies have to be employed to mitigate the harm from addiction and overdose deaths.

Topics: Analgesics, Opioid; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Fentanyl; Harm Reduction; Heroin; Humans; Hypnotics and Sedatives; Opioid Epidemic; Opioid-Related Disorders; Public Health; United States

Heroin-assisted treatment comprises the use of diacetylmorphine (pharmaceutical heroin) for individuals with severe opioid use disorder. In Switzerland, take-home doses in heroin-assisted treatment are more strictly regulated as compared to conventional opioid agonist treatment. In light of the COVID-19 pandemic, the Swiss Federal Council provisionally adapted its policy, allowing for longer prescriptions of take-home diacetylmorphine. Before the beginning of the pandemic, take-home doses only occurred in exceptional circumstances and under strict criteria for patient eligibility. Following the legislative adaptations, we critically revised our internal centre policies as well. We report our experiences with oral take-home diacetylmorphine from a Swiss outpatient university centre specialising in heroin-assisted treatment. An additional 45 patients received take-home doses following the first lockdown. While some patients wished to return to their previous treatment regimen, most patients managed their medication well and showed good adherence. We also noticed an increase of treatment admissions that are likely related to the relaxed regulations. Previously, the strict therapeutic framework of visiting a HAT centre twice a day for supervised dispensing seemed to have discouraged these individuals from seeking medical treatment. From a medical point of view, the politically driven restrictions on take-home doses in heroin-assisted treatment are questionable and do not support the goal of harm reduction.

Topics: Analgesics, Opioid; Communicable Disease Control; COVID-19; Heroin; Humans; Opioid-Related Disorders; Pandemics; SARS-CoV-2; Switzerland

One objective of the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative is to accelerate research on safer and more effective medications for both pain and opioid use disorder. Ligands that activate the nociceptin opioid peptide receptor (NOP) constitute one class of candidate drugs for both applications. The present preclinical study determined the effectiveness of the NOP agonist Ro 64-6198 to produce antinociception in a pain-depressed behavior procedure and attenuate opioid self-administration in a heroin-vs-food choice procedure.. In Experiment 1, Adult Sprague-Dawley rats were equipped with microelectrodes and trained to respond for electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. The potency, time course, and receptor mechanism of effects produced by R0 64-6198 alone (0.32-3.2 mg/kg) on ICSS were examined, followed by evaluation of 0.32-1.0 mg/kg Ro 64-6198 effectiveness to block lactic acid-induced depression of ICSS. In Experiment 2, rats self-administered heroin under a heroin-vs-food choice procedure during a regimen of repeated, daily intraperitoneal administration of vehicle or Ro 64-6198 (1-3.2 mg/kg/day).. Ro 64-6198 produced dose- and time-dependent ICSS depression that was blocked by the selective NOP antagonist SB612111 but not by naltrexone. Ro 64-6198 failed to block acid-induced depression of ICSS. Repeated Ro 64-6198 pretreatment also failed to attenuate heroin-vs-food choice up to doses that significantly decreased operant behavior.. These results do not support the utility of Ro 64-6198 as a stand-alone medication for either acute pain or opioid use disorder.

Topics: Acute Pain; Animals; Dose-Response Relationship, Drug; Heroin; Imidazoles; Nociceptin; Opioid Peptides; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Spiro Compounds

Topics: Adult; Buprenorphine; Contraception; Drug Overdose; Female; Harm Reduction; Heroin; Humans; Male; Methadone; Methamphetamine; Naloxone; Opioid-Related Disorders; Pregnancy; Quality of Life; Referral and Consultation; Substance-Related Disorders

Topics: Animals; Heroin; Male; Mice; Mice, Inbred ICR; Morphine Dependence; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Secologanin Tryptamine Alkaloids; Substance Withdrawal Syndrome

The prevalence of opioid use disorder during pregnancy is increasing in the United States. However, evidence to guide appropriate dosing of pharmacotherapy for the treatment of opioid use disorder, such as methadone, based on self-reported opioid use during pregnancy is limited.. This study aimed to examine the relationship between self-reported consumption of heroin and methadone dose among pregnant people with opioid use disorder admitted to the hospital for methadone titration.. This was an analysis of a single-site retrospective cohort of pregnant people admitted for the management of opioid use disorder at an urban, tertiary care center between 2013 and 2020. Patient-reported consumption of heroin was evaluated by clinical staff and described as a self-reported dollar amount of heroin consumed per day. The primary outcome was methadone dose at the time of discharge. The secondary outcome was methadone dose at the time of delivery. Bivariate and linear regression modeling were performed. A priori covariates included in the model were an epoch of admission, Clinical Opioid Withdrawal Scale score at the time of admission, gestational age at admission, and need for readmission because of recurrent opioid use. A sensitivity analysis was performed using propensity score matching. Statistical significance was set at P<.05.. Of 100 people admitted during the study period, 53 and 47 individuals met the inclusion criteria for the primary and secondary outcomes, respectively. On bivariate and multivariate linear regression modeling, the self-reported dollar amount of heroin consumed per day was independently associated with the dose of methadone at the time of discharge. For every $10 of heroin consumed, the dosage of methadone increased by 1.3 mg (95% confidence interval, 0.4-2.2). On sensitivity analysis with the use of a propensity score, the self-reported dollar amount of heroin consumed per day was independently associated with the dose of methadone at the time of discharge. There was no significant relationship between self-reported dollar amount of heroin consumed per day and methadone dose at the time of delivery.. Self-reported dollar amount of heroin consumed per day was independently associated with the dose of methadone at the time of discharge, but not at the time of delivery. These data can be useful in clinical counseling and management of pregnant people with opioid use disorder admitted for initiation of methadone.

Topics: Analgesics, Opioid; Female; Heroin; Humans; Methadone; Opioid-Related Disorders; Pregnancy; Retrospective Studies; Self Report

The current phase of the North American 'opioid crisis' is characterised by illicit fentanyl use; however, the presence of illicit fentanyl in Australia is unknown. This study aimed to monitor unintentional fentanyl consumption in Australia.. Rapid urine drug screens (UDS) paired with surveys conducted within supervised injecting facilities (SIFs) and confirmatory laboratory testing.. Sydney and Melbourne, Australia.. Clients who used heroin within the past 2 days (n = 911 tests, 2017-2021). Participants were demographically similar to the overall client base (median age 43, 72% male).. UDS were conducted using BTNX Rapid Response fentanyl urine strip tests with cross-reactivity to numerous fentanyl analogues. Positive urine samples were analysed using liquid chromatography coupled with tandem mass spectrometry. Surveys covered past 3 day drug use and lifetime report of fentanyl in heroin.. Two percent of participants reported intentional use of fentanyl, mostly through fentanyl patches. Of the 911 rapid UDS conducted, 17 (1.9%) yielded positive results. Eight of these (all from Melbourne) were not explained by survey-reported fentanyl use in the past 3 days. Of these 8 unexplained positives, confirmatory laboratory analysis was conducted on 6, with 4 deemed to be false positives, and 2 confirmed for the presence of fentanyl. This represents the first confirmation of unintended use of fentanyl type substances in this population.. There is limited evidence of unintentional fentanyl use among people in Sydney and Melbourne, Australia who regularly inject heroin, suggesting that, currently, there is very little illicit fentanyl in Australian drug markets accessed by supervised injecting facilities attendees. This study demonstrates the feasibility of quick onsite testing to cost-effectively screen large samples for fentanyl; however, the high false positive rate emphasises the need for confirmation of positive tests through advanced analytical techniques.

Topics: Adult; Analgesics, Opioid; Australia; Drug Overdose; Female; Fentanyl; Heroin; Humans; Male; Opioid-Related Disorders; Urinalysis

Extended-release injectable naltrexone (XR-naltrexone) is effective for treatment of patients with opioid use disorder (OUD), but initiation remains a barrier due to the challenge of tolerating opioid withdrawal prior to administration. Understanding factors associated with successful initiation of XR-naltrexone could facilitate its implementation through patient-treatment matching.. We combined data from five consecutive studies that sought to initiate patients with active opioid use onto XR-naltrexone using a rapid procedure consisting of minimal buprenorphine, non-opioid medications for treating opioid withdrawal, and ascending low doses of oral naltrexone. Associations between patient characteristics and initiating naltrexone were estimated with logistic regression models. To evaluate whether associations differed between inpatient and outpatient settings, patient characteristic-by-setting interactions were also estimated.. 409 patients were included in the analyses and 228 (56%) received the first injection. A significantly greater percent of inpatients (62%) vs outpatients (48%) initiated XR-naltrexone. Initiation success was significantly more likely on an inpatient basis for heroin (60.9% inpatient vs 36.2% outpatient), intravenous (56.3% inpatient vs 22.5% outpatient), and speedball users (68.1% inpatient vs 32.3% outpatient). Prescription opioid users showed similar, higher initiation rates across settings (68.9% inpatient; 73.7% outpatient).. An inpatient setting may be the preferred strategy for rapid initiation of XR-naltrexone for opioid users with greater severity, including heroin or speedball injection users or those who use opioids intravenously. Initiation on an outpatient basis may be more likely to succeed for prescription opioid users.

Topics: Analgesics, Opioid; Delayed-Action Preparations; Heroin; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

There is a lack of safe and effective non-opioid medications for the treatment of opioid addiction. Aquaporin-4 (AQP4), a water channel protein expressed in astrocytes, regulates the progression of neurological diseases. Our previous work demonstrated that AQP4 deficiency in mice attenuated morphine-induced physiological dependence. However, the role of AQP4 in the neurobiology of behaviours related to opioid addiction in mice remains unclear. Here, we report that Aqp4-knockout mice exhibited attenuated heroin consumption and heroin-seeking behaviours. Furthermore, Aqp4-knockout mice displayed diminished hyperactivity induced by morphine and heroin and subsequently showed dramatically inhibited morphine-induced behavioural sensitization. This attenuated hyperlocomotion to opioids was accompanied by a decreased dopamine response to the opioid-induced increase in the levels of extracellular dopamine in the NAc. In addition, Aqp4-knockout mice displayed upregulation of dopamine transporters in the striatum, suggesting a probable neurobiological mechanism for uptake of the extracellular dopamine. The present findings suggest that deficiency of AQP4 decreases opiate-induced drug seeking and taking behaviours, and AQP4 may be involved in the treatment of addiction. Therefore, the development of a pharmacological antagonist to AQP4 may be valuable to investigate as opioid addiction therapy.

Topics: Analgesics, Opioid; Animals; Aquaporin 4; Behavior, Addictive; Dopamine; Heroin; Mice; Mice, Knockout; Morphine; Morphine Dependence; Nucleus Accumbens; Opioid-Related Disorders

Opioid use disorder continues to have a significant impact on public health morbidity and mortality throughout the United States and elsewhere. Managing opioid withdrawal is a critical treatment goal in individuals entering treatment with an active opioid use.. What are the milestones of the changes in the expert approach to the pharmacological management of heroin withdrawal syndrome in the past century?. To determine the changes in the expert approach to the management of heroin withdrawal syndrome, as presented in a widely used textbook in the United States.. The chapters on opioid dependence in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.. Opioid replacement taper with morphine (1927-1947), codeine (1931-1943), and methadone (1951-present) administered for 3-10 days has remained the main intervention. The anticholinergic drugs, scopolamine and atropine, were recommended from 1927 to 1943, but their use has never been backed by scientific evidence. Newer approaches relied on clonidine, an alpha-2 receptor agonist used since 1982, and buprenorphine, an opioid agonist/antagonist endorsed for the treatment of heroin withdrawal in 2000.. The pharmacological management of heroin withdrawal syndrome in the past century has progressed from the introduction of methadone to the utilization of clonidine and buprenorphine. More recent advances in treating opioid use disorder have changed the goals of opioid withdrawal management to achievement of abstinence from all opioids to facilitation of long-term treatment with medications for opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Clonidine; Expert Testimony; Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Opioid use disorder (OUD) has become a serious leading health issue in the USA leading to addiction, disability, or death by overdose. Research has shown that OUD can lead to a chronic lifelong disorder with greater risk for relapse and accidental overdose deaths. While the prescription opioid epidemic is a relatively new phenomenon, illicit opioid use via heroin has been around for decades. Recently, additional illicit opioids such as fentanyl have become increasingly available and problematic. We propose a mathematical model that focuses on illicit OUD and includes a class for recovered users but allows for individuals to either remain in or relapse back to the illicit OUD class. Therefore, in our model, individuals may cycle in and out of three different classes: illicit OUD, treatment, and recovered. We additionally include a treatment function with saturation, as it has been shown there is limited accessibility to specialty treatment facilities. We used 2002-2019 SAMHSA and CDC data for the US population, scaled to a medium-sized city, to obtain parameter estimates for the specific case of heroin. We found that the overdose death rate has been increasing linearly since around 2011, likely due to the increased presence of fentanyl in the heroin supply. Extrapolation of this overdose death rate, together with the obtained parameter estimates, predict that by 2038 no endemic equilibrium will exist and the only stable equilibrium will correspond to the absence of heroin use disorder in the population. There is a range of parameter values that will give rise to a backward bifurcation above a critical saturation of treatment availability. We show this for a range of overdose death rate values, thus illustrating the critical role played by the availability of specialty treatment facilities. Sensitivity analysis consistently shows the significant role of people entering treatment on their own accord, which suggests the importance of removing two of the most prevalent SAMHSA-determined reasons that individuals do not enter treatment: financial constraints and the stigma of seeking treatment for heroin use disorder.

Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Mathematical Concepts; Models, Biological; Opioid-Related Disorders; Recurrence

Due to a reduction in the availability of prescription opioids in the United States, the potential transition from prescription opioids to heroin is a public health concern. We assessed trajectories of both nonmedical prescription opioid (NMPO) and heroin use from adolescence (age 18) to adulthood (age 50) and how these trajectories were associated with substance use disorder (SUD) in adulthood (age 35-50).. A national sample of 26,569 individuals from eleven cohorts of US high school seniors (1976-1986) who were followed until age 50 (2008-2018). The analysis focuses on respondents who engaged in past-year NMPO and heroin use. Outcomes included the endorsement of two or more SUD symptoms.. Among NMPO users, 7.5% had used heroin by the age of 50. The latent profile analyses assessing individuals who reported both NMPO and heroin use during the 32-year study period found four unique trajectory groups: (1) "age 18 concurrent use" (81.2%); (2) "mid-30s NMPO-to-heroin use transition" (10.7%); (3) age 19/20 NMPO-to-heroin use transition, followed by 40s heroin-to-NMPO use transition (4.3%); and (4) "mid-20s NMPO-to-heroin use transition" (3.7%). Respondents in the "mid-30s NMPO-to-heroin use transition" trajectory group had the highest odds of indicating two or more SUD symptoms between ages 35-50.. This is the first study to assess NMPO and heroin use trajectories among a national probability-based sample followed from age 18 to 50. The findings suggest that prescription opioid misuse is a risk factor in the development of SUDs and has a long-term impact.

Topics: Adolescent; Adult; Analgesics, Opioid; Heroin; Humans; Middle Aged; Opioid-Related Disorders; Prescription Drug Misuse; Prescriptions; Risk Factors; United States; Young Adult

This commentary discusses the novelty of the preclinical opioid choice model published in Heinsbroek et al., Nat Commun, 2021, and the potential influence of altitude on the reported findings. The studies were performed in the Mile High City of Denver, Colorado, where a unique subpopulation of heroin-choosing rats were noted.

Topics: Analgesics, Opioid; Animals; Heroin; Opioid Epidemic; Opioid-Related Disorders; Rats

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

Serotonin (5-HT) is implicated in the reward processes underlying substance use disorder. Epigenetic and transcriptional mechanisms contribute to the development of addictive states. To examine the potential mechanisms of 5-HT receptor genes in opioid use disorder, we first determined the associations between several single-nucleotide polymorphism (SNPs) in three representative 5-HT receptor genes (HTR1B, HTR2A, and HTR3B) and susceptibility to heroin use disorder in 1731 participants. Gene-gene interactions among these genes were analyzed. After identifying the susceptibility genes and SNPs for heroin use disorder, DNA methylation in the promoter region of these susceptibility genes was compared between 111 healthy controls and 120 patients with heroin use disorder. In addition, associations between the susceptibility SNPs and methylation of the CpG sites and gene promoters with differential methylation between groups were examined. Finally, the function of the susceptibility SNPs in the expression of the corresponding genes was screened. Our results demonstrated that rs6296 in the HTR1B gene was correlated with susceptibility to heroin use disorder. Gene-gene interactions between the HTR1B and HTR2A genes were identified. The CpG sites HTR1B_07 and HTR1B_26 and the promoter region of the HTR1B gene were hypermethylated in patients with heroin use disorder compared with healthy controls. Notably, rs6296 correlated in an allele-specific manner with methylation in the HTR1B gene promoter in the blood and gene expression of the HTR1B gene in the frontal cortex and hypothalamus. SNP rs6296 was associated with opioid use disorder by involving mechanisms of DNA methylation and expression of the HTR1B gene.

Topics: DNA Methylation; Heroin; Humans; Opioid-Related Disorders; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin

The incidence of opioid use disorder (OUD) is increasing worldwide, and the opioid-related overdose crisis is currently a major global challenge. This study investigated the effects of adjuvant laser meridian massage (LMM) in men with OUD undergoing methadone maintenance treatment (MMT).. A case-controlled study was conducted from February 2019 to April 2020. Fourteen men with OUD on MMT were enrolled from an addiction treatment center as an experimental group. An age-matched control group comprising 13 men was also enrolled. The experimental group received LMM on the back, including over the Bladder meridian and Governor Vessel, three times weekly for 4 weeks. The control group received only MMT. Urinary morphine levels, patients' self-reports of the number of episodes or days of heroin use, and visual analog scale scores for heroin craving/refusal to use heroin during the previous week were evaluated. Quality of life was reported using the Short Form (SF)-12v2.. The experimental group showed a significant decrease in heroin use (p < 0.05), whereas the control group showed a significant increase in heroin craving (p < 0.05). The SF-12v2 Health Survey revealed a significant improvement in physical health in the experimental group (P < 0.05).. The results of this study suggest that laser meridian massage can be considered a safe, well-tolerated, and potentially useful adjuvant intervention for opioid use disorder.

Topics: Craving; Heroin; Humans; Lasers; Male; Massage; Meridians; Methadone; Opioid-Related Disorders; Quality of Life

To quantify the healthcare costs associated with opioid use disorder among members in a public healthcare system and compare them with healthcare costs in the general population.. Retrospective cohort study.. Inpatient and outpatient care settings of Israel's largest public healthcare provider (that covers 4.7 million members).. Participants included 1173 members who had a diagnosis of opioid use disorder in the years between 2013 and 2018. Each patient was matched with 10 controls based on age and sex.. The main outcome was monthly healthcare costs.. The mean monthly healthcare cost of members with opioid use disorder was $1102 compared with $211 among controls (5.2-fold difference; 95% CI, 4.6-6.0). After excluding members with heroin related diagnoses before the index date (to focus on prescription opioids), this healthcare cost ratio did not substantially change (4.6-fold; 95% CI, 3.9-5.4). Members with opioid use disorder under the age of 65 years had a cost difference of 6.1-fold (95% CI, 5.2-7.1), whereas those 65 years and older experienced cost difference of 3.4-fold (95% CI, 2.6-4.5), compared with controls. The category with the highest cost for members with opioid use disorder was inpatient services, which was 8.7-fold (95%CI, 7.2-10.4) greater than among controls.. Healthcare costs among individuals with opioid use disorder in Israel's public health system are substantially higher than among controls, at least partially attributable to prescription opioid use disorder. Differences are greater among individuals under 65 years.

Topics: Aged; Analgesics, Opioid; Delivery of Health Care; Health Care Costs; Heroin; Humans; Opioid-Related Disorders; Patient Acceptance of Health Care; Public Health; Retrospective Studies

The diagnostic criteria for opioid use disorder, originally developed for heroin, did not anticipate the surge in prescription opioid use and the resulting complexities in diagnosing prescription opioid use disorder (POUD), including differentiation of pain relief (therapeutic intent) from more common drug use motives, such as to get high or to cope with negative affect. The authors examined the validity of the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5 opioid version, an instrument designed to make this differentiation.. Patients (N=606) from pain clinics and inpatient substance treatment who ever received a ≥30-day opioid prescription for chronic pain were evaluated for DSM-5 POUD (i.e., withdrawal and tolerance were not considered positive if patients used opioids only as prescribed, per DSM-5 guidelines) and pain-adjusted POUD (behavioral/subjective criteria were not considered positive if pain relief [therapeutic intent] was the sole motive). Bivariate correlated-outcome regression models indicated associations of 10 validators with DSM-5 and pain-adjusted POUD measures, using mean ratios for dimensional measures and odds ratios for binary measures.. The prevalences of DSM-5 and pain-adjusted POUD, respectively, were 44.4% and 30.4% at the ≥2-criteria threshold and 29.5% and 25.3% at the ≥4-criteria threshold. Pain adjustment had little effect on prevalence among substance treatment patients but resulted in substantially lower prevalence among pain treatment patients. All validators had significantly stronger associations with pain-adjusted than with DSM-5 dimensional POUD measures (ratios of mean ratios, 1.22-2.31). For most validators, pain-adjusted binary POUD had larger odds ratios than DSM-5 measures.. Adapting POUD measures for pain relief (therapeutic intent) improved validity. Studies should investigate the clinical utility of differentiating between therapeutic and nontherapeutic intent in evaluating POUD diagnostic criteria.

Topics: Analgesics, Opioid; Chronic Pain; Heroin; Humans; Opioid-Related Disorders; Prescriptions

Beginning in the 1990s, nonmedical use of prescription opioids (POs) became a major public health crisis. In response to rising rates of opioid dependence and fatal poisonings, measures were instituted to decrease the prescription, diversion, and nonmedical use of POs including prescription drug monitoring programs (PDMPs), pain clinic laws, prescription duration limits, disciplining doctors who prescribed an excessive number of POs, and the advent of abuse deterrent formulations of POs. This paper explores the unintended effects of these policies in the descriptions of why people who use opioids transitioned from PO to injection or heroin/fentanyl use.. We conducted 148 in-depth-interviews with people who use prescription opioids nonmedically, fentanyl or heroin from a rural, urban and suburban area in three states, Connecticut, Kentucky and Wisconsin. Interviews with people who use opioids (PWUO) focused on how they initiated their opioid use and any transitions they made from PO use to heroin, fentanyl or injection drug use.. The majority of participants reported initiating use with POs, which they used for medical or nonmedical purposes. They described needing to take more POs or switched to heroin or fentanyl as their tolerance increased. As more policies were passed to limit opioid prescribing, participants noticed that doctors were less likely to prescribe or refill POs. This led to scarcity of POs on the street which accelerated the switch to heroin or fentanyl. These transitions likely increased risk of overdose and HIV/HCV infection.. A careful analysis of how and why people say they transitioned from PO to heroin or fentanyl reveals many unintended harms of policy changes to prevent overprescribing and diversion. Results highlight the importance of mitigating harms that resulted from policy changes.

Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Opioid-Related Disorders; Policy; Practice Patterns, Physicians'; Prescriptions

The spread of illegally manufactured opioids, including fentanyl, has brought unprecedented levels of drug overdose deaths in North America. In some markets, illegally manufactured fentanyl (IMF) is essentially displacing heroin, not just being used to adulterate it. It is not possible at this time to provide an accurate point estimate of the amount of IMF consumed in the United States. Yet for various purposes (e.g. assessing changes in production levels and the appropriate role for various supply reduction efforts), it is important to have a sense of scale. This article provides guidance through two thought experiments that provide a hypothetical upper bound on U.S. consumption. The first considers a scenario in which IMF replaces heroin in all illegal opioid markets. The second starts with the number of individuals with an opioid use disorder and considers what total consumption would be if IMF was the only opioid they consumed. Both calculations suggest it is unlikely that the annual consumption of IMF in 2021 could have been more than single digit pure metric tons. For comparison, the most recent best estimates of the amount of cocaine and heroin consumed in the U.S. are 145 and 47 pure metric tons, respectively. The article also raises questions about the limitations of using traditional equianalgesic morphine equivalent dose conversions to estimate the total market consumption of IMF.

Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Opioid-Related Disorders; United States

Since 2013, fentanyl and fentanyl analogs, which are significantly more potent than heroin, have been increasingly prevalent in the opioid drug supply. A need exists to adapt methadone dosing from opioid treatment programs (OTPs) in this era. Current methadone protocols at many clinics in the United States are based on expert consensus documents that were created prior to the introduction of fentanyl into the drug supply and are relatively conservative. To date, most OTP reform efforts have focused on relaxation of regulations for take-homes and have not addressed the need to adapt methadone induction schedules to be more rapid in the fentanyl era, as allowed by current regulations. Written by OTP and inpatient consult service addiction medicine physicians with expertise in OUD treatment from across the United States, the aims of the perspective piece are to: 1) highlight the need to improve OTP care by adapting methadone inductions to the fentanyl era, 2) cite emerging evidence for and examples of experiences of OTPs using more aggressive methadone inductions, and 3) call for research and updated guidelines on safety and best practices for methadone induction.

Topics: Analgesics, Opioid; Fentanyl; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Polysubstance use among people who misuse opioids (PWMO) is highly prevalent, but understudied. We defined, estimated, and analyzed national polysubstance use patterns among PWMO using National Household Survey on Drug Use and Health data (2017-2019).. We obtained estimates of past-month patterns of polydrug use using cluster analysis and latent class/profile analysis. We considered misuse of prescription opioids and use of heroin, cocaine (including crack), marijuana, alcohol, and "other" substances.. We identified a five-cluster solution for binary indicators of past-month use and a six-cluster solution for frequency of use. The largest binary cluster (37%) included misuse of prescription opioids and use of alcohol. The second-largest cluster (15%) included misuse of prescription opioids, alcohol, marijuana, and "other" substances. Among those who used heroin, 36% used methamphetamine. In terms of frequency of use, the largest cluster among people who misuse opioid who used multiple substances (almost 40%) misused prescription pain relievers, alcohol, and marijuana infrequently. The second-largest cluster (23%) used marijuana almost daily and misused prescription pain relievers an average of 6.6 days. PWMO in a cluster of almost daily heroin use indicated use of methamphetamine, marijuana, and prescription opioids. Those who used methamphetamine, were using it more than 15 days a month.. We have developed reference measures of polydrug patterns among US household population and estimated their demographic characteristics. We identified clusters of high-risk polydrug use. These findings have implications for the development of prevention and treatment solutions in the United States.

Topics: Analgesics, Opioid; Heroin; Humans; Methamphetamine; Opioid-Related Disorders; Pain; Prescription Drug Misuse; Prescriptions; Substance-Related Disorders; United States

Opioid use disorder is a chronic brain disease influenced by genetic and epigenetic factors, accounting for approximately 50% of the liability. Adrenergic signaling is involved in opioid use disorder. To demonstrate the associations between methylation alterations in the alpha-1-adrenergic receptor (ADRA1A) gene and opioid use disorder, in the present study, we first examined and compared the methylation levels of 97 CpG sites in the promoter region of the ADRA1A gene in the peripheral blood in 120 patients with heroin use disorder and 111 healthy controls. Correlations between methylation levels and duration of heroin/methadone use were then analyzed. Finally, the predicted binding transcription factors (TFs) and their target sequences in the promoter region of the ADRA1A gene, which include the selected CpG sites, were screened in the JASPAR database. Our results demonstrated that hypermethylation in the promoter region of the ADRA1A gene in the blood was associated with opioid use disorder. Correlations between methylation levels of several CpG sites and duration of heroin/methadone use were observed. TFs TFAP2A and RUNX1 were predicted to bind to the target sequences, which include the CpG sites selected in the current study, in the promoter region of the ADRA1A gene. Our findings further extend the associations between methylation alterations in the ADRA1A gene and opioid use disorder potentially through mechanisms of gene expression regulations in the ADRA1A gene.

Topics: China; CpG Islands; DNA Methylation; Heroin; Humans; Methadone; Opioid-Related Disorders; Promoter Regions, Genetic; Receptors, Adrenergic, alpha-1

Access to and uptake of evidence-based treatment for substance use disorder, specifically opioid use disorder (OUD), are limited despite the high death toll from drug overdose in the United States in recent years. Patient perceived barriers to evidence-based treatment after completion of short-term inpatient medically managed withdrawal programs (detox) have not been well studied. The purpose of the current study is to elicit patients' perspectives on challenges to transition to treatment, including medications for OUD (MOUD), after detox and potential solutions.. We conducted semi-structured interviews (N = 24) at a detox center (2018-2019) to explore patients' perspectives on obstacles to treatment. The study managed the data in NVivo and we used content analysis to identify themes.. Patients' characteristics included the following: 54 % male; mean age 37 years; self-identified as White 67 %, Black 13 %, Latinx 8 %, Native Hawaiian/Pacific Islander 4 %, and other 8 %; heroin use in the past 3 months 67 %; and ever injecting drugs 71 %. Patients identified the following barriers: 1) lack of continuity of care; 2) limited number of detox and residential treatment program beds; 3) unstable housing; and 4) lack of options when choosing a treatment pathway. Solutions proposed by participants included: 1) increase low-barrier access to community MOUD; 2) add case managers at the detox center to establish continuity of care after discharge; 3) increase assistance with housing; and 4) encourage patient participation in treatment decisions.. Patients identified lack of continuity of care, especially care coordination, as a major barrier to substance use treatment. Increasing treatment utilization, including MOUD, necessitates a multimodal approach to continuity of care, low-barrier access to MOUD, and support to address unstable housing. Patients want care that incorporates options and respect for. individualized preferences and needs.

Topics: Adult; Female; Heroin; Humans; Inpatients; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Qualitative Research; Residential Treatment; United States

OxyContin was delisted from Canadian provincial drug formularies in March 2012 and replaced with a reformulated tamper-resistant form of oxycodone (i.e., OxyNeo). We assessed if delisting of OxyContin was associated with changes in the use of unregulated opioids and other substances among people who use opioids (PWUO).. Data were derived from two prospective cohort studies of people who use drugs in Vancouver, BC, Canada from 2006 to 2018. PWUO who had at least one follow-up visit before and after delisting of OxyContin were included. Outcomes of interest were self-reported regular (i.e., at least weekly) use of heroin, non-prescribed prescription opioids, cannabis, methamphetamine, crack cocaine, and powder cocaine during the previous six months. Using quasi-experimental interrupted time series, we fit generalized least squares models to assess participants' immediate and long-term substance use practices after the policy change.. We analyzed data from 1014 participants who contributed to 17457 visits during the study. Following the delisting of OxyContin, heroin use increased immediately by 5.17% (95% confidence intervals [CI]: 0.68 to 9.67) and over time by 0.47% (0.35 to 0.58) per month. Non-prescribed prescription opioid use increased immediately by 1.80% (0.10 to 3.50) and over time by 0.16% (0.12 to 0.19) per month. Cannabis use increased immediately by 4.37% (0.88 to 7.87) and over time by 0.11% (0.02 to 0.19) per month. Methamphetamine use did not increase immediately but increased over time by 0.10% (0.01 to 0.18) per month. Crack cocaine use decreased immediately by 6.13% (-10.94 to -1.69) but not significantly over time. Lastly, powder cocaine use did not increase immediately or over time.. Delisting of OxyContin in BC was not associated with a reduction in unregulated opioid use among PWUO. Our findings point to a shift in substance use patterns of PWUO post-intervention and further highlight the unintended consequences of supply-reduction interventions in addressing the opioid epidemic.

Topics: Analgesics, Opioid; Canada; Cohort Studies; Crack Cocaine; Heroin; Humans; Interrupted Time Series Analysis; Methamphetamine; Opioid-Related Disorders; Oxycodone; Powders; Prospective Studies

Fentanyl has come to dominate the U.S. illicit opioid supply. We aimed to characterize and examine correlates of preferences for fentanyl vs. other opioids among individuals starting OUD treatment.. We interviewed 250 adults initiating buprenorphine treatment with positive fentanyl toxicology at intake. We characterized opioid preferences and examined bivariate associations between opioid preference (preference for heroin, fentanyl, heroin-fentanyl mix, or other opioid) and sociodemographic characteristics, psychosocial factors, and substance use behaviors. We then used multinomial logistic regression to examine factors independently associated with fentanyl preferences.. Over half (52.0 %) of participants preferred fentanyl (21.2 % fentanyl alone, 30.8 % heroin-fentanyl mix). In bivariate comparisons, participants who preferred fentanyl were a higher acuity group with respect to risks and problems in general. In the multinomial logistic regression, people who preferred fentanyl, either alone or mixed with heroin, used non-prescribed buprenorphine less in the 30 days preceding treatment entry compared to people who preferred heroin or other opioids (RRR. Many people with OUD report preferring fentanyl. People who express preference for fentanyl differ substantively from those with other opioid preferences, and may be at elevated risk for poor health outcomes. Understanding preferences surrounding fentanyl could inform treatment and harm reduction interventions.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Overdose; Fentanyl; Heroin; Humans; Opioid-Related Disorders

To determine the prevalence of continued illicit drug use among people enrolled in methadone maintenance treatment (MMT), the association between hepatitis C status and methadone dosage, and the predictors for illicit drug abstinence during MMT.. Clinical records of active opioid dependents who underwent MMT between 1 January 2007 and 31 March 2021 in Hospital Tuanku Fauziah, Perlis, Malaysia were retrospectively reviewed. Data collected included baseline demographics, history of illicit drug use, temporal trend in methadone dosage modulation, and co-use of illicit drugs during the MMT.. A total of 87 patients (mean age, 43.9 ± 8.33 years) were included. Their mean duration of involvement in MMT was 7.8 ± 3.69 years. The most commonly used drug was heroin (88.5%), followed by kratom (51.7%). Between 2019 and 2021, 61 (70.1%) patients had ceased abusing opioid, but 51 (58.6%) patients continued using any of the illicit drugs. Methamphetamine and amphetamine co-use was most common (n = 12, 37.5%). Hepatitis C status was not associated with the current methadone dose (U = 539.5, p = 0.186) or the highest dose required (t = -0.291, df = 74, p = 0.772). No predictor for illicit drug abstinence during MMT was identified. Methadone dose positively correlated with frequency of defaulting treatments (. Among our patients, MMT for opioid dependents cannot sufficiently curb illicit drug use, and there is a shift toward stimulants abuse.

Topics: Adult; Analgesics, Opioid; Hepatitis C; Heroin; Humans; Illicit Drugs; Methadone; Methamphetamine; Middle Aged; Opioid-Related Disorders; Retrospective Studies

Overdose deaths involving opioids and stimulants continue to reach unprecedented levels in the United States. Although significant attention has been paid to the relationship between prescription and illicit opioid use, little work has focused on the association between prescription and illicit stimulant use. Thus, this study explores characteristics of those who use or misuse prescription stimulants and/or opioids and associations with use of cocaine, methamphetamine, and heroin.. We used 2015-2020 data from the National Survey on Drug Use and Health. Using adjusted multivariable logistic regression, we estimated the associations between past year prescription stimulant or prescription opioid prescribed use and misuse; various demographic characteristics; and past-year cocaine, methamphetamine, or heroin use.. From 2015 to 2020, 4.9 and 9.8 million US adults annually reported misusing prescription stimulants and opioids, respectively. Individuals who misused prescription stimulants were more likely to be ages 18-25 (45.8 %; 95 % CI: 44.0-47.5) than individuals who misused prescription opioids (21.7 %; 95 % CI: 20.7-22.7). We observed higher rates of cocaine use among individuals reporting prescription stimulant misuse (12.0 %; 95 % CI: 11.0-12.9) compared to those reporting prescription opioid misuse (5.7 %; 95 % CI: 5.1-6.3, p < 0.001). Heroin use was more common among individuals with prescription opioid misuse (2.1 %; 95 % CI: 1.7-2.2) than prescription stimulant misuse (0.6 %; 95 % CI: 0.4-0.7, p < 0.001). However, rates of methamphetamine use among individuals with prescription stimulant misuse (2.4 %; 95 % CI: 1.9-3.0) did not differ from individuals with prescription opioid misuse (2.1 %; 95 % CI: 1.7-2.5, p = 0.67).. Prescription stimulant misuse, compared to prescription opioid misuse, was associated with higher levels of cocaine use but not methamphetamine use. Treatment providers should consider screening for other substance use disorders among people who report prescription stimulant use or misuse. Additional research should seek to understand the mechanism underlying the different associations between prescription stimulant misuse and cocaine or methamphetamine use.

Topics: Adolescent; Adult; Analgesics, Opioid; Central Nervous System Stimulants; Cocaine; Heroin; Humans; Methamphetamine; Opioid-Related Disorders; Prescription Drug Misuse; Prescriptions; United States; Young Adult

Federally certified opioid treatment programs (OTPs) provide psychosocial counselling in addition to medications for opioid use disorder (MOUDs) using a patient-centered approach in providing substance use disorder treatment. This study explored factors associated with patients' adherence to counselling while receiving MOUD at an OTP. A retrospective cohort design using data on adult patients (n = 1151, 61% females, 39% males) admitted to an OTP from July 1, 2014, to June 30, 2016, was employed. The data were for single episodes of care up to 52 weeks. Survival analysis (cox proportional hazards regression) assessed the relationship of personal characteristics, socio-economic status, payment for services, type of substance use, comprehensive care and social support with counselling for up to a year. Results indicated that age, having services paid for by public means, was associated with counselling adherence. Primary heroin use patients had a higher risk of counselling adherence failure than patients who primarily used non-medicinal prescription substances. Treatment agencies may benefit from funding and using evidence-based practices for primary heroin use patients and young adults to better engage and retain these populations in treatment.

Topics: Analgesics, Opioid; Counseling; Female; Heroin; Humans; Male; Opioid-Related Disorders; Retrospective Studies; Young Adult

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

The authors examined the prevalence of co-occurring opioid use disorder and willingness to engage in treatment among clients of eight Los Angeles County Department of Mental Health outpatient clinics.. Adults presenting for an appointment over a 2-week period were invited to complete a voluntary, anonymous health survey. Clients who indicated opioid use in the past year were offered a longer survey assessing probable opioid use disorder. Willingness to take medication and receive treatment also was assessed.. In total, 3,090 clients completed screening. Among these, 8% had a probable prescription (Rx) opioid use disorder and 2% a probable heroin use disorder. Of the clients with probable Rx opioid use or heroin use disorder, 49% and 25% were female, respectively. Among those with probable Rx opioid use disorder, 43% were Black, 33% were Hispanic, and 12% were White, and among those with probable heroin use disorder, 24% were Black, 22% were Hispanic, and 39% were White. Seventy-eight percent of those with Rx opioid use disorder had never received any treatment, and 82% had never taken a medication for this disorder; 39% of those with heroin use disorder had never received any treatment, and 39% had never received a medication. The strongest predictor of willingness to take a medication was believing that it would help stop opioid use (buprenorphine, β=13.54, p=0.003, and naltrexone long-acting injection, β=15.83, p<0.001).. These findings highlight the need to identify people with opioid use disorder and to educate clients in mental health settings about medications for these disorders.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin; Humans; Male; Mental Health; Naltrexone; Opioid-Related Disorders; Prevalence

Opioid agonist treatment (OAT) is the first-line treatment for opioid dependence. Currently available OAT options comprise oral (methadone and morphine) and sublingual (buprenorphine) routes of administration. In Switzerland and some other countries, severely opioid-dependent individuals with insufficient response to oral or sublingual OAT are offered heroin-assisted treatment (HAT), which involves the provision of injected or oral medical heroin (diacetylmorphine [DAM]). However, many patients on treatment with injectable DAM (i-HAT) suffer from injection-related problems such as deteriorated vein status, ulcerations, endocarditis, and abscesses. Other patients who do not respond to oral OAT do not inject but snort opioids, and are not eligible for i-HAT. For this population, there is no other short-acting OAT with rapid onset of action available unless they switch to injecting, which is associated with higher risks. Nasal DAM (n-HAT) could be an alternative treatment option suitable for both populations of patients.. We present a case series of 3 patients on i-HAT who successfully switched to n-HAT.. This is the first description of the clinical use of the nasal route of administration for HAT. n-HAT may constitute an important risk-reduced rapid-onset alternative to i-HAT. In particular, it may be suited for patients with injection-related complications, or noninjecting opioid-dependent patients failing to respond to oral OAT.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

The Ottawa Inner City Health's Managed Opioid Program is the first, to our knowledge, to pair injectable opioid agonist hydromorphone treatment with assisted housing for people experiencing homelessness with severe opioid use disorder (OUD) and injection drug use. We aimed to describe this program and evaluate retention, health, and social wellbeing outcomes.. We retrospectively assessed the first cohort of clients enrolled in the Managed Opioid Program between August 2017-2018. The primary outcome was retention at 12 months. Secondary outcomes included injectable and oral opioid dose titration, non-prescribed opioid use, overdoses, connection with behavioural health services, and social well-being. Descriptive statistics were used to summarize baseline demographics and secondary outcomes. Actuarial survival analysis was used to assess retention among participants.. The study sample included 26 participants: median age was 36 years, 14 were female, 22 were White, eight had alcohol use disorders, 25 had stimulant use disorders, and all had a history of concurrent psychiatric illness. Retention at 12 months was 77% (95% CI 62-95). Throughout the first-year participants' opioid treatment doses increased. The median daily dose of injectable hydromorphone was 36 mg [17-54 mg] and 156 mg [108-188 mg] at enrollment and one year respectively. The median daily dose of oral opioid treatment was 120-milligram morphine equivalents [83-180 mg morphine equivalents] and 330-milligram morphine equivalents [285-428 mg morphine equivalents] at enrollment and one year respectively. Over half had no overdoses and there were no deaths among participants who remained enrolled. At one year, 45% stopped non-prescribed opioid use, 96% connected to behavioral health services, 73% reconnected with estranged families, and 31% started work or vocational programs.. Individuals with severe OUD engaged in injectable hydromorphone treatment and housing showed high retention in care and substantive improvements in patient-centered health and social well-being outcomes.

Topics: Adult; Alcoholism; Analgesics, Opioid; Canada; Female; Heroin; Housing; Humans; Hydromorphone; Opioid-Related Disorders; Retrospective Studies

The opioid epidemic continues despite the availability of medications, including buprenorphine, for opioid use disorder (OUD); identifying novel and effective treatments is critical for decreasing the prevalence of OUD and ending this crisis. Buprenorphine alone does not markedly attenuate abuse-related effects of nonopioids. Treatment outcomes might be improved by combining buprenorphine with a second medication targeting substance use disorder (SUD), such as lorcaserin, a serotonin. This study investigated the effectiveness of buprenorphine/lorcaserin mixtures to decrease preference for heroin or cocaine in monkeys choosing between food and i.v. infusions.. When saline was available for self-administration, monkeys chose food; when heroin or cocaine was available, monkeys dose-dependently increased choice of infusions. Noncontingent administration of heroin, cocaine, or buprenorphine before sessions increased preference for saline over food. Daily noncontingent administration of buprenorphine increased saline choice, decreased heroin choice, and increased variability across monkeys and sessions; preference for cocaine was not altered. Adding lorcaserin to daily treatment reduced variability such that choice of saline and heroin was consistently less than 20%; choice of cocaine did not change.. Because buprenorphine/lorcaserin mixtures would not likely alter abuse of cocaine, they might not be useful for treating SUDs; nevertheless, mixtures reduced variability and decreased preference for heroin, compared with buprenorphine alone, perhaps suggesting that a different drug mixture, in which buprenorphine is combined with a second, nonopioid drug, might offer advantages over treatment with buprenorphine alone.

Topics: Animals; Benzazepines; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Heroin; Macaca mulatta; Opioid-Related Disorders; Self Administration

Gender differences in the prevalence of opioid misuse continue to evolve and have not been well characterized in recent years. Our objective was to investigate gender differences in the prevalence of opioid misuse and use disorder in the US over the 5-year period from 2015 to 2019.. We used annual survey data from the 2015-2019 National Survey on Drug Use and Health to estimate gender differences in the prevalence of opioid misuse. We examined past-year opioid analgesic misuse initiation, opioid analgesic misuse, heroin use, opioid analgesic use disorder and heroin use disorder. Logistic regression models were used to test gender differences, adjusting for sociodemographic variables.. In adjusted analyses, women had higher odds of having initiated opioid analgesic misuse in the past year compared to men. In contrast, men had higher odds of misuse of opioid analgesics, heroin use, and an opioid analgesic or heroin use disorder.. Although opioid misuse has historically been more prevalent in men, the gender difference in opioid analgesic misuse continues to narrow, with more women initiating misuse than men including higher rates of misuse in adolescent girls. Heroin use continues to be approximately twice as common in men as women.

Topics: Adolescent; Analgesics, Opioid; Female; Heroin; Humans; Male; Opioid-Related Disorders; Prescription Drug Misuse; Prevalence; Sex Factors; United States

This article examines injectable Opioid Agonist Treatment (iOAT), in which patients suffering from long-term, treatment refractory opioid use disorder (OUD) are prescribed injectable diacetylmorphine, the active ingredient of heroin. While iOAT is part of the continuum of care for OUD in some European countries and in some parts of Canada, it is not an available treatment in the United States. We suggest that one reason for this situation is the belief that a genuine treatment for substance use disorder cannot prescribe the same substance as that used. We examine possible rationales for this belief by considering four combinations of views on the constitutive causal basis of substance use disorders and the definition of effective treatment. We show that all but one combination counts iOAT as a genuine treatment and that there are good reasons to reject the one that does not. Specifically, we claim that medical interventions, such as iOAT, that significantly reduce the severity of a disorder deserve to be categorized as effective treatments and regarded as such in practice.

Topics: Analgesics, Opioid; Canada; Ethics, Clinical; Europe; Heroin; Humans; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Substance-Related Disorders; United States

To determine the association between the abuse-deterrent reformulation of OxyContin and adolescent lifetime heroin use in the United States.. The quasi-experimental study uses individual survey data from the 1999-2019 Youth Risk Behavior Surveillance System to examine whether the reformulation of OxyContin in August 2010 affected adolescent lifetime heroin use, exploiting heterogeneity in state-level rates of OxyContin misuse before the reformulation. Multiple regression analysis adjusted for state and year fixed effects, adolescent demographics, and time-varying state characteristics and policies.. The release of the abuse-deterrent reformulation of OxyContin was associated with a reduction in adolescents reporting ever using heroin. An adolescent in a state with a one percentage point higher state-level rate of pre-reformulation OxyContin misuse was 1.7% points less likely to report ever using heroin after the reformulation (95% confidence interval, [(CI) = -0.007, -0.027]). These effects are strongest for adolescent males (estimate: -0.028, [(CI) = -0.016, 0.040]) and non-whites (estimate: -0.021, [(CI) = -0.005, -0.037]).. These results suggest the release of abuse-deterrent OxyContin is associated with a decrease in the likelihood of adolescent lifetime heroin use in states with higher pre-reformulation rates of OxyContin misuse. Pharmaceutical innovations and policies that reduce the likelihood of prescription opioid misuse may be effective in reducing adolescent lifetime heroin use.

Topics: Adolescent; Analgesics, Opioid; Heroin; Humans; Male; Opioid-Related Disorders; Oxycodone; Surveys and Questionnaires; United States

Deaths involving illicitly manufactured fentanyl (IMF) have increased since 2013 in the United States. Little research has examined individuals using IMF. This study aims to explore the characteristics of US adults who used IMF, heroin, or misused prescription opioids and examine the associations between demographic, clinical, psychosocial characteristics and IMF use.. A convenience sample of adults aged ≥ 18 years being assessed for substance use disorder (SUD) treatment was collected between January-December 2019 using the Addiction Severity Index-Multimedia Version instrument. We used a multivariable logistic regression model to examine the associations between demographic, clinical, psychosocial characteristics and IMF use.. Adults reporting IMF as their primary lifetime substance use problem also reported using other substances-most often alcohol or heroin-both in the past 30 days and during their lifetime. Characteristics associated with increased odds of reporting IMF as the primary lifetime substance use problem included age 18-24 years (adjusted odds ratio (aOR) = 1.68; 95% confidence interval (CI) = 1.18-2.38) versus 45-54 years, non-Hispanic Black persons (aOR = 1.44; 95% CI = 1.11-1.85) versus non-Hispanic White persons, being assessed in Northeast (aOR = 15.46; 95% CI = 8.67-27.56) versus West, and having a history of at least one lifetime overdose (1 overdose (aOR = 1.91; 95% CI = 1.49-2.44); 2 overdoses (aOR = 1.95; 95% CI = 1.48-2.58); 3 or more overdoses (aOR = 2.27; 95% CI = 1.82-2.82)).. These findings provide new insights into this high-risk population and help identify strategies to address increasing overdose death rates involving IMF. Opportunities for intervention include expanding naloxone distribution and harm reduction programs and connecting individuals with nonfatal overdoses to SUD treatment.

Topics: Adolescent; Adult; Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Opioid-Related Disorders; United States; Young Adult

The use of prescription opioids is a matter of concern among academics and practitioners, but there remains a lack of programming to target this issue. One program, This Is (Not) About Drugs (TINAD), is intended to address part of this need by altering youth perceptions of the risks associated prescription opioid misuse as well as heroin. This study presents results from a quasi-experimental evaluation of TINAD. Propensity score matching techniques were used to account for selection effects across treatment and comparison groups. Program participants demonstrated increases in understanding of the similarities between prescription opioids and heroin and the risks associated with prescription opioid misuse. While these results are promising, TINAD requires a more rigorous evaluation of its effectiveness.

Topics: Adolescent; Analgesics, Opioid; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Schools

Prescription drug monitoring programs (PDMPs) are tools that states can use to fight prescription opioid misuse within their jurisdiction. However, because PDMPs make prescription opioids more difficult to access, these programs may have the unintended consequence of increasing deaths related to illicit opioids.

Topics: Analgesics, Opioid; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Prescription Drug Monitoring Programs; Prescriptions; United States

Opioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of females. In this study, male and female rats self-administered heroin (maintenance dose of 12.5 μg/kg/infusion) and opioid withdrawal after abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hr after the last self-administration session. Total somatic signs increased until 48 hr (predominantly in females), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hr, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hr after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though females displayed significantly higher body temperature at all timepoints compared with males, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology after self-administration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Topics: Animals; Female; Heroin; Male; Narcotics; Opioid-Related Disorders; Rats; Self Administration; Substance Withdrawal Syndrome

Increasing naloxone awareness and carrying among individuals who misuse opioid analgesic medications (OAs) could reduce opioid overdose mortality.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Heroin; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

To determine the association between self-reported heroin initiation and patterns of prescription opioid use.. Using linked Oregon Medicaid, prescription drug monitoring program, and Treatment Episodes Data Set data, we conducted a case-control study of individuals reporting heroin initiation between 2015 and 2017 during treatment intake. Prescription drug monitoring program data provided prescription opioid use patterns, including long-term prescription opioid therapy, in the year before self-reported heroin initiation. Four controls were matched to each case on aggregate prescription opioid use and demographics.. About half (49%) of individuals who reported heroin initiation filled an opioid in the year before initiation. Individuals who initiated heroin (n = 306) were more likely to receive prescriptions from multiple prescribers (24% vs 18%, P = 0.007) and pharmacies (12% vs 5%, P < 0.001) compared with matched controls (n = 1224). Long-term opioid therapy (13% vs 14%, P = 0.74) was uncommon and did not differ between groups.. Although prescription opioid use commonly preceded self-reported heroin initiation, long-term opioid therapy was not common. Although this study did not find an association between opioid discontinuation and heroin initiation, sample size and follow-up limitations preclude definitive conclusions. Efforts to limit prescription opioids should continue to evaluate for unintended harms.

Topics: Analgesics, Opioid; Case-Control Studies; Heroin; Humans; Opioid-Related Disorders; Prescriptions; Self Report; United States

The inability to maintain drug abstinence is often referred to as relapse and consists of a process by which an abstaining individual slips back into old behavioral patterns and substance use. Animal models of relapse have been developed over the last decades and significantly contributed to shed light on the neurobiological mechanisms underlying vulnerability to relapse. The most common procedure to study drug-seeking and relapse-like behavior in animals is the "extinction-reinstatement model." Originally elaborated by Pavlov and Skinner, the concepts of reinforced operant responding were applied to addiction research not before 1971 (Stretch et al., Can J Physiol Pharmacol 49:581-589, 1971), and the first report of a reinstatement animal model as it is now used worldwide was published only 10 years later (De Wit and Stewart, Psychopharmacology 75:134-143, 1981). According to the proposed model, opioids are typically self-administered intravenously, as humans do, and although rodents are most often employed in these studies, a variety of species including nonhuman primates, dogs, cats, and pigeons can be used. Several operant responses are available, depending on the species studied. For example, a lever press or a nose poke response typically is used for rodents, whereas a panel press response typically is used for nonhuman primates. In this chapter we describe a simple and easily reproducible protocol of heroin-seeking reinstatement in rats, which proved useful to study the neurobiological mechanisms underlying relapse to heroin and vulnerability factors enhancing the resumption of heroin-seeking behavior.

Topics: Administration, Intravenous; Analgesics, Opioid; Animals; Behavior Control; Behavior, Addictive; Conditioning, Operant; Cues; Disease Models, Animal; Drug-Seeking Behavior; Heroin; Infusions, Intravenous; Male; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reinforcement, Psychology; Reward; Self Administration; Substance-Related Disorders

Topics: Analgesics, Opioid; Fentanyl; Heroin; Humans; Opioid-Related Disorders

Cocaine use is prevalent among people receiving injectable opioid agonist treatment. Investigations of cocaine use in this population have been descriptive and the potential heterogeneity existing in patterns of use have not been characterized. As such, among patients receiving injectable opioid agonist treatment, this study aimed to: 1) quantify intra- and inter-individual variation in cocaine use over 24-months and; 2) determine how predictors of interest explained this variation.. Participants were patients receiving injectable opioid agonist treatment for opioid use disorder. Study visits were completed at baseline prior to receiving treatment, and 3,6,9,12,18, and 24 months after baseline. A multi-level regression approach to growth curve modeling was employed to estimate and explain intra- (within-person) and inter-individual (between-person) variation in cocaine use.. Significant intra and inter-individual variation in cocaine use was identified over 24-months. Treatment engagement was on average associated with reductions in the prior month number of days of cocaine use (range: 0-30)(Estimate (standard error): -0.05(0.02), p = 0.003). On average, men reported less cocaine use compared to women (Estimate (standard error): -5.91(1.57), p=<0.001), and participants reporting ever regularly using cocaine at baseline reported more cocaine use over 24-months compared to participants reporting never regularly using cocaine (Estimate (standard error): 4.72 (1.91), p = 0.013).. Significant reductions in cocaine use were observed and significant heterogeneity in patterns of cocaine use was identified. These heterogeneous cocaine use profiles suggest that an individualized approach to care will be critical in responding to patients' cocaine use in injectable opioid agonist treatment.

Topics: Adult; Analgesics, Opioid; Cocaine; Cocaine-Related Disorders; Female; Heroin; Humans; Hydromorphone; Male; Middle Aged; Opioid-Related Disorders

The nearly insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters, existing small-molecule drugs continue to inadequately address OUD due to their engagement of the opioid receptor, which can leave the user to deal with side effects and financial hardships from their repeated use. An alternative therapeutic approach utilizes endogenously generated antibodies through active vaccination to reduce the effect of opioids without modulating the opioid receptor. Here, we explore different adjuvants and storage conditions to improve opioid vaccine efficacy and shelf life. Our results revealed that inulin-based formulations (Advax) containing a CpG oligodeoxynucleotide (ODN) acted as effective adjuvants when combined with a heroin conjugate: immunized mice showed excellent recovery from heroin-induced antinociception accompanied by high titer, high opioid affinity serum antibodies similar to the immunopotentiating properties of traditional alum-based adjuvants. Moreover, nonhuman primates vaccinated with a heroin/fentanyl combination vaccine demonstrated potent antibody responses against opioids when formulated with both inulin and alum adjuvants. Finally, storing a freeze-dried opioid vaccine formulation maintained efficacy for up 1 year at room temperature. The results from our studies represent an advance toward a clinically feasible opioid vaccine.

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Analgesics, Opioid; Animals; Fentanyl; Heroin; Immunization; Male; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Opioid-Related Disorders; Vaccination; Vaccines, Conjugate

Although rates of nonmedical opioid use are highest in late adolescence and emerging adulthood, efforts to understand the extent of the heterogeneity in opioid misuse during this time have been limited. The current study aimed to derive and define typologies of opioid use in high school students at the onset of emerging adulthood.. Survey responses from a statewide sample of high school students aged 18 and 19 (N = 26,223) were analyzed. Group-based comparisons between participants reporting opioid use and those not reporting opioid use were conducted. Among those reporting opioid use (n = 1,636), we conducted a latent class analysis (LCA) to identify heterogeneous subgroups of opioid users on the basis of non-medical use of prescription opioids (NMUPO) and heroin use. The resulting classes were then compared across various risk and protective factors using multinominal logistic regression.. Consistent differences were observed between participants using opioids and participants not using opioids, with moderate to large effect sizes. Results from LCA revealed three subclasses: NMUPO-Any Use, NMUPO To Get High, and Heroin Use. Subclass differences were observed for non-opioid substance use, mental health, and demographics.. Findings from this study underscore the variability of youth who engage in opioid use in late adolescence. Results also indicate that opioid use during adolescence is likely indicative of a broader set of substance use and mental health issues.

Topics: Adolescent; Adult; Analgesics, Opioid; Heroin; Humans; Latent Class Analysis; Opioid-Related Disorders; Prescription Drug Misuse; Prescriptions; Young Adult

The current opioid crisis and associated heroin epidemic have exhausted the limited community services that are available to substance users, with only about 12% of substance use treatment facilities offering special programs for pregnant women. Little information is known about the lived experience of postpartum women in outpatient substance use treatment programs, who are working toward abstinence and caring for a newborn. The purpose of this phenomenological study was to explore the lived experience of postpartum women attending outpatient substance use treatment for illicit opioid or heroin use.. Individual interviews were conducted between December 2017 and November 2018, with 10 postpartum women with opioid use disorder (OUD) engaged in outpatient substance use treatment programs. A 4-step conceptual framework as suggested by Moustakas was used to understand and synthesize the lived experiences shared by the women.. Five themes emerged from the raw data: the presence of a stigma in providers of health care services, a fear of being reported to family services, children are primary motivators to remain engaged in treatment, concern for the welfare of the infant, and barriers to treatment.. Postpartum women with OUD and their infants have complex needs that may best be served by treatment programs that offer comprehensive care. The fear of being reported to family services and possible loss of custody influenced all aspects of their decision-making.

Topics: Analgesics, Opioid; Child; Female; Heroin; Humans; Infant; Infant, Newborn; Opioid-Related Disorders; Outpatients; Postpartum Period; Pregnancy

Analyze 10-year trends in opioid use disorder with heroin (OUD-H) among older persons and to compare those with typical-onset (age <30 years) to those with late (age 30+) onset.. Naturalistic observation using the most recent (2008-2017) Treatment Episode Data Set-Admissions (TEDS-A).. Admission records in TEDS-A come from all public and private U.S. programs for substance use disorder treatment receiving public funding.. U.S. adults aged 55 years and older entering treatment for the first time between 2008 and 2017 to treat OUD-H.. Admission trends, demographics, substance use history.. The number of older adults who entered treatment for OUD-H nearly tripled between 2007 and 2017. Compared to those with typical-onset (before age 30), those with late-onset heroin use were more likely to be white, female, more highly educated, and rural. Older adults with late-onset were more likely to be referred to treatment by an employer and less likely to be referred by the criminal justice system. Those with late-onset were more likely to use heroin more frequently but less likely to inject heroin than those with typical-onset. Those with typical onset were more likely to receive medication for addiction treatment than those with late-onset.. Late-onset heroin use is increasing among older U.S. adults. Research is needed to understand the unique needs of this population better. As this population grows, geriatric psychiatrists may be increasingly called upon to provide specialized care to people with late-onset OUD-H.

Topics: Adult; Aged; Aged, 80 and over; Female; Heroin; Hospitalization; Humans; Middle Aged; Opioid-Related Disorders; Referral and Consultation

There is a lack of understanding of what contributes to attitudes toward individuals with an opioid addiction and preferences for policies that support them.. This study aimed to investigate stigmatization of an opioid addiction and support for publicly funded drug treatment. A randomized, between-subjects case vignette study (N = 1998) was conducted with a nation-wide online survey. To assess public perceptions of stigma and support for publicly funded drug treatment, participants rated a hypothetical individual who became addicted to prescription opioids across three conditions: 1) male or female, 2) an individual who was prescribed prescription painkillers or took prescription painkillers from a friend and 3) an individual who transitioned to using heroin or who continued using prescription painkillers.. Our results showed that there were stronger negative attitudes towards a male (p < .01) and toward an individual who took prescription painkillers from a friend (all p's < .05), and both stronger positive and negative attitudes toward an individual who transitioned to heroin from prescription painkillers (all p's < .05). Next, we demonstrated that the probability that someone supports publicly funded drug treatment increases by 3.6 percentage points for each unit increase along a 12-point scale of positive attitudes (p < .0005), 1.3 percentage points for each unit decrease along a 12-point scale of negative attitudes (p < .005), 7.3 percentage points for each unit increase along a 6-point scale of perceived treatment efficacy (p < .0001), 0.1 percentage points for each unit decrease along a 100-point scale that measures the strength of one's belief that addiction is controllable (p < .005) and 0.2 percentage points for each unit decrease along a 100-point scale that measures the strength of one's belief that income is controllable (p < .005). Lastly, when controlling for the effects of stigma, the probability of supporting publicly funded drug treatment decreases by 6.3 percentage points (p < 0.001) when an individual was prescribed prescription painkillers from a doctor. However, path analysis identified a channel through which a doctor's prescription increased support for publicly funded drug treatment by influencing positive attitudes, negative attitudes, and responsibility.. Our findings provide further evidence that information about individuals who become addicted to opioids can influence stigma perceptions and support for publicly funded drug treatment.

Topics: Analgesics, Opioid; Female; Heroin; Humans; Male; Opioid-Related Disorders; Policy; Prescriptions

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

The study examined associations between medication assisted treatment (MAT) and psychiatric symptom severity, measured by Positive and Negative Symptom Scale (PANSS), among individuals with serious mental illness and a history of heroin use. Of 271 participants, 32% (n=87) reported a history of heroin use and, of those, 14.9% (n=13) reported MAT. Higher scores in PANSS Total, Negative, and Disordered subscales were associated with lower odds, while being on an antipsychotic with higher odds, of receiving MAT. This supports the greater need for clinician attention to different symptom clusters and targeted multidimensional interventions as a way to increase MAT participation.

Topics: Adult; Antipsychotic Agents; Female; Heroin; Humans; Male; Mental Disorders; Middle Aged; Opioid-Related Disorders

Since late 2014, fentanyl has become the major driver of opioid mortality in the United States. However, a descriptive analysis of fentanyl victims is limited. We studied the 2016 fentanyl and heroin overdose deaths and compared them to previously studied heroin-associated fatalities from 2012 over a wide range of demographic and investigative variables, including overdose scene findings, toxicology results, and prescription drug history. We observed a significant increase in fentanyl-related deaths (n = 421, 2016) versus heroin deaths (n = 160, 2012) but the baseline demographics between both cohorts remained similar. Victims were predominantly of ages 35-64 years (60%-64%), White (83%-85%), and male (73%-76%). 2016 fentanyl decedents were more likely to have naloxone administered upon overdose, and the majority still had a positive prescription history for a controlled substance. Toxicology data showed a decrease in mean morphine and 6-monoacetylmorphine concentrations when cointoxication with fentanyl occurred. Our study emphasizes the medical examiner's role as a public health data source and bridge between different stakeholders combating the opioid epidemic.

Topics: Adult; Age Distribution; Coroners and Medical Examiners; Drug Overdose; Drug Prescriptions; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Middle Aged; Naloxone; Narcotic Antagonists; Ohio; Opioid-Related Disorders; Racial Groups; Sex Distribution

Topics: Aged; Heroin; Humans; Opioid-Related Disorders; Surveys and Questionnaires

We assessed prevalence and correlates for hepatitis C virus (HCV) infection in young adult people who inject drugs (PWID) in rural New Mexico, where opioid use has been historically problematic.. Participants were 18-29 years old with self-reported injection drug use in the past 90 days. We conducted testing for HCV antibodies (anti-HCV) and HCV ribonucleic acid (RNA) and assessed sociodemographic and risk exposures. We provided counseling and referrals to prevention services and drug treatment. We estimated prevalence ratios (PR) to assess bivariate associations with HCV infection; and adjusted PRs using modified Poisson regression methods.. Among 256 participants tested for anti-HCV, 156 (60.9 %) had been exposed (anti-HCV positive), and of 230 tested for both anti-HCV and HCV RNA, 103 (44.8 %) had current infection (RNA-positive). The majority (87.6 %) of participants were Hispanic. Almost all (96.1 %) had ever injected heroin; 52.4 % and 52.0 % had ever injected methamphetamine or cocaine, respectively. Polysubstance injecting (heroin and any other drug) was associated with significantly higher prevalence of HCV infection (76.0 %) compared to injecting only heroin (24.0 %) (PR: 3.17 (95 % CI:1.93, 5.23)). Years of injecting, history of non-fatal opioid-involved overdose, polysubstance injecting, and stable housing were independently associated with HCV infection.. HCV is highly prevalent among young adult PWID in rural NM. The high reported prevalence of polysubstance injecting and its association with HCV infection should be considered in prevention planning.

Topics: Adolescent; Adult; Female; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Heroin; Humans; Male; New Mexico; Opioid-Related Disorders; Pharmaceutical Preparations; Prevalence; Risk Factors; Rural Population; Substance Abuse, Intravenous; Young Adult

Topics: Aged; Heroin; Humans; Opioid-Related Disorders; Substance-Related Disorders; Surveys and Questionnaires

People who use opioids and people living with HIV (PLWH) are at increased risk for liver-related morbidity and mortality. Although animal models suggest that chronic opioid use may cause liver damage, research in humans is limited. We aimed to determine whether opioid use, particularly heroin, was associated with liver fibrosis.. Cross-sectional analysis of 679 participants (295 HIV/HCV uninfected, 218 HIV mono-infected, 87 HCV mono-infected, 79 HIV/HCV coinfected) from the Miami Adult Studies on HIV (MASH) cohort. Liver fibrosis was assessed via magnetic resonance elastography (MRE) on a 3 T Siemens MAGNETOM Prisma scanner.. A total of 120 (17.7 %) participants used opioids. Liver fibrosis was present in 99 (14.6 %) participants and advanced liver fibrosis in 31 (4.6 %). Heroin use (N = 46, 6.8 %) was associated with HCV-seropositivity, smoking, misuse of prescription opioids, and polysubstance use. The use of heroin, but not misuse of prescription opioids, was significantly associated with liver fibrosis (OR = 2.77, 95 % CI: 1.18-6.50) compared to heroin non-users, after adjustment for confounders including excessive alcohol consumption, polysubstance use and HIV and HCV infections. Both HIV and HCV infections were associated with liver fibrosis, whether virally suppressed/undetectable or viremic.. Heroin use was independently associated with increased risk for liver fibrosis irrespective of the use of other substances and HIV or HCV infections. Both HIV and HCV were associated with higher risk for liver fibrosis, even among those with suppressed or undetectable viral loads. The exact mechanisms for opioid-induced liver fibrosis remain to be fully elucidated.

Topics: Adult; Analgesics, Opioid; Cohort Studies; Cross-Sectional Studies; Female; Florida; Hepatitis C; Heroin; HIV Infections; Humans; Liver Cirrhosis; Male; Middle Aged; Opioid-Related Disorders; Viral Load

This paper examines how the recent transition of the opioid crisis from prescription opioids to more prevalent misuse of illicit opioids, such as heroin and fentanyl, altered labor supply behavior and disability insurance claiming rates. We exploit differential geographic exposure to the reformulation of OxyContin, the largest reduction in access to abusable prescription opioids to date, to study the effects of substitution to illicit markets. We observe meaningful reductions in labor supply measured in terms of employment-to-population ratios, hours worked, and earnings in states more exposed to reformulation relative to those less exposed. We also find evidence of increases in disability applications and beneficiaries.

Topics: Analgesics, Opioid; Heroin; Humans; Opioid-Related Disorders; Oxycodone; United States; Workforce

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

In this paper, I propose a life cycle model of painkiller consumption that combines the theory of health deficit accumulation with the theory of addiction. Chronic pain is conceptualized as a persistent negative shock to lifetime utility that can be treated by pain relief medication. Individuals treated with opioid pain relievers (OPR) develop addiction, which increases their demand for opioids and reduces their welfare and life expectancy through side effects and potential overdose. I calibrate the model for a benchmark American and investigate the comparative dynamics of alternative drug characteristics, pain intensities, and ages of onsets of pain as well as their implications for welfare and life expectancy. Computational experiments are used to identify fully rational and imperfectly rational addiction behavior. Fully rational addicts reduce OPR use when new information about the addictive potential of these drugs arrives. Imperfectly rational addicts further develop their addiction and switch to illicit opioid use. Likewise, a discontinued prescription helps fully rational addicts to quit quickly, while it induces imperfectly rational individuals to take up heroin. I also discuss treatment of OPR addiction and the use of opioids in palliative care.

Topics: Analgesics, Opioid; Heroin; Humans; Longevity; Opioid-Related Disorders; Pain; United States

Understanding whether International Classification of Disease, 10th Revision, Clinical Modification (ICD-10-CM) codes can be used to accurately detect substance use can inform their use in future surveillance and research efforts.. Using 2015-2018 data from a retrospective cohort study of 602 safety-net patients prescribed opioids for chronic non-cancer pain, we calculated the sensitivity and specificity of using ICD-10-CM codes to detect illicit substance use compared to retrospective self-report by substance (methamphetamine, cocaine, opioids [heroin or non-prescribed opioid analgesics]), self-reported use frequency, and type of healthcare encounter.. Sensitivity of ICD-10-CM codes for detecting self-reported substance use was highest for methamphetamine (49.5 % [95 % confidence interval: 39.6-59.5 %]), followed by cocaine (44.4 % [35.8-53.2 %]) and opioids (36.3 % [28.8-44.2 %]); higher for participants who reported more frequent methamphetamine (intermittent use: 27.7 % [14.6-42.6 %]; ≥weekly use: 67.2 % [53.7-79.0 %]) and opioid use (intermittent use: 21.4 % [13.2-31.7 %]; ≥weekly use: 52.6 % [40.8-64.2 %]); highest for outpatient visits (methamphetamine: 43.8 % [34.1-53.8 %]; cocaine: 36.8 % [28.6-45.6 %]; opioids: 33.1 % [25.9-41.0 %]) and lowest for emergency department visits (methamphetamine: 8.6 % [4.0-15.6 %]; cocaine: 5.3 % [2.1-10.5 %]; opioids: 6.3 % [3.0-11.2 %]). Specificity was highest for methamphetamine (96.4 % [94.3-97.8 %]), followed by cocaine (94.0 % [91.5-96.0 %]) and opioids (85.0 % [81.3-88.2 %]).. ICD-10-CM codes had high specificity and low sensitivity for detecting self-reported substance use but were substantially more sensitive in detecting frequent use. ICD-10-CM codes to detect substance use, particularly those from emergency department visits, should be used with caution, but may be useful as a lower-bound population measure of substance use or for capturing frequent use among certain patient populations.

Topics: Adult; Analgesics, Opioid; Chronic Pain; Cocaine; Emergency Service, Hospital; Female; Heroin; Humans; Illicit Drugs; International Classification of Diseases; Male; Methamphetamine; Middle Aged; Opioid-Related Disorders; Retrospective Studies; Self Report; Sensitivity and Specificity; Substance-Related Disorders

Estimates from the National Survey on Drug Use and Health (Substance Abuse and Mental Health Services Administration [SAMHSA], 2019) suggest 3.6% of persons aged 12 and older misused prescription pain relievers in the past year and 0.3% used heroin. However, research suggests that most individuals drastically overestimate rates of substance use and misuse. Those who overestimate substance misuse are often more likely to misuse substances themselves (Kilmer et al., 2015; McCabe, 2008).

Topics: Adult; Analgesics, Opioid; Female; Heroin; Humans; Opioid-Related Disorders; Pain; Prescription Drug Misuse; Prescriptions

To characterize racial/ethnic differences in past-year prescription opioid misuse and heroin use.. Data on 1,117,086 individuals age 12 and older were from the 1999-2018 National Survey on Drug Use and Health. We compared relative prevalences across 6 racial/ethnic groups for prescription opioid misuse analyses and 4 racial/ethnic groups for heroin analyses. Unadjusted and gender- and age-adjusted prevalences are reported for 5 time periods (1999-2002, 2003-2006, 2007-2010, 2011-2014, 2015-2018). Survey-weighted Poisson regression models with robust variance were used to estimate risk ratios by race/ethnicity and to test for time trends.. Prescription opioid misuse was significantly higher among non-Hispanic White individuals than among Black, Hispanic, and Asian individuals across all time periods, yet was highest among Native American individuals in every time period. The relative difference between White and both Hispanic and Asian individuals significantly widened over time, whereas the gap between Black and White individuals significantly decreased. Early in the study period, heroin use was highest among Black and Hispanic individuals. Heroin use among White individuals first surpassed all other groups in 2007-2010 and continued to steadily increase, more than doubling from 1999-2002 to 2015-2018.. While heroin use has risen among all racial/ethnic groups, the demographics of heroin use have changed significantly in the past two decades such that prevalence is now highest among White individuals. Opioid prevention and treatment initiatives should both be informed by the changing demographics of heroin use and seek to reduce opioid-related harms and expand treatment access equitably for all racial/ethnic groups.

Topics: Adult; Analgesics, Opioid; Black or African American; Child; Ethnicity; Female; Heroin; Hispanic or Latino; Humans; Male; Middle Aged; Opioid-Related Disorders; Prevalence; Surveys and Questionnaires; United States; White People

Topics: Aged; Heroin; Humans; Opioid-Related Disorders; Surveys and Questionnaires

Opioid overdose related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP). To discover trends and patterns of opioid poisoning and the demographic and regional disparities, we analyzed large scale patient visits data in New York State (NYS). Demographic, spatial, temporal and correlation analyses were performed for all OP patients extracted from the claims data in the New York Statewide Planning and Research Cooperative System (SPARCS) from 2010 to 2016, along with Decennial US Census and American Community Survey zip code level data. 58,481 patients with at least one OP diagnosis and a valid NYS zip code address were included. Main outcome and measures include OP patient counts and rates per 100,000 population, patient level factors (gender, age, race and ethnicity, residential zip code), and zip code level social demographic factors. The results showed that the OP rate increased by 364.6%, and by 741.5% for the age group > 65 years. There were wide disparities among groups by race and ethnicity on rates and age distributions of OP. Heroin and non-heroin based OP rates demonstrated distinct temporal trends as well as major geospatial variation. The findings highlighted strong demographic disparity of OP patients, evolving patterns and substantial geospatial variation.

Topics: Adolescent; Adult; Age Distribution; Aged; Analgesics, Opioid; Drug Overdose; Epidemics; Female; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Retrospective Studies; Young Adult

In North America the opioid poisoning crisis currently faces the unprecedented challenges brought by the COVID-19 pandemic, further straining people and communities already facing structural and individual vulnerabilities. People with opioid use disorder (OUD) are facing unique challenges in response to COVID-19, such as not being able to adopt best practices (e.g., physical distancing) if they're financially insecure or living in shelters (or homeless). They also have other medical conditions that make them more likely to be immunocompromised and at risk of developing COVID-19. In response to the COVID-19 public health emergency, national and provincial regulatory bodies introduced guidance and exemptions to mitigate the spread of the virus. Among them, clinical guidance for prescribers were issued to allow take home opioid medications for opioid agonist treatment (OAT). Take Home for injectable opioid agonist treatment (iOAT) is only considered within a restrictive regulatory structure, specific to the pandemic. Nevertheless, this risk mitigation guidance allowed carries, mostly daily dispensed, to a population that would not have access to it prior to the pandemic. In this case it is presented and discussed that if a carry was possible during the pandemic, then the carry could continue post COVID-19 to address a gap in our approach to individualize care for people with OUD receiving iOAT.. Here we present the first case of a patient in Canada with long-term OUD that received take home injectable diacetylmorphine to self-isolate in an approved site after being diagnosed with COVID-19 during a visit to the emergency room where he was diagnosed with cellulitis and admitted to receive antibiotics.. In the present case we demonstrated that it is feasible to provide iOAT outside the community clinic with no apparent negative consequences. Improving upon and making permanent these recently introduced risk mitigating guidance during COVID-19, have the potential not just to protect during the pandemic, but also to address long-overdue barriers to access evidence-based care in addiction treatment.

Topics: Administration, Intravenous; Administration, Oral; Analgesics, Opioid; COVID-19; Heroin; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; SARS-CoV-2

The opioid epidemic has caused an increase in overdose deaths which can be attributed to fentanyl combined with various illicit substances. Drug checking programs have been started by many harm reduction groups to provide tools for users to determine the composition of their street drugs. Immunoassay fentanyl test strips (FTS) allow users to test drugs for fentanyl by either filling a baggie or cooker with water to dissolve the sample and test. The antibody used in FTS is very selective for fentanyl at high dilutions, a characteristic of the traditional use of urine testing. These street sample preparation methods can lead to mg/mL concentrations of several potential interferents. We tested whether these concentrated samples could cause false positive results on a FTS.. 20 ng/mL Rapid Response FTS were obtained from BTNX Inc. and tested against 4 different pharmaceuticals (diphenhydramine, alprazolam, gabapentin, and naloxone buprenorphine) and 3 illicit stimulants [cocaine HCl, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA)] in concentrations from 20 to 0.2 mg/mL. The FTS testing pad is divided into 2 sections: the control area and the test area. Control and test area signal intensities were quantified by ImageJ from photographs of the test strips and compared to a threshold set by fentanyl at the FTS limit of detection.. False positive results indicating the presence of fentanyl were obtained from samples of methamphetamine, MDMA, and diphenhydramine at concentrations at or above 1 mg/mL. Diphenhydramine is a common cutting agent in heroin. The street sample preparation protocols for FTS use suggested by many online resources would produce such concentrations of these materials. Street samples need to be diluted more significantly to avoid interference from potential cutting agents and stimulants.. Fentanyl test strips are commercially available, successful at detecting fentanyl to the specified limit of detection and can be a valuable tool for harm reduction efforts. Users should be aware that when drugs and adulterants are in high concentrations, FTS can give a false positive result.

Topics: Analgesics, Opioid; Drug Contamination; Drug Overdose; False Positive Reactions; Fentanyl; Heroin; Humans; Illicit Drugs; Opioid-Related Disorders

Topics: Adolescent; Adult; Analgesics, Opioid; Cannabis; Child; Cohort Studies; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Young Adult

Research on quality of life (QoL) of chronically ill patients provides an opportunity to evaluate the efficacy of long-term treatments. Although it is established that opioid replacement therapy is an effective treatment for opioid-dependent patients, there is little knowledge about physical and psychological functioning of QoL for different treatment options.. Altogether, 248 opioid-dependent patients receiving substitution treatment with either methadone/levomethadone (n = 126), diamorphine (n = 85), or buprenorphine (n = 37) were recruited in 6 German therapy centers.. Sociodemographic data were collected. QoL - physical and psychological functioning - for different substitutes was assessed using the Profile of the Quality of Life in the Chronically Ill (PLC) questionnaire.. Patient groups were similar regarding age and duration of opioid dependence. Employment rate was significantly higher (p < 0.005, φ = 0.22) in the buprenorphine group (46%) compared to methadone (18%). Dosage adjustments were more frequent (p < 0.001, φ = 0.29) in diamorphine (55%) than in methadone (30%) or buprenorphine (19%) patients. Buprenorphine and diamorphine patients rated their physical functioning substantially higher than methadone patients (p < 0.001, η2 = 0.141). Diamorphine patients reported a higher psychological functioning (p < 0.001, η2 = 0.078) and overall life improvement (p < 0.001, η2 = 0.060) compared to methadone, but not compared to buprenorphine patients (both p > 0.25).. Measurement of important QoL aspects indicates significant differences for physical and psychological functioning in patients receiving the substitutes methadone/levomethadone, diamorphine, and buprenorphine. This could be relevant for the differential therapy of opioid addiction.

Topics: Buprenorphine; Cross-Sectional Studies; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

Initiation of non-medical prescription opioid use (NMPO) during early adolescence is tightly linked to heroin and other drug use disorders and related sequelae in later adolescence and young adulthood. Few studies explore stakeholders' perspectives on the burden and determinants of youth opioid use and barriers and facilitators to engaging youth in opioid use prevention and treatment services in urban settings with longstanding opioid epidemics. In-depth interviews were conducted with 22 stakeholders representing health and social service agencies in Baltimore, Maryland from May 2018- February 2019, to examine their perspectives on the burden and context of adolescent opioid use and identify barriers and facilitators to preventing and responding to adolescent opioid use. Transcripts were analyzed using the constant comparison method to identify themes. Most respondents described a recent uptick in opioid use independently, and in combination with other substances. As compared to heroin, NMPO was perceived to be more frequently used and less stigmatized among youth. Stakeholders perceived the process of transitioning from using NMPO to heroin as more common among White vs. Black youth and was perceived as occurring faster among White vs. Black youth. Some stakeholders believed racial differences in internal stigma against heroin use, and differential health service use among Black youth and White youth may have influenced these differences. Trauma and poverty were noted determinants of youth opioid use. Barriers to service provision included youth cognitive development, stigma and structural factors (e.g., disinvestment, lack of youth-centered and integrated services). Stakeholders perceive prevalent NMPO among Baltimore youth and identify multilevel barriers to delivering prevention, treatment and harm reduction services to this population. These findings encourage further investigation of determinants and consequences of opioid use among diverse racial/ethnic groups of youth in urban settings, and development of multilevel, youth-driven and youth-centered approaches to prevention and treatment.

Topics: Adolescent; Adult; Analgesics, Opioid; Baltimore; Black or African American; Heroin; Humans; Opioid-Related Disorders; Young Adult

Canada is currently in the midst of an overdose crisis. With new and innovative approaches desperately needed, injectable opioid agonist treatment (iOAT) should be considered as an integral treatment option to prevent even more fatalities. These programs provide injectable diacetylmorphine or hydromorphone to clients with severe opioid use disorders. Currently, they remain an under-executed and under-studied treatment modality. To better understand why this may be, we performed an evolutionary concept analysis as described by Rodgers. The attributes, antecedents, consequences, and surrogate terms of iOAT were unpacked and explored. Further, four themes were identified within the literature: (1) physical and mental health, (2) illicit drug use, (3) criminal behavior, and (4) ethical considerations. Recommendations surrounding the need for additional studies that focus on the perspectives of people who use opioids (PWUO), the necessity of nursing advocacy in iOAT, and the consideration of a changing illicit drug supply were explored. Further, theoretical analysis coupled with direct input from PWUO was discussed as a necessity to move forward with iOAT.

Topics: Administration, Intravenous; Analgesics, Opioid; Canada; Harm Reduction; Heroin; Humans; Hydromorphone; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders

Unintentional overdose deaths related to opioids and psychostimulants have increased in prevalence due to the adulteration of these drugs with fentanyl. Synergistic effects between illicit compounds and fentanyl cause aggravated respiratory depression, leading to inadvertent fatalities. Traditional small-molecule therapies implemented in the expanding opioid epidemic present numerous problems since they interact with the same opioid receptors in the brain as the abused drugs. In this study, we report an optimized dual hapten for use as an immunopharmacotherapeutic tool in order to develop antibodies capable of binding to fentanyl-contaminated heroin in the periphery, thus impeding the drugs' psychoactive effects on the central nervous system. This vaccine produced antibodies with nanomolar affinities and effectively blocked opioid analgesic effects elicited by adulterated heroin. These findings provide further insight into the development of chemically contiguous haptens for broad-spectrum immunopharmacotherapies against opioid use disorders.

Topics: Animals; Drug Contamination; Drug Overdose; Fentanyl; Haptens; Heroin; Humans; Mice; Opioid-Related Disorders; Vaccines

Fentanyl and other highly potent synthetic opioids are the leading cause of opioid overdose deaths in the United States.. This study was an open-label, uncontrolled 12-week outpatient clinical trial to test the feasibility of a single-day induction onto extended-release buprenorphine (BXR) injection treatment for five adults (N = 5) with opioid use disorder using heroin-containing fentanyl. Participants were planned to receive three monthly BXR injections (300, 300, and 100 mg).. After receiving 24 mg sublingual buprenorphine (SL-BUP), all five participants received the BXR 300 mg injection on the first day of induction. All five participants were retained for the full 3-month study period postinduction and received all three scheduled BXR injections.. This study provides preliminary evidence supporting the feasibility of inducting users of heroin-containing fentanyl onto BXR 300 mg in a single day.. The ability to administer a long-acting injection of BXR that assures therapeutic serum levels for a month on the first day of treatment contact is a promising development for the treatment of OUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Fentanyl; Heroin; Humans; Narcotic Antagonists; Opioid-Related Disorders; United States

Patients with opioid use disorder experience high rates of relapse during recovery, despite successful completion of rehabilitation programs. A key factor contributing to this problem is the long-lasting nature of drug-seeking behavior associated with opioid use. We modeled this behavior in a rat drug self-administration paradigm in which drug-seeking is higher after extended abstinence than during the acute abstinence phase. The goal of this study was to determine the contribution of discrete or discriminative drug cues and drug dosage to time-dependent increases in drug-seeking. We examined heroin-seeking after 2 or 21 days of abstinence from two different self-administration cue-context environments using high or low doses of heroin and matched animals for their drug intake history. When lower dosages of heroin are used in discriminative or discrete cue protocols, drug intake history contributed to drug-seeking after abstinence, regardless of abstinence length. Incubation of opioid craving at higher dosages paired with discrete drug cues was not dependent on drug intake. Thus, interactions between drug cues and drug dosage uniquely determined conditions permissible for incubation of heroin craving. Understanding factors that contribute to long-lasting opioid-seeking can provide essential insight into environmental stimuli and drug-taking patterns that promote relapse after periods of successful abstinence.

Topics: Animals; Craving; Cues; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Heroin; Male; Opioid-Related Disorders; Rats, Sprague-Dawley; Recurrence; Self Administration; Substance Withdrawal Syndrome

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

Illicit drug use contributes to substantial morbidity and mortality. Drug scheduling, a legal measure in drug enforcement, is often structured as a hierarchy based on addiction tendency, abuse trends, and harm, but may lack data-driven evidence when classifying substances. Our study aims to measure addiction tendency and use trends based on real-world data. We used the open access database of National Police Agency, Ministry of the Interior in Taiwan and analyzed all daily criminal cases of illicit drugs from 2013 to 2017 and monthly illicit drug enforcement data from the same database from 2002 to 2017. We hypothesized that repeat and frequent use despite legal consequence may be a reflection of addictive behavior, and empirical mode decomposition was applied in analysis to calculate addiction tendency indices and intrinsic 15-year use trends. Our analysis showed heroin has the highest addiction index, followed by methamphetamine. 3,4-Methyl enedioxy methamphetamine, marijuana, and ketamine had lower addictive propensities. This result is consistent with most drug scheduling hierarchies. 15-year use trends of substances were consistent with previous epidemiological studies.

Topics: Amphetamine-Related Disorders; Anesthetics, Dissociative; Cannabis; Central Nervous System Stimulants; Crime; Databases, Factual; Hallucinogens; Heroin; Humans; Illicit Drugs; Ketamine; Marijuana Abuse; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Opioid-Related Disorders; Psychiatric Status Rating Scales; Substance-Related Disorders; Taiwan

Opioid-related deaths have increased in Western countries over recent decades. Despite numerous studies investigating opioid-related mortality, only a few have focused on the lives of the deceased individuals prior to their deaths, specifically regarding contact with care-providing authorities such as health, social and correctional services. Furthermore, a change has been noted in the last two decades as to which opioids cause most deaths, from heroin to prescription opioids. However, studies comparing fatalities caused by different substances are rare. The aim of this study was to investigate contact with care-providing authorities during the year prior to death among individuals who died as a result of opioid intoxication and to analyse differences relating to which opioids caused their deaths.. The study is based on retrospective register data and includes 180 individuals with a history of illicit drug use, who died from opioid intoxication in Skåne, Sweden, between 1 January 2012 to 31 December 2013 and 1 July 2014 to 30 June 2016. Intoxications caused by heroin, methadone, buprenorphine and fentanyl were included. Data were collected from the National Board of Forensic Medicine, regional health care services, municipal social services and the Prison and Probation Service. Statistical testing was performed using Pearson's chi-square test, Fisher's exact test and the Mann-Whitney U test to analyse group differences.. A total of 89% of the deceased individuals had been in contact with one or more of the care-providing authorities during the year prior to death; 75% had been in contact with health care, 69% with the social services, 28% with the Prison and Probation Service, and 23% had been enrolled in opioid substitution treatment at some point during their final year of life. Few differences appeared between the substance groups with regard to which opioid contributed to the death. In addition to opioids, sedatives were present in more than 80% of the cases. Individuals whose deaths were buprenorphine-related had been in contact with the social services to a significantly lesser extent during the year prior to death.. The studied population is characterised by extensive contact with care-providing authorities, thus providing numerous opportunities for authorities to reach this group with preventive and other interventions. Few differences emerged between groups with regard to which opioid had contributed to the death.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Female; Fentanyl; Heroin; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Registries; Retrospective Studies; Sweden

Injectable opioid agonist treatment (iOAT) was designed as a pragmatic and compassionate approach for people who have not benefitted from medication assisted treatment with oral opioids (e.g., methadone). While, a substantial body of clinical trial evidence has demonstrated the safety and effectiveness of iOAT, considerably less is known about the patient-centered aspects of this treatment and their role in self-reported treatment goals and outcomes. The aim of this study was to explore participants' experiences in iOAT as they broadly relate to the domains of patient-centered care. A secondary goal was to explore how these experiences affected participants' self-reported treatment outcomes.. A qualitative methodology, and constructivist grounded theory approach, was used to guide sampling, data collection and analysis. A total of 30 in-depth interviews were conducted with people receiving iOAT in North America's first clinic. Audio-recordings for each semi-structured interview were transcribed and read repeatedly. The strategy of constant comparison was used through iterative stages of line-by-line, focused and theoretical coding until theoretical saturation was achieved.. "Building healthcare provider relationships for patient-centered care in iOAT" was the emergent core concept. Healthcare provider relationships were established through two interrelated processes: 'Opening up' was attributed to the positive environment, and to feeling understood and supported by healthcare providers. 'Being a part of care' emerged as participants felt safe to ask for what was needed and had opportunities to collaborate in treatment decisions. These processes established a foundation in which participants experienced care that was responsive to their individual dose, health and psychosocial needs.. The core concept suggested that therapeutic relationships were fundamental to experiences of patient-centered care in iOAT. When relationships were respectful and understanding, participants received individualized and holistic care in iOAT. These findings offer a valuable example of how therapeutic relationships can be strengthened in other substance use treatment settings, particularly when responding to the diverse treatment needs of clients.

Topics: Administration, Intravenous; Adult; Attitude of Health Personnel; Female; Grounded Theory; Health Personnel; Health Status; Heroin; Humans; Hydromorphone; Interviews as Topic; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Patient-Centered Care; Professional-Patient Relations; Qualitative Research

Heavy metals, including thallium and lead, are introduced to illicit drug users' body as a result of using drugs such as cocaine and heroin.. This study aimed to determine urine, blood, and hair thallium (Tl) concentrations in illicit opioid users along with the relevant clinical signs and symptoms consistent with thallotoxicosis and to compare them with the corresponding variables in the control non-opioid user group.. This case-control study was conducted on 50 illicit opioid users who had abused opioids continuously for more than a year, referred to Amirie Drug Abuse Treatment Clinic in Kashan, Iran. The control group included 50 non-opioid users. Thallium concentrations in urine, blood, and hair were assessed in both groups (. In the studied group, the median (interquartile range) concentrations of thallium in urine, blood, and hair were 54.8 ± 79.9 μg/L, 14.5 ± 11.1 μg/L, and 5.4 ± 3.7 µg/g, respectively; these values were 4.8 ± 5.2 μg/L, 2.5 ± 2.4 μg/L, and 1.4 ± 1.1 µg/g, respectively, in the control group. There were significant differences in urine, blood, and hair thallium concentrations between the study group and the control group (. The results of the study showed that thallium concentrations in urine, blood, and hair in illicit opioid users were significantly higher than the comparable concentrations in the control group. This can be due to the use of illicit opioids adulterated with thallium. Also, this study showed long-term illicit opioid use may lead to thallium exposure. In addition, cigarette smoking was associated with increased thallium exposure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Case-Control Studies; Female; Hair; Heroin; Humans; Illicit Drugs; Iran; Male; Middle Aged; Opioid-Related Disorders; Opium; Thallium; Young Adult

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

Opioid overdose mortality continues to increase in the United States despite significant investments to reverse the epidemic. The national response to-date has focused primarily on reducing opioid prescribing, yet reductions in prescribing have been associated with patients reporting uncontrolled pain, psychological distress, and transition to illicit substances. The aim of this study is to qualitatively explore chronic pain management experiences among PLWH with a history of illicit substance use after long-term opioid therapy reductions or discontinuations.. We analyzed 18 interviews, stopping upon reaching thematic saturation, with HIV-positive participants with a history of substance use who were enrolled in a longitudinal cohort study to assess the impact of prescribing changes among patients with chronic pain. Participants in this nested qualitative study had been reduced/discontinued from opioid pain relievers (OPRs) within the 12 months prior to interview. Interviews were audio-recorded and transcribed verbatim. Two analysts coded all interviews, interrater reliability was measured, and coding discrepancies discussed. The study took place in San Francisco, California in 2018.. Eleven participants were male with a mean age of 55; 8 were African American and 8 were White. All participants were HIV-positive, actively engaged in primary care, and had a lifetime history of illicit substance use. Twelve reported using illicit substances within the past year, including non-prescription opioids/heroin (10), and stimulant use (10). After being reduced/discontinued from their long-term opioid therapy, patients reported developing complex multimodal pain management systems that often included both nonpharmacological approaches and illicit substance use. Participants encountered a range of barriers to nonpharmacological therapies including issues related to accessibility and availability. Participants often reported attempts to replicate their prior OPR prescription by seeking out the same medication and dose from illicit sources and reported transitioning to heroin after exhausting other options.. After being reduced/discontinued from OPRs, HIV-positive patients with a history of substance use reported experimenting with a range of pain management modalities including nonpharmacological therapies and illicit substance use to manage symptoms of opioid withdrawal and pain. Providers should consider that any change to a patients' long-term opioid therapy may result in experimentation with pain management outside of the medical setting and may want to employ patient-centered, holistic approaches when managing patients' opioid prescriptions and chronic pain.

Topics: Acupuncture; Analgesics, Opioid; Drug Prescriptions; Female; Heroin; HIV Infections; Humans; Male; Middle Aged; Opioid-Related Disorders; Pain; Pain Management; San Francisco; Transgender Persons

The increased availability of prescription opioids (PO) and non-medical prescription opioids (NMPO) has fundamentally altered drug markets and typical trajectories from initiation to high-risk use among people who use opioids (PWUO). This multi-site study explores trends in opioid initiation in three US cities and associations with sociodemographic factors, current drug use and overdose risk.. We analysed survey data from a cross-sectional study of PWUO in Baltimore, Maryland (n = 173), Boston, Massachusetts (n = 80) and Providence, Rhode Island (n = 75). Age of first exposure to PO, NMPO and heroin was used to calculate opioid of initiation, and multinomial regression was employed to explore correlates of initiating with each.. Thirty-three percent of PWUO initiated with heroin, 24% with PO, 18% with NMPO and 24% with multiple opioids in their first year of use. We observed a reduction in heroin initiation and gradual replacement with PO/NMPO over time. Women were more likely to initiate with NMPO [relative risk ratio (RRR) 2.4; 95% confidence interval (CI) 1.1, 5.0], PO (RRR 2.2, 95% CI 1.1, 4.4) or multiple opioids (RRR 2.1, 95% CI 1.1, 4.2), than heroin. PWUO initiating with NMPO had significantly higher current benzodiazepine use, relative to those initiating with heroin (RRR 3.2, 95% CI 1.4, 7.4), and a high prevalence of current fentanyl use (30%).. Our study highlights women and PWUO initiating with NMPO as key risk groups amid the changing landscape of opioid use and overdose, and discusses implications for targeted prevention and treatment.

Topics: Adult; Analgesics, Opioid; Baltimore; Boston; Cities; Cross-Sectional Studies; Female; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Rhode Island; Sex Distribution; Substance-Related Disorders

This paper includes the voices of people who are members of a peer-led drug user group (SNAP) in Canada who are receiving heroin-assisted treatment (HAT) outside of a clinical trial. Drawing from critical drug studies, we problematize the criteria for severe opioid use disorder (OUD) from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, by exploring SNAP members' experiences in relation to heroin-assisted treatment, and examining how SNAP participants' narratives challenge conventional notions of what constitutes severe opioid use disorder.. Drawing on critical analysis and research guidelines developed by drug user unions and organizations, and critical methodological frameworks on ethical community-based-and-responsive research for social justice, in this paper we focus on semi-structured interviews conducted with 36 SNAP members at the Vancouver Area Network of Drug Users site in the Downtown Eastside of Vancouver, Canada. We included opened ended questions about experiences prior to receiving HAT, experiences while receiving HAT, experiences of drug use and cessation, and future hopes.. Although SNAP participants were diagnosed as suffering from OUD, the DSM-5 criteria for OUD fails to encompass their diverse experiences of opioid use. Nor does the DSM diagnosis capture the complexities of their lived experience. The DSM OUD constructs an idea of addiction and the addicted person based on a list of symptoms thought to be associated with extended use of opioids. The problem with this is that many of these "symptoms" of drug use are, in the case of SNAP participants, tied to contextual issues of living in the DTES, experiencing structural vulnerability, and being the target of punitive drug policies and laws.. To label someone as having a severe disorder shifts the focus from political and social issues, including the lived experiences of people who use heroin. The DSM-5 de-contextualizes drug use. How addiction and heroin are constituted has political implications that will determine what types of services and programs will be set up. Treating a disorder, or a person with a disorder, requires a much different approach than understanding heroin use as a habit. SNAP, and their allies, are rupturing conventional ideas about heroin and taken for granted assumptions about people who use heroin.

Topics: Analgesics, Opioid; Canada; Diagnostic and Statistical Manual of Mental Disorders; Heroin; Humans; Opioid-Related Disorders

The purpose of this study was to describe an identified association between necrotizing enterocolitis (NEC) and prenatal opioid exposure with neonatal abstinence syndrome (NAS) in late preterm and full-term neonates.. In this single-center retrospective cohort study, we analyzed inborn neonates with the diagnosis of NEC discharged from 2012 through 2017. We compared infants with NEC > 35 weeks' gestation to those with NEC<35 weeks' gestation. We compared gestational age, birth weight, age of onset of symptoms, and incidence of prenatal drug exposure between groups. Significance was determined using Mann-Whitney and Fisher's exact tests.. Over the study period, 23 infants were identified with NEC, 9 (39%) were babies > 35 weeks at birth and 14 (61%) < 35 weeks. Those > 35 weeks had a higher birth weight, earlier onset of symptoms, and a higher percentage of prenatal exposure to opioids compared to those < 35 weeks' gestation. We further described seven infants with late gestational age onset NEC associated with prenatal opioid exposure.. In this cohort of infants with NEC discharged over a 6 year period we found a higher than expected percentage of infants born at a later gestational age. We speculate that prenatal opioid exposure might be a risk factor for NEC in neonates born at > 35 weeks.

Topics: Analgesics, Opioid; Buprenorphine; Cohort Studies; Enterocolitis, Necrotizing; Female; Fetal Blood; Gestational Age; Heroin; Humans; Infant, Newborn; Infant, Premature; Male; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies

After decades of increased opioid pain reliever prescribing, providers are rapidly reducing prescribing. We hypothesized that reduced access to prescribed opioid pain relievers among patients previously reliant upon opioid pain relievers would result in increased illicit opioid use.. We conducted a retrospective cohort study among 602 publicly insured primary care patients who had been prescribed opioids for chronic non-cancer pain for at least three consecutive months in San Francisco, recruited through convenience sampling. We conducted a historical reconstruction interview and medical chart abstraction focused on illicit substance use and opioid pain reliever prescriptions, respectively, from 2012 through the interview date in 2017-2018. We used a nested-cohort design, in which patients were classified, based on opioid pain reliever dose change, into a series of nested cohorts starting with each follow-up quarter. Using continuation-ratio models, we estimated associations between opioid prescription discontinuation or 30% increase or decrease in dose, relative to no change, and subsequent frequency of heroin and non-prescribed opioid pain reliever use, separately. Models controlled for demographics, clinical and behavioral characteristics, and past use of heroin or non-prescribed opioid pain relievers. A total of 56,372 and 56,484 participant-quarter observations were included from the 597 and 598 participants available for analyses of heroin and non-prescribed opioid pain reliever outcomes, respectively. Participants discontinued from prescribed opioids were more likely to use heroin (Adjusted Odds Ratio (AOR) = 1.57, 95% CI: 1.25-1.97) and non-prescribed opioid pain relievers (AOR = 1.75, 1.45-2.11) more frequently in subsequent quarters compared to participants with unchanged opioid prescriptions. Participants whose opioid pain reliever dose increased were more likely to use heroin more frequently (AOR = 1.67, 1.32-2.12). Results held throughout sensitivity analyses. The main limitations were the observational nature of results and limited generalizability beyond safety-net settings.. Discontinuation of prescribed opioid pain relievers was associated with more frequent non-prescribed opioid pain reliever and heroin use; increased dose was also associated with more frequent heroin use. Clinicians should be aware of these risks in determining pain management approaches.

Topics: Analgesics, Opioid; Chronic Pain; Cohort Studies; Drug Prescriptions; Female; Heroin; Humans; Illicit Drugs; Male; Middle Aged; Opioid-Related Disorders; Pain Management; Primary Health Care; Retrospective Studies; San Francisco

Since 2010, heroin-related overdoses have risen sharply, coinciding with policies to restrict access to prescription opioids. It is unknown if patients tapered or discontinued off prescription opioids transitioned to riskier heroin use. This study examined opioid prescribing, including long-term opioid therapy (LTOT) and discontinuation, prior to heroin overdose.. We used retrospective longitudinal data from a national claims database to identify adults with an emergency or inpatient claim for heroin overdose between January 2010 and June 2017. Receipt of opioid prescription, LTOT episodes, and discontinuation of LTOT were measured for the period of one year prior to heroin overdose.. We identified 3183 individuals (53.2% age 18-25; 70.0% male) with a heroin overdose (incidence rate 4.20 per 100k person years). Nearly half (42.3%) received an opioid prescription in the prior 12 months, and 10.9% had an active opioid prescription in the week prior to overdose. LTOT at any time in the 12 months prior to overdose was uncommon (12.8%) among those with heroin overdoses, especially among individuals 18-25 years old (3.5%, P < 0.001). LTOT discontinuation prior to overdose was also relatively uncommon, experienced by 6.7% of individuals aged 46 and over and 2.5% of individuals aged 18-25 years (P < 0.001).. Prior to heroin overdose, prescription opioid use was common, but LTOT discontinuation was uncommon and observed primarily in older individuals with the lowest heroin overdose rates. Further study is needed to determine if these prescribing patterns are associated with increased heroin overdose.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Databases, Factual; Drug Overdose; Drug Prescriptions; Emergency Service, Hospital; Female; Heroin; Humans; Insurance Claim Review; Insurance, Health; Longitudinal Studies; Male; Middle Aged; Opioid-Related Disorders; Practice Patterns, Physicians'; Retrospective Studies; 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

To evaluate trends related to accidental overdose deaths in Oklahoma, with a focus on opioids and methamphetamine. All accidental drug overdose deaths in the state of Oklahoma from 2002 to 2017 were reviewed. Opioids were grouped into the following categories: all opioids, prescription opioids, synthetic opioids and heroin. Age-adjusted death rates for methamphetamine and each opioid category were calculated and analyzed. Accidental overdoses accounted for 9,936 deaths during the study period. Of these, opioids were seen in 62.9%, with prescription opioids comprising 53.8%, synthetic opioids 10.3% and heroin 2.8%. Synthetic opioids, despite a recent upward nationwide trend, showed a slight overall decrease (-6.8%) from 2009 to 2017. In contrast, methamphetamine showed a 402.2% increase from 2009 to 2017 and an overall increase of 1,526.7%. Methamphetamine was involved in the most overdoses (1,963), followed by oxycodone (1,724). Opioid-related deaths were most common among white individuals (90.3%) and showed a slight male predilection (56.9%). With the intent of assessing the opioid epidemic as it relates to accidental overdoses in Oklahoma, this study suggests that opioid-related overdoses have slowed in recent years amidst a sharp increase in methamphetamine deaths.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Heroin; Humans; Male; Methamphetamine; Oklahoma; Opioid-Related Disorders; Oxycodone

Topics: Adolescent; Adult; Analgesics, Opioid; Epidemics; Female; Heroin; Humans; Male; Middle Aged; Opioid Epidemic; Opioid-Related Disorders; Risk Assessment; Risk-Taking; United States

Opioid use during pregnancy has been linked to several adverse outcomes including stillbirth, preterm birth and neonatal abstinence syndrome. Recent data suggest that heroin use has increased in the United States (US) whereas prescription opioid use has decreased. Prevalence estimates for reproductive age women combine heroin and non-medical prescription opioid use, which might mask the increasing heroin trend. The aim of the current study is to estimate the prevalence of heroin use among US women of reproductive age, stratified by pregnancy status. For each year, a representative sample of the US civilian non-institutionalized population is recruited for the National Survey on Drug Use and Health (NSDUH). Pregnancy status and heroin use were assessed in women 15-44 years of age (n = 277,333) using audio computerized-assisted self-interviews. From 2004 to 2017, the prevalence of past 30-day heroin use was 12 per 10,000 reproductive age women (95% confidence interval [CI] = 11, 14). Heroin use has increased from 6 per 10,000 women in 2004-05 to 18 per 10,000 women in 2016-17 (Average percent change = 20.8; 95% 11.2, 31.2). The increase was evident among non-pregnant women, but not among pregnant women. Heroin use remains uncommon among women of reproductive age, yet its prevalence has increased over time. Screening for heroin use might be needed at multiple time points including prior to pregnancy to mitigate adverse outcomes associated with use during pregnancy.

Topics: Female; Health Surveys; Heroin; Humans; Infant, Newborn; Opioid-Related Disorders; Pregnancy; Pregnant Women; Premature Birth; United States

Opioid misuse has reached epidemic proportions among emerging adults in the U.S. To inform prevention efforts, this study examined adolescent factors related to alcohol and marijuana (AM) use that are associated with a higher or lower risk for opioid misuse during emerging adulthood.. We used 11 waves of survey data from a diverse California cohort (N = 6,509). Predictor variables from waves 1-7 (ages 11-17) included individual (resistance self-efficacy, positive expectancies) family (older sibling and important adult use), and peer (perceived norms, time spent with peers who use, peer approval) factors. Opioid misuse at wave 8 (mean age = 18.3) and wave 11 (mean age = 21.6) included heroin and nonmedical prescription drug use.. Initial latent growth models (LGMs) indicated that nearly all intercepts and slopes for individual, family, and peer AM factors predicted opioid misuse at waves 8 and 11. These associations were reduced to non-significance after adjusting for prior other substance use with the exception of three intercepts: positive expectancies, peer approval, and older sibling use predicted a higher probability of opioid misuse at wave 8.. Stronger AM positive expectancies, perceived peer approval of AM use, and older sibling AM use during adolescence are associated with a higher likelihood of opioid misuse during the transition to emerging adulthood. However, most adolescent factors were no longer associated with subsequent opioid misuse after adjusting for history of other substance use, highlighting the importance of considering the larger context of substance use in studies of opioid misuse among young people.

Topics: Adolescent; Adolescent Behavior; Adult; Alcohol Drinking; Analgesics, Opioid; Child; Female; Heroin; Humans; Male; Marijuana Abuse; Marijuana Smoking; Opioid-Related Disorders; Peer Group; Prescription Drug Misuse; Prescription Drugs; Surveys and Questionnaires; Young Adult

Although much of the attention surrounding the opioid epidemic has focused on rural and suburban Whites and prescription opioids, heroin overdoses among urban Blacks are on the rise. While some argue that legalization of cannabis will combat the epidemic, there are concerns it ignores the shift in the epidemic and could increase vulnerability to opioid misuse. The goal of this study is to examine the association between cannabis use from adolescence to young adulthood with opioid misuse in a primarily urban Black cohort.. Data are from a study of 580 youth (87 % Black and 71 % low SES) residing in Baltimore City followed from ages 6-26. Cannabis trajectories were identified between ages 14-26 using group-based trajectory modeling. Logistic regressions were conducted to examine the impact of trajectories on opioid misuse in young adulthood adjusting for individual, neighborhood and peer factors. Opioid misuse was defined as using heroin or narcotics or painkillers without a prescription between ages 19-26.. Four cannabis trajectories were identified: Low/Non-Users (59.7 %), Adolescent Onset Limited (19.5 %), Young Adult Onset (10.8 %), and Adolescent Onset Chronic (10.0 %). Adolescent Onset Chronic cannabis users had the highest rate of opioid misuse (44.8 %) followed by Adolescent Onset Limited (18.8 %), Young Adult Onset (14.8 %) and Low/Non-Users (8.3 %). Prevalences were significantly higher for Adolescent Onset groups relative to Low/Non-Users even after adjustment for individual, neighborhood and peer factors.. Adolescent onset cannabis use is associated with opioid misuse in young adulthood among urban Blacks even after adjustment for socioecological factors associated with opioid misuse.

Topics: Adolescent; Adult; Analgesics, Opioid; Black or African American; Cannabis; Child; Cohort Studies; Drug Overdose; Female; Heroin; Humans; Male; Marijuana Smoking; Motivation; Opioid-Related Disorders; Peer Group; Prescription Drug Misuse; Residence Characteristics; Young Adult

Overdose deaths from synthetic opioids (e.g., fentanyl) increased 10-fold in the United States from 2013 to 2018, despite such opioids being rare in illicit drug markets west of the Mississippi River. Public health professionals have feared a "fentanyl breakthrough" in western U.S. drug markets could further accelerate overdose mortality. We evaluated the number and nature of western U.S. fentanyl deaths using the most recent data available.. We systematically searched jurisdictions west of the Mississippi River for publicly available data on fentanyl-related deaths since 2018, the most recent Centers for Disease Control and Prevention (CDC) statistics. Using mortality data from 2019 and 2020, we identified changes in fentanyl-related mortality rate and proportion of fatal heroin-, stimulant, and prescription pill overdoses involving fentanyl.. Seven jurisdictions had publicly available fentanyl death data through December 2019 or later: Arizona; California; Denver County, CO; Harris County, TX; King County, WA; Los Angeles County, CA; and Dallas-Fort Worth, TX (Denton, Johnson, Parker, and Tarrant counties). All reported increased fentanyl deaths over the study period. Their collective contribution to national synthetic narcotics mortality increased 371 % from 2017 to 2019. Available 2020 data shows a 63 % growth in fentanyl-mortality over 2019. Fentanyl-involvement in heroin, stimulant, and prescription pill deaths has substantially grown.. Fentanyl has spread westward, increasing deaths in the short-term and threatening to dramatically worsen the nation's already severe opioid epidemic in the long-term. Increasing the standard dose of naloxone, expanding Medicaid, improving coverage of addiction treatment, and public health educational campaigns should be prioritized.

Topics: Analgesics, Opioid; Drug Overdose; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Local Government; Longitudinal Studies; Male; Opioid-Related Disorders; Population Surveillance; State Government; United States

Corrections-involved adults with a history of opioid use disorder are at elevated risk of opioid overdose following release from correctional settings. Increased opioid prescribing restrictions and monitoring during a time when heroin is becoming cheaper and ubiquitous means that adults who misused prescription opioids prior to incarceration may be reentering communities at greater risk for heroin exposure and use.. Determine risk factors of post-release heroin use among a sample of adults who participated in corrections-based drug treatment in Kentucky released between 2012 and 2017.. Survey data obtained as part of an ongoing evaluation of corrections-based drug treatment were examined.. The final sample (N = 1,563) was majority male (80.9%). Nearly 11.0% reported past-year heroin use following their release. Depressive symptoms, polydrug use, and urban proximity were more common among participants reporting post-release heroin use. Heroin use 30 days prior to incarceration was associated with a 432.1% increase in odds of heroin use subsequent to incarceration. Post-release suicidal ideation increased odds of heroin use by 154.2%, whereas reporting satisfaction from social interactions decreased odds of use by nearly 60%. Post-release use of cocaine and diverted buprenorphine were associated with increased likelihood of heroin use during this time period, increasing odds by 469.1% and 265.9%, respectively. Residing in Central Appalachia subsequent to incarceration was associated with decreased likelihood of use.. In this sample, post-release heroin use was associated with concerning features, such as polydrug use, lack of social satisfaction, and suicidal ideation. These features can serve as clear targets for clinical intervention.

Topics: Adult; Appalachian Region; Female; Heroin; Humans; Jails; Kentucky; Longitudinal Studies; Male; Middle Aged; Opioid-Related Disorders; Practice Patterns, Physicians'; Prisoners; Prisons; Risk Factors; Suicidal Ideation

Relapse into drug use is a major problem faced by recovering addicts. In humans, an intensification of the desire for the drug induced by environmental cues-incubation of drug craving-has been observed. In rodents, this phenomenon has been modeled by studying drug seeking under extinction after different times of drug withdrawal (or using a natural reinforcer). Although much progress has been made, an integrated approach simultaneously studying different drug classes and natural reward and examining different brain regions is lacking. Lewis rats were used to study the effects of cocaine, heroin, and sucrose seeking incubation on six key brain regions: the nucleus accumbens shell/core, central/basolateral amygdala, and dorsomedial/ventromedial prefrontal cortex. We analyzed PSD95 and gephyrin protein levels, gene expression of glutamatergic, GABAergic and endocannabinoid elements, and amino acid transmitter levels. The relationships between the areas studied were examined by Structural Equation Modelling. Pathways from medial prefrontal cortex and basolateral complex of the amygdala to central nucleus of the amygdala, but not to the nucleus accumbens, were identified as common elements involved in the incubation phenomenon for different substances. These results suggest a key role for the central nucleus of amygdala and its cortical and amygdalar afferences in the incubation phenomenon, and we suggest that by virtue of its regulatory effects on glutamatergic and GABAergic dynamics within amygdalar circuits, the endocannabinoid system might be a potential target to develop medications that are effective in the context of relapse.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Central Amygdaloid Nucleus; Cocaine; Cocaine-Related Disorders; Disease Models, Animal; Dopamine Uptake Inhibitors; Heroin; Male; Opioid-Related Disorders; Rats; Rats, Inbred Lew; Reinforcement, Psychology; Self Administration; Sucrose

The Toll-like receptor 4 (TLR4) antagonists, (+)-naloxone and (+)-naltrexone, have been reported to decrease self-administration of opioids in rats and to reduce other preclinical indicators of abuse potential. However, under the self-administration conditions studied, the effects of TLR4 antagonists were not reinforcer selective, questioning the involvement of those receptors and their mediated inflammatory response specifically in opioid abuse. The objectives of the current study were to further characterize the reinforcer specificity of TLR4 antagonism in opioid self-administration and to explore its effects in a preclinical model of craving/relapse. The TLR4 antagonist (+)-naltrexone decreased responding in rats trained to self-administer the µ-opioid receptor agonist remifentanil, but with a potency that was not significantly different from that observed in another group of subjects in which responding was maintained by food reinforcement. Responding reinstated by heroin injection was decreased by (+)-naltrexone; however, a similar reduction was not reproduced with the administration of another TLR4 antagonist, lipopolysaccharide from Rhodobacter sphaeroides, administered into the NAcc shell. Thus, TLR4 antagonists lacked reinforcer selectivity in reducing opioid self-administration and were not uniformly effective in a model of craving/relapse, suggesting limitations on the development of (+)-naltrexone or TLR4 antagonists as treatments for opioid abuse.

Topics: Analgesics, Opioid; Animals; Conditioning, Operant; Heroin; Male; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Toll-Like Receptor 4

We have previously demonstrated that heroin's first metabolite, 6-acetylmorphine (6-AM), is an important mediator of heroin's acute effects. However, the significance of 6-AM to the rewarding properties of heroin still remains unknown. The present study therefore aimed to examine the contribution of 6-AM to heroin-induced reward and locomotor sensitization. Mice were tested for conditioned place preference (CPP) induced by equimolar doses of heroin or 6-AM (1.25-5 μmol/kg). Psychomotor activity was recorded during the CPP conditioning sessions for assessment of drug-induced locomotor sensitization. The contribution of 6-AM to heroin reward and locomotor sensitization was further examined by pretreating mice with a 6-AM specific antibody (anti-6-AM mAb) 24 hours prior to the CPP procedure. Both heroin and 6-AM induced CPP in mice, but heroin generated twice as high CPP scores compared with 6-AM. Locomotor sensitization was expressed after repeated exposure to 2.5 and 5 μmol/kg heroin or 6-AM, but not after 1.25 μmol/kg, and we found no correlation between the expression of CPP and the magnitude of locomotor sensitization for either opioid. Pretreatment with anti-6-AM mAb suppressed both heroin-induced and 6-AM-induced CPP and locomotor sensitization. These findings provide evidence that 6-AM is essential for the rewarding and sensitizing properties of heroin; however, heroin caused stronger reward compared with 6-AM. This may be explained by the higher lipophilicity of heroin, providing more efficient drug transfer to the brain, ensuring rapid increase in the brain 6-AM concentration.

Topics: Analgesics, Opioid; Animals; Brain; Conditioning, Psychological; Disease Models, Animal; Heroin; Locomotion; Male; Mice; Mice, Inbred C57BL; Morphine Derivatives; Opioid-Related Disorders; Reward

Topics: Curriculum; Drug Overdose; Education, Medical, Undergraduate; Evidence-Based Practice; Fatal Outcome; Heroin; Humans; Male; Opioid-Related Disorders; Recurrence; Students, Medical; Suicide

Persistent transcriptional and morphological events in the nucleus accumbens (NAc) and other brain reward regions contribute to the long-lasting behavioral adaptations that characterize drug addiction. Opiate exposure reduces the density of dendritic spines on medium spiny neurons of the NAc; however, the underlying transcriptional and cellular events mediating this remain unknown. We show that heroin self-administration negatively regulates the actin-binding protein drebrin in the NAc. Using virus-mediated gene transfer, we show that drebrin overexpression in the NAc is sufficient to decrease drug seeking and increase dendritic spine density, whereas drebrin knockdown potentiates these effects. We demonstrate that drebrin is transcriptionally repressed by the histone modifier HDAC2, which is relieved by pharmacological inhibition of histone deacetylases. Importantly, we demonstrate that heroin-induced adaptations occur only in the D1

Topics: Animals; Behavior, Animal; Epigenesis, Genetic; Heroin; Histone Deacetylase 2; Male; Microfilament Proteins; Neuronal Plasticity; Neurons; Neuropeptides; Nucleus Accumbens; Opiate Alkaloids; Opioid-Related Disorders; Pain; Rats, Sprague-Dawley; Synapses

Assess relationships among non-medical use of prescription opioid analgesics (POAs), heroin use, and HIV and hepatitis C (HCV) infection among persons who inject drugs (PWID) in New York City, 2016-2018.. PWID (N = 134) were recruited from Mount Sinai Beth Israel drug treatment programs. HIV seropositive persons were oversampled. A questionnaire was administered, and serum samples were collected for HIV and HCV testing. Analyses were stratified by HIV serostatus and compared those who had used POAs to those who had not used POAs.. Among the participants, 97% reported injecting heroin, 44% reported injecting cocaine, and 47% reported smoking crack cocaine in the 6 months prior to the interview. There were 66% who reported oral non-medical use of POAs, with 42% using oral POAs in the previous 6 months. There was a clear historical pattern in median year of first injection for different groups: HIV seropositive persons (1985), HIV seronegative persons who never used POAs (1999), and HIV seronegative persons who used POAs (2009). By the time of interview (2016-2018), however, almost all participants (97%) reported injecting heroin. All PWID who reported using POAs also reported injecting heroin.. Non-medical POA use among PWID was very common and should not be considered a separate drug use epidemic, but as an additional component of the continuing heroin/poly-drug use epidemic, itself a part of the syndemic of opioid use, stimulant use, overdose, HCV and HIV occurring in New York City.

Topics: Adult; Analgesics, Opioid; Female; Hepatitis C; Heroin; HIV Infections; Humans; Male; Middle Aged; New York City; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance-Related Disorders; Young Adult

Fentanyl has become widespread in the illicit opioid supply, and is a major driver of overdose mortality.. This study used a medical records review at a community opioid use disorder treatment program to examine patient-level correlates of fentanyl exposure as measured by urine testing at admission (N= 1,174). Additionally, an anonymous survey was conducted with 114 patients about their experiences and preferences regarding fentanyl.. Overall, 39% of patients entering treatment tested positive for fentanyl. Prevalence of fentanyl exposure differed based on other drug test results (fentanyl-positive = 81.1% vs. 15.4% among participants positive vs. negative for heroin/opioids, p < .001; 59.0% vs. 38.3% among participants positive vs. negative for methadone, p = .001; 53.8% vs. 24.9% among participants positive vs. negative for cocaine, p < .001), prior addiction treatment (40.6% vs. 32.0% among participants with vs. without prior treatment, p < .05), and mental health (36.7% vs. 43.1% among participants with vs. without co-occurring psychiatric diagnosis, p < .05). Most participants reported knowingly using fentanyl (56.1%) and knowing people who prefer fentanyl as a drug of choice (65.8%). Preference for fentanyl (alone or mixed with heroin) was expressed by 44.7% of participants. Participants thought fentanyl withdrawal had faster onset (53.5%), greater severity (74.8%), and longer duration (62.0%) than heroin withdrawal.. Recent opioid and cocaine use were strongly associated with fentanyl exposure in this sample. Although fentanyl exposure is often unintentional, there may be a subgroup of individuals who come to prefer fentanyl. Future research should examine the relationship between fentanyl use, patient preferences for fentanyl, and treatment outcomes.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Overdose; Female; Fentanyl; Heroin; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Surveys and Questionnaires; Treatment Outcome

Topics: Analgesics, Opioid; Canada; Heroin; Humans; Hydromorphone; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; Opiate Substitution Treatment; Opioid-Related Disorders; Self Administration

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

Buprenorphine/naloxone treatment is a highly effective treatment for opioid use disorder decreasing illicit opioid use and both all-cause and opioid-involved overdose mortality. The purpose of this study was to investigate the relationships between buprenorphine/naloxone prescribing and high-dose opioid analgesic prescribing (HDOAP) over time.. This longitudinal study used 2012-2017 Kentucky All Schedule Prescription Electronic Reporting data and cross-lagged structural equation analysis. For each quarter-county observation, HDOAP rate (per 1,000 residents with opioid analgesic prescriptions) was used to predict buprenorphine/naloxone prescribing rate at the next quarter, and simultaneously buprenorphine/naloxone prescribing rate was used to predict HDOAP at the next quarter, accounting for baseline socioeconomic status, medical needs for opioid analgesics, and heroin availability.. On average, HDOAP rates in Kentucky decreased by more than 10% (p < .0001) and buprenorphine/naloxone prescribing rates increased by more than 5% (p < .0001) per quarter over the study period. Every one-per-thousand higher HDOAP rate in an earlier quarter was associated with a 0.01/1,000 increase in the buprenorphine/naloxone prescribing rate in a later quarter (p = .009). Conversely, a one-unit higher buprenorphine/naloxone prescribing rate in an earlier quarter was associated with a 0.01/1,000 reduction in the HDOAP rate in a subsequent quarter (p = .017).. Our results indicate a significant reciprocal relationship between HDOAP and buprenorphine/naloxone prescribing and a clinically meaningful effect of buprenorphine/naloxone prescribing on reducing HDOAP. Future studies on buprenorphine/naloxone treatment expansion should take into account this bi-directional association in the context of longitudinal data and evaluate for public health benefits beyond the reduction of HDOAP.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Drug Prescriptions; Female; Heroin; Humans; Kentucky; Latent Class Analysis; Longitudinal Studies; Male; Opiate Substitution Treatment; Opioid-Related Disorders

Prior studies in heroin use disorder reported low rates (10%) of suicidal intention with non-fatal opioid overdose but did not assess dimensional ratings of suicidal ideation. This study aims to quantify the frequency and intensity of ratings of desire to die and perceived overdose risk proximal to the most recent opioid overdose event among individuals admitted for opioid use disorder detoxification/stabilization.. Cross-sectional study (June 2017-July 2018) assessing patterns of opioid use and variables related to overdose history was conducted in a not-for-profit psychiatric hospital. Adults (>18 years) with opioid use disorder were eligible and 120 of 122 participants completed all measures. Forty-one percent were women and 85% self-identified as white. Participants' perceptions of the likelihood of overdose and their suicidal motivations (defined as desire to die) prior to most recent opioid overdose was self-rated on a scale of 0 (no desire to die/no risk of death) to 10 (I definitely wanted to die/I definitely thought I would die).. Most (92%) surviving opioid overdose used heroin/fentanyl; over half reported some desire to die prior to their most recent overdose, with 36% reporting strong (>7/10) desire to die and 21% reporting 10/10 "I definitely wanted to die." Perceptions of overdose risk were also variable, with 30% reporting no (0/10) likelihood of overdose and 13% reporting a high (10/10) likelihood.. Suicidal motivation prior to opioid overdose is common and falls along a continuum of severity. Longitudinal studies are needed to determine if suicide prevention interventions may reduce opioid overdose in those at risk.

Topics: Adult; Cross-Sectional Studies; Drug Overdose; Female; Fentanyl; Heroin; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Motivation; Opioid-Related Disorders; Self Report; Suicidal Ideation; Survivors; 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

Rates of overdose death in New York City (NYC) increased 26% from 2000 to 2015, with a notable decrease in rate from 2006 to 2010. Beginning in 2016, the synthetic opioid fentanyl entered the NYC illicit drug market and has been associated with large increases in overdose death. This study assessed NYC trends in opioid-involved overdose death prior to fentanyl to understand the contribution of specific opioids and inform overdose prevention strategies.. Data were derived from death certificates linked to postmortem toxicology testing. We stratified cases into three mutually exclusive groups: (1) heroin without opioid analgesics (OAs); (2) OAs without heroin; and (3) the combination of heroin and OAs. We calculated mortality rates by year, and compared rates by the demographic characteristics age, sex, and race/ethnicity. Joinpoint regression identified junctures in trends between 2000 and 2015.. Rates of overdose death involving heroin without OAs decreased from 2006 to 2010, then increased from 2010 to 2015 among males, persons age 15 to 54, and Blacks and Whites. Rates of overdose death involving OAs with and without heroin increased from 2000 to 2015 across all demographic subgroups.. The identified trends in overdose death are suggestive of demographic shifts in drug use. In particular, the tamper-resistant reformulation of oxycodone 80 mg may have increased the use of heroin among primary OA users. Notably, older adults may have had established heroin use practices prior to the proliferation of OAs and thus may have been less likely to modify drug use practices.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Cross-Sectional Studies; Death Certificates; Drug Overdose; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Middle Aged; Mortality; New York City; Opioid-Related Disorders; Oxycodone; Young Adult

Topics: Adult; Analgesics, Opioid; Cocaine; Drug Overdose; Drug Trafficking; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Methamphetamine; Middle Aged; Ohio; Opioid-Related Disorders

Although much is known about the correlates of heroin overdose, less is known about pharmaceutical opioid (PO) overdose. This study aimed to examine correlates of opioid overdose deaths by opioid and compare correlates between opioids.. Analysis of opioid overdose deaths in Australia between 2000-2015, extracted from the National Coronial Information System (NCIS). The NCIS is an online database of deaths reportable to the coroner, and contains coroner's findings, autopsy and toxicology reports. Deaths were categorized into mutually exclusive groups: 1) Heroin deaths; and 2) PO deaths (excluding heroin). PO deaths were examined by individual opioid.. There were 10,795 opioid overdose deaths over the study period. Relative to deaths occurring in major cities, deaths in regional/remote areas had 15.2 (95 % CI: 11.5-20.2) times the risk of being attributed to pharmaceutical fentanyl than heroin. Relative to deaths among people without a recorded history of chronic pain, deaths among people with a recorded history of chronic pain had a 1.9-10.7-fold increased risk of the death being attributed to POs than heroin. Deaths among people with a recorded history of substance use problems where the opioid was injected prior to death had 7.2 and 1.7 times the risk of being attributed to methadone and pharmaceutical fentanyl (respectively) than heroin.. Findings suggest the need to: educate PO consumers about the risks of overdose at the time of prescribing; increase coverage and engagement in opioid dependence treatment (particularly in regional/remote areas); and increase uptake of take-home naloxone to reduce opioid overdose mortality.

Topics: Adolescent; Adult; Analgesics, Opioid; Australia; Chronic Pain; Drug Overdose; Drug Prescriptions; Female; Fentanyl; Heroin; Humans; Male; Methadone; Middle Aged; Morphine; Naloxone; Opioid-Related Disorders; Tramadol; Young Adult

Research on adolescent heroin use has focused on national surveillance, access, prevalence of use, and overdose deaths, however, to our knowledge, no study has examined local-level differences in the prevalence of adolescent heroin use in the context of nonmedical prescription opioid (NMPO) use. This study characterizes heroin and NMPO use among US high school students in select urban areas by sex and race/ethnicity.. Data are from 21 urban school districts that participate in CDC's Local Youth Risk Behavior Surveillance System. We describe 2017 prevalence estimates (and 95 % confidence intervals) of lifetime heroin and NMPO use among youth stratified by sex and race/ethnicity (i.e., White, Black, Hispanic/Latino).. The highest estimates of heroin use were in Baltimore, MD (7.6 %), Shelby County, TN (6.3 %), and Duval County, FL (6.1 %), whereas NMPO use was highest in Duval County, FL (18.1 %), Cleveland, OH (18.0 %), and Shelby County, TN (16.8 %). Heroin use was higher among boys than girls, especially among Hispanic/Latino boys in Duval County (12.3 %) and Black boys in Baltimore (10.9 %). NMPO use was highest among Hispanic/Latino girls (21.3 %) and White girls (19.9 %) in Duval County.. While some cities and subpopulations with high levels of adolescent heroin use also had elevated levels of NMPO use, others did not, illustrating the complexities of this opioid epidemic.

Topics: Adolescent; Baltimore; Black or African American; Ethnicity; Female; Heroin; Hispanic or Latino; Humans; Male; Opioid-Related Disorders; Population Surveillance; Prevalence; Risk-Taking; Schools; Students; Tennessee; Urban Population; White People

Opioids have high abuse potential and pose a major public health concern. Yet, a large percentage of individuals exposed to opioids do not develop problematic use. Individual differences in opioid abuse potential are not well understood.. This within-subject (N = 16), double-blind, double-dummy, human laboratory study evaluated individual differences in response to dose (placebo, low, medium, high) following administration of heroin and hydromorphone through intravenous and subcutaneous routes, in opioid-experienced but non physically-dependent participants. Outcomes were self-reported visual analog scale (VAS) ratings (High, Liking, Drug Effect, Good Effect, Rush), pupil diameter change from baseline, and crossover point on the Drug vs. Money questionnaire. The degree to which results were consistent across measures within an individual was assessed using a mixed-effects model from which an intraclass correlation coefficient measure of between and within-subject variance was derived.. The mixed effects model fit was significant (p < 0.0001) and revealed that 85.5% of the explainable variance was due to between-subject effects, suggesting the responses within an individual were highly consistent. Visual inspection reveals a myriad response pattern across participants, with some demonstrating classic dose-effect responses and others not differentiating any active doses from placebo.. Data suggest the abuse potential of opioids is significantly different between individuals but that the experience within an individual is highly consistent. Research to prospectively characterize and evaluate mechanisms underlying these differences is warranted and may provide a foundation to help identify persons at heightened risk of transitioning from opioid exposure to misuse and/or opioid use disorder.

Topics: Administration, Intravenous; Adult; Analgesics, Opioid; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Emotions; Female; Heroin; Humans; Hydromorphone; Individuality; Injections, Subcutaneous; Male; Middle Aged; Opioid-Related Disorders; Self Report

The United States is currently in the midst of the worst drug epidemic in its history, with nearly 64,000 overdose deaths in 2016. In response, pharmaceutical companies have begun introducing abuse-deterrent painkillers, pills with properties that make the drug more difficult to misuse. The first such painkiller, a reformulated version of OxyContin, was released in 2010. Previous research has found no net effect on opioid mortality, with users substituting from OxyContin toward heroin. This paper explores health effects of the reformulation beyond mortality. In particular, I show that heroin is substantially more likely to be injected than OxyContin, increasing exposure to blood-borne diseases. Exploiting variation across states in OxyContin misuse prior to the reformulation, I find relative increases in the spread of hepatitis B and C in states most likely to be affected by the reformulation. In aggregate, the estimates suggest that absent the reformulation, we would have observed approximately 76% fewer cases of hepatitis C and 53% fewer cases of hepatitis B from 2011 to 2015. I find some suggestive evidence that the reformulation also lead to increases in HIV and hepatitis A, although these findings are less robust. These findings have important implications for future policies addressing the opioid crisis.

Topics: Analgesics, Opioid; Drug Administration Routes; Drug Overdose; Hepatitis A; Hepatitis B; Hepatitis C; Heroin; HIV Infections; Humans; Opioid-Related Disorders; Oxycodone; Prescription Drug Misuse; Substance Abuse, Intravenous; Technology, Pharmaceutical; United States

Heroin production for external markets and low rates of use in Mexico have had a long history. A recent shift toward an increase in use and related problems calls for the evaluation of treatment needs in order to draw recommendations for policies.. The objectives were to identify predictors of choice of treatment and barriers to care among persons that had been with no treatment. The study included a convenience sample of 600 face-to-face interviews of people 18 years of age and older and a rapid HIV and HCV tests in three cities on Mexico's Northern Border: Ciudad Juárez, San Luis Río Colorado and Tijuana. The choice of treatment (methadone, other pubic or private treatments with no experience with methadone maintenance and only self-help or religious care), was analyzed though a multiple logistic multimodal regression analysis. Informed consents to be interviewed and for HIC and HIV were signed by interviewers.. The majority of persons interviewed were males (89.7%) with an average age of 40. Having emigrated to the United States and a greater length of heroin use predicted seeking methadone treatment versus public or private treatment or informal care. The most important barriers to care were lack of information and stigma. HIC, HIV and other infectious and chronic diseases including depression were often unattended.. There is a need to reform treatment policies in order to cover this w emerging and demanding problem.

Topics: Adolescent; Adult; Female; Heroin; Humans; Male; Methadone; Mexico; Opioid Epidemic; Opioid-Related Disorders; Opium; Self-Help Groups; United States; Young Adult

Heroin and fentanyl are the overwhelming and increasing cause of opioid deaths in Milwaukee County, Wisconsin. We reviewed all drug and opioid deaths from 2013 to 2017 to delineate the specific opioid drugs involved and changes in their incidence. From 2013 to 2017, 980 deaths were due to opioids, rising from 184 in 2013 to 337 in 2017. In 2017, opioid deaths exceeded combined non-natural deaths from homicide and suicide. Illicit heroin and fentanyl/analogs caused 84% of opioid deaths and 80% of drug deaths, with no increase in deaths due to oral prescription drugs such as oxycodone and hydrocodone. Any approach to decreasing this dramatic increase in opioid deaths should first focus on interdicting the supply and cheap availability of these illicit opioids. Fentanyl and its analogs represent the most deadly opioids and the greatest threat to human life in our population.

Topics: Analgesics, Opioid; Buprenorphine; Coroners and Medical Examiners; Fentanyl; Heroin; Humans; Hydrocodone; Illicit Drugs; Incidence; Methadone; Opioid-Related Disorders; Oxycodone; Substance-Related Disorders; Wisconsin

Acetyl fentanyl (N-[1-phenethylpiperidin-4-yl]-N-phenylacetamide) is a potent opioid analgesic with no medicinal uses. We report deaths between 2016 and 2017 at the Medical Examiner's Office in Detroit, MI where acetyl fentanyl was found in the decedent's blood and compare them to previously published deaths between 2015 and 2016. The recent cases (cohort B) had a mean acetyl fentanyl concentration of 0.9 ng/mL (range: 0.1-5.3 ng/mL) and an associated higher concentration of fentanyl along with multiple other drugs present. The older cases (cohort A) had higher concentrations of acetyl fentanyl (mean: 8.9 ng/mL; range: 0.28-37 ng/mL) with lower, yet still toxic, concentrations of fentanyl. We conclude that the cause of death in these recent cases was likely multiple drug toxicity with fentanyl and that the consistently observed lower peripheral blood concentrations of acetyl fentanyl are most likely an artifact in the manufacture of the consumed illicit fentanyl.

Topics: Adult; Analgesics, Opioid; Benzodiazepines; Central Nervous System Depressants; Chromatography, Liquid; Cocaine; Cohort Studies; Coroners and Medical Examiners; Drug Overdose; Ethanol; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Mass Spectrometry; Michigan; Opioid-Related Disorders; Racial Groups; Urban Population

Opioid agonist treatment (OAT) is currently the most effective treatment for people with opioid dependence. In most countries, however, access to the whole range of effective medications is restricted. This study aims to model the distribution of different OAT medications within a naturalistic and relatively unrestricted treatment setting (Zurich, Switzerland) over time, and to identify patient characteristics associated with each medication.. We used generalized estimating equation analysis with data from the OAT register of Zurich and the Swiss register for heroin-assisted treatment (HAT) to model and forecast the annual proportion of opioids applying exponential distributions until 2018 and patient characteristics between 1992 and 2015.. Data from 11 895 patients were included in the analysis. Methadone remains the mainstay of OAT, being prescribed to two-thirds of patients. Following its approval, the proportion of HAT increased rapidly and is now constant at 12.16% [95% confidence interval (CI) = 11.15-13.17]. The initial increase of proportions of buprenorphine or slow-release oral morphine (SROM) following their approval for OAT was slower. While in 2014 both medications had a proportion of 10.2% and 10.3%, respectively, our model predicts a further increase of SROM to 19.9% in 2018, with a ceiling level of 25.19% (21.40-28.98%) thereafter. SROM patients display characteristics similar to those treated with methadone; buprenorphine patients show the highest social integration; and HAT patients are the most homogeneous group, with highest mean age, most widespread injecting experience and lowest social integration.. Based on data from Zurich, Switzerland from 1992 to 2015, there is no evidence for an excessive demand for a single medication in a naturalistic and liberal opioid agonist treatment setting. Rather, the specific patient characteristics associated with each medication underline the need for diversified treatment options for opioid dependence.

Topics: Adult; Age Factors; Analgesics, Opioid; Buprenorphine; Employment; Family Relations; Female; Friends; Heroin; Housing; Humans; Male; Methadone; Middle Aged; Morphine; Opiate Substitution Treatment; Opioid-Related Disorders; Social Integration; Social Participation; Substance Abuse, Intravenous; Switzerland

In 2016, the number of overdose deaths involving illicitly-manufactured fentanyl (IMF) surpassed heroin and prescription opioid deaths in the United States for the first time, with IMF-involved overdose deaths increasing more than 500% across 10 states from 2013 to 2016. IMF is an extremely potent synthetic opioid that is regularly mixed with heroin and often sold to unwitting consumers. Community-based organizations have started to distribute fentanyl test strips (FTS) as a strategy to identify IMF in street purchased products. We investigated the association between FTS use and changes in drug use behavior and perceived overdose safety among a community-based sample of people who inject drugs (PWID) in the United States.. Between September-October 2017, a total of 125 PWID completed an online survey about their most recent FTS use in Greensboro, North Carolina. Our first outcome of interest included whether PWID engaged in any of the following changes in drug use behavior after using FTS: used less than usual, administered tester shot, pushed syringe plunger slower than usual, and snorted instead of injected. Our second outcome of interest was whether PWID felt that FTS use made them feel better able to protect themselves from overdose. We conducted bivariate and multivariate analyses to determine the association between FTS use and these two outcomes.. Overall, 63% of the sample reported a positive FTS test result and 81% reported using FTS prior to consuming their drugs. For the outcomes, 43% reported a change in drug use behavior and 77% indicated increased perceived overdose safety by using FTS. In multivariable models adjusting for demographic and FTS correlates, PWID with a positive FTS test result had five times the odds of reporting changes in drug use behavior compared to those with a negative result. PWID who used the FTS after drug consumption were 70% less likely to report behavioral changes at subsequent drug consumption compared to those who used it before consumption. PWID who were not existing clients of the syringe services program had four times higher odds than existing clients to report increased overdose safety from using FTS.. We found that using FTS and receiving a positive test result was associated with changes in drug use behavior and perceptions of overdose safety. FTS may represent an effective addition to current overdose prevention efforts when included with other evidence-based strategies to prevent opioid overdose and related harm.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Middle Aged; Needle-Exchange Programs; North Carolina; Opioid-Related Disorders; Surveys and Questionnaires; United States

Opioid overprescribing is a major driver of the current opioid overdose epidemic. However, annual opioid prescribing in the USA dropped from 782 to 640 morphine milligram equivalents per capita between 2010 and 2015, while opioid overdose deaths increased by 63%. To better understand the role of prescription opioids and health care utilization prior to opioid-related overdose, we analyzed the death records of decedents who died of an opioid overdose in Illinois in 2016 and linked to any existing controlled substance monitoring program (CSMP) and emergency department (ED) or hospital discharge records. We found that of the 1893 opioid-related overdoses, 573 (30.2%) decedents had not filled an opioid analgesic prescription within the 6 years prior to death. Decedents without an opioid prescription were more likely to be black (33.3% vs 20.2%, p < .001), Hispanic (16.3% vs 8.8%, p < .001), and Chicago residents (46.8% vs 25.6%, p < .001) than decedents with at least one filled opioid prescription. Decedents who did not fill an opioid prescription were less likely to die of an overdose involving prescribed opioids (7.3% vs 19.5%, p < .001) and more likely to fatally overdose on heroin (63% vs 50.4%, p < .001) or fentanyl/fentanyl analogues (50.3% vs 41.8%, p = .001). Between 2012 and the time of death, decedents without an opioid prescription had fewer emergency department admissions (2.5 ± 4.2 vs 10.6 ± 15.8, p < .001), were less likely to receive an opioid use disorder diagnosis (41.3% vs 47.5%, p = .052), and were less likely to be prescribed buprenorphine for opioid use disorder treatment (3.3% vs 8.6%, p < .001). Public health interventions have often focused on opioid prescribing and the use of CSMPs as the core preventive measures to address the opioid crisis. We identified a subset of individuals in Illinois who may not be impacted by such interventions. Additional research is needed to understand what strategies may be successful among high-risk populations that have limited opioid analgesic prescription history and low health care utilization.

Topics: Adult; Analgesics, Opioid; Black or African American; Buprenorphine; Chicago; Drug Overdose; Female; Fentanyl; Heroin; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acceptance of Health Care; Practice Patterns, Physicians'; Public Health; Risk Factors

The exponential increase in chronic opioid consumers resulted in more challenges regarding post-operative pain management. Considering the usual hyperalgesic response to pain and the increased opioid-tolerance, a multidrug approach should be desirable.. We described the strategy in pain management of a patient receiving methadone maintenance treatment, who underwent surgery associated with moderate post-operative pain. The combination of balanced general anaesthesia and intraoperative continuous low-dose infusion of ketamine assured an appropriate control of post-operative pain without increasing opioid consumption. Besides, it was not associated with psychomimetic effects.. Ketamine can effectively reduce opioid requirements in chronic opioid users on methadone maintenance therapy and should therefore be considered promptly as part of a multimodal perioperative analgesia management in this category of patients.

Topics: Analgesics, Opioid; Heroin; Humans; Hyperalgesia; Ketamine; Male; Methadone; Middle Aged; Opioid-Related Disorders; Pain Management; Pain, Postoperative; Perioperative Care; Postoperative Period

Opioid drug use is a major cause of premature mortality, with opioid substitution therapy the leading intervention. As methadone-clients age, non-drug-related deaths (non-DRDs) predominate and DRD-risks increase differentially, quadrupling at 45+ years for methadone-specific DRDs.. 36,606 methadone-prescription-clients in Scotland during 2009-2015 were linked to mortality records to end-2015 by their Community Health Index (CHI). Cohort-entry, also baseline quantity of prescribed methadone, were defined by clients' first CHI-identified methadone-prescription during 2009-2015. National Records of Scotland identified non-DRDs from DRDs; and provided ICD10 codes for underlying and co-present causes of death. Methadone-specific DRD means methadone was implicated in DRD but neither heroin nor buprenorphine.. During 193,800 person-years of follow-up, 1939 non-DRDs (59%) and 1323 DRDs occurred, of which 546 were methadone-specific. Predominant underlying ICD10 chapters for non-DRDs were: neoplasm (377); external causes (341); diseases of digestive (303), circulatory (286) or respiratory (212) system. As methadone-clients aged, the non-DRD proportion of their deaths increased from 54% (717/1318) at 35-44 years to 89% (372/417) at 55+ years. After allowing for DRDs' opioid-specificity, age-group and quintile for last-prescribed methadone, there was a significant, positive interaction for co-present circulatory disease between top-quintile for prescribed methadone and 45+ years at death (p = 0.033 after Bonferroni); not for digestive or respiratory co-presence.. Circulatory disease is the co-morbidity most likely implicated in the quadrupling of methadone-specific DRD-risk at 45+ years; followed by digestive disease. Cultural shift is needed in treatment-services because degenerative non-DRDs predominate as methadone-clients age. Future linkage-studies should access hospitalizations and methadone-daily-dose.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cause of Death; Cohort Studies; Female; Heroin; Humans; Male; Mental Status and Dementia Tests; Methadone; Middle Aged; Neurocognitive Disorders; Opiate Substitution Treatment; Opioid-Related Disorders; Scotland; Young Adult

Almost a third of opioid overdose deaths also involve benzodiazepines, but few representative studies have examined misuse of benzodiazepines and other tranquilizers by adults who misuse opioids. This study estimated the prevalence and frequency of tranquilizer misuse among adults who misuse opioids and examined characteristics associated with tranquilizer misuse.. A sample of adults who misused opioids in the past year (n = 36,043) were identified in the National Surveys on Drug Use and Health 2002-2014. Tranquilizer misuse prevalence was estimated for each year from 2002 to 2014. Data were then pooled for all years. Multiple logistic and Poisson regression was used to identify characteristics independently associated with the prevalence and frequency tranquilizer misuse respectively.. Twenty-eight percent of adults who misused illicit opioids in the past year also reported tranquilizer misuse. This prevalence did not change notably over the 13-year period examined. Among those who misused opioids, meeting criteria for opioid abuse or dependence was associated with a 134% increase in the odds of misusing tranquilizers during the same year. Other characteristics associated with increased odds of tranquilizer misuse included being aged 18-25 years, non-Hispanic white, uninsured, unemployed, and having used heroin.. Tranquilizer misuse is common among adults who misuse opioids and has not changed substantially over the past decade. Meeting criteria for abuse or dependence of opioids is associated with more than double the odds of tranquilizer misuse among adults who misuse opioids.

Topics: Adolescent; Adult; Benzodiazepines; Drug Overdose; Female; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Prevalence; Tranquilizing Agents; United States; Young Adult

In the 1990s, a trial of prescribing pharmaceutical heroin for people with opioid-dependence had support from Australian State Health Ministers. However, in 1997 the proposal was vetoed by the federal Prime Minister in face of a negative tabloid media campaign. The debate then shifted to abstinence-orientated treatments. Later on, reduced heroin availability took opioid-related harms away from public sight. In this commentary, we aimed to explore the current need and the options to implement such program, lately referred to as supervised injectable opioid treatment (SIOT), in Australia. We argue that with the aging populations of opioid-dependent people who have not benefited from existing treatment options, increased misuse of prescription opioids, rising overdose rates, and the risk of unfolding overdose crisis, it seems timely to pilot SIOT here. Since the 1990s, seven RCTs as summarised in two systematic literature reviews, demonstrated that SIOT is effective for treatment-resistant opioid dependence. A sustainable SIOT model should, however, respond to key concerns related to its delivery, such as the lack of a patient exit strategy and the high cost of indefinite treatment. Evidence from long-term studies seem to support the notion that SIOT could be provided as a medium duration treatment (as opposed to short-term or indefinite), with the clear aim to stabilise patients, gradually wean them off injectable medication and transfer to opioid assisted treatment (OAT). Also, SIOT could be integrated into the existing public OAT clinics in Australia. This would reduce costs, but also provide a more patient-centred response to opioid dependence and further improve the acceptability and efficiency of OAT. The controversy that developed in the past should be mitigated by advances in research since the first Australian enquiry, use of a registered medication (open-label hydromorphone) rather than pharmaceutical heroin, and setting up clear treatment aims.

Topics: Analgesics, Opioid; Australia; Drug Overdose; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Randomized Controlled Trials as Topic; Substance Abuse, Intravenous

This study focused on formulating conjugate vaccines targeting oxycodone and heroin for technology transfer, good manufacturing practice (GMP), and clinical evaluation. Lead vaccines used the highly immunogenic carrier protein keyhole limpet hemocyanin (KLH), which poses formulation problems because of its size. To address this barrier to translation, an oxycodone-based hapten conjugated to GMP-grade subunit KLH (OXY-sKLH) and adsorbed on alum adjuvant was studied with regard to carbodiimide coupling reaction time, buffer composition, purification methods for conjugates, conjugate size, state of aggregation, and protein/alum ratio. Vaccine formulations were screened for post-immunization antibody levels and efficacy in reducing oxycodone distribution to the brain in rats. While larger conjugates were more immunogenic, their size prevented characterization of the haptenation ratio by standard analytical methods and sterilization by filtration. To address this issue, conjugation chemistry and vaccine formulation were optimized for maximal efficacy, and conjugate size was measured by dynamic light scattering prior to adsorption to alum. An analogous heroin vaccine (M-sKLH) was also optimized for conjugation chemistry, formulated in alum, and characterized for potency against heroin in rats. Finally, this study found that the efficacy of OXY-sKLH was preserved when co-administered with M-sKLH, supporting the proof of concept for a bivalent vaccine formulation targeting both heroin and oxycodone. This study suggests methods for addressing the unique formulation and characterization challenges posed by conjugating small molecules to sKLH while preserving vaccine efficacy.

Topics: Animals; Hemocyanins; Heroin; Humans; Opioid-Related Disorders; Oxycodone; Rats; Vaccines; Vaccines, Conjugate

The study aims to develop and validate algorithms to identify and classify opioid overdoses using claims and other coded data, and clinical text extracted from electronic health records using natural language processing (NLP).. Primary data were derived from Kaiser Permanente Northwest (2008-2014), an integrated health care system (~n > 475 000 unique individuals per year). Data included International Classification of Diseases, Ninth Revision (ICD-9) codes for nonfatal diagnoses, International Classification of Diseases, Tenth Revision (ICD-10) codes for fatal events, clinical notes, and prescription medication records. We assessed sensitivity, specificity, positive predictive value, and negative predictive value for algorithms relative to medical chart review and conducted assessments of algorithm portability in Kaiser Permanente Washington, Tennessee State Medicaid, and Optum.. Code-based algorithm performance was excellent for opioid-related overdoses (sensitivity = 97.2%, specificity = 84.6%) and classification of heroin-involved overdoses (sensitivity = 91.8%, specificity = 99.0%). Performance was acceptable for code-based suicide/suicide attempt classifications (sensitivity = 70.7%, specificity = 90.5%); sensitivity improved with NLP (sensitivity = 78.7%, specificity = 91.0%). Performance was acceptable for the code-based substance abuse-involved classification (sensitivity = 75.3%, specificity = 79.5%); sensitivity improved with the NLP-enhanced algorithm (sensitivity = 80.5%, specificity = 76.3%). The opioid-related overdose algorithm performed well across portability assessment sites, with sensitivity greater than 96% and specificity greater than 84%. Cross-site sensitivity for heroin-involved overdose was greater than 87%, specificity greater than or equal to 99%.. Code-based algorithms developed to detect opioid-related overdoses and classify them according to heroin involvement perform well. Algorithms for classifying suicides/attempts and abuse-related opioid overdoses perform adequately for use for research, particularly given the complexity of classifying such overdoses. The NLP-enhanced algorithms for suicides/suicide attempts and abuse-related overdoses perform significantly better than code-based algorithms and are appropriate for use in settings that have data and capacity to use NLP.

Topics: Algorithms; Analgesics, Opioid; Drug Overdose; Electronic Health Records; Female; Heroin; Humans; Male; Middle Aged; Natural Language Processing; Opioid-Related Disorders; Sensitivity and Specificity; Suicide; Suicide, Attempted

Among all the treatment methods developed so far, opioid agonist treatment (OAT) is the most effective therapy for opioid dependence. While methadone (MTD) is the most commonly used, fewer data are available on alternative opioid agonist. The aim of this study was to assess the efficacy of buprenorphine (BUP) and slow-released morphine compared to MTD with regard to the reduction of concomitant heroin and cocaine use.. This cross-sectional study included 105 patients receiving MTD, BUP, or slow-release morphine as opioid agonist therapy at the Psychiatric Hospital of Zurich. Illicit drug use was assessed using a retrospective 3-month hair toxicology analysis to quantify concentrations of heroin degradation products and metabolites, as well as cocaine and cocaine metabolites. We have also collected self-reports, but in the data of the study, only the results of the hair analysis were considered.. BUP-treated patients showed lower rates of illicit opiate consumption in comparison to the group treated with MTD or slow-released morphine (p < 0.05). The proportion of heroin-positive hair samples associated with slow-release morphine treatment was similar to the proportion associated with MTD treatment. Neither the MTD vs. slow-released morphine groups nor the BUP vs. MTD groups showed significant differences in the number of patients consuming cocaine although patients in the BUP group had significantly lower concentrations of cocaine in hair testing compared to the patients in the MTD group. Prevalence of cocaine consumption was also significantly lower in the BUP group compared to patients in the slow-release morphine group (p < 0.05).. This study suggests that BUP OAT is associated with reduced additional opiate co-use.

Topics: Adult; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Cocaine; Cross-Sectional Studies; Delayed-Action Preparations; Female; Heroin; Humans; Male; Methadone; Morphine; Opiate Substitution Treatment; Opioid-Related Disorders; Switzerland

On May 31, 2017, Ohio Attorney General Mike DeWine took a step in fighting Ohio's opioid epidemic, bringing the first of many lawsuits against five top pharmaceutical companies. However, under Federal and State law, there is an exception called the Learned Intermediary Doctrine, which can absolve drug manufacturers of liability from any misconduct that might be found and transfer that liability to a treating physician. This exception is the way many drug manufacturers were able to avoid being held responsible in the past. This Note proposes that with the current pending lawsuit in the State of Ohio, an exception to the Learned Intermediary Doctrine should be introduced. This Note begins with a discussion of opioids and how these drugs have become such an aggressive problem in a very short amount of time in Ohio. Part II talks about the role the government can play and the drug manufacturers have played and continue to play in the availability of opioids. It discusses the effect these pharmaceutical companies have had on this problem and in increasing this problem. Part II also discusses why this is a problem and why this problem matters. Further, it talks about the steps that have already been taken by the Ohio Legislature to combat the opioid problems. Finally, it delves into a discussion of what this current lawsuit means for fighting and decreasing the opioid problem and how it will directly affect the heroin epidemic in Ohio.

Topics: Drug Industry; Heroin; Humans; Legislation as Topic; Liability, Legal; Ohio; Opioid Epidemic; Opioid-Related Disorders; Physicians; Policy Making; United States; United States Food and Drug Administration

To inform overdose prevention, this study assessed both recent trends in opioid overdose mortality across opioid categories and receipt of prescription opioid analgesics among Veterans who died from overdose in the Veterans Health Administration.. Using Veterans Health Administration records linked to National Death Index data, annual cohorts (2010-2016) of Veterans who received Veterans Health Administration care were obtained and were examined by opioid overdose categories (natural/semisynthetic opioids, heroin, methadone, and other synthetic opioids) on (1) overdose rates and changes in rates adjusted for age, sex, and race/ethnicity; and (2) Veterans Health Administration prescription opioid receipt. Analyses were conducted in 2018.. The overall rate of opioid overdose among Veterans increased from 14.47 per 100,000 person-years in 2010 to 21.08 per 100,000 person-years in 2016 (adjusted rate ratio=1.65, 95% CI=1.51, 1.81). There was a decline in methadone overdose (adjusted rate ratio=0.66, 95% CI=0.51, 0.84) and no significant change in natural/semisynthetic opioid overdose (adjusted rate ratio=1.08, 95% CI=0.94, 1.24). However, the synthetic opioid overdose rate (adjusted rate ratio=5.46, 95% CI=4.41, 6.75) and heroin overdose rate (adjusted rate ratio=4.91, 95% CI=3.92, 6.15) increased substantially. Among all opioid overdose decedents, prescription opioid receipt within 3 months before death declined from 54% in 2010 to 26% in 2016.. Opioid overdose rates among Veterans Health Administration Veterans increased because of increases in heroin and synthetic opioid overdose rates. Prescriptions of opioids declined among patients who died from all categories of opioid overdose; by 2016, only a minority received an opioid analgesic from Veterans Health Administration within 3 months of overdose. Future prevention efforts should extend beyond patients actively receiving opioid prescriptions.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Heroin; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Prescription Drug Misuse; United States; United States Department of Veterans Affairs; Veterans

To enhance automated methods for accurately identifying opioid-related overdoses and classifying types of overdose using electronic health record (EHR) databases.. We developed a natural language processing (NLP) software application to code clinical text documentation of overdose, including identification of intention for self-harm, substances involved, substance abuse, and error in medication usage. Using datasets balanced with cases of suspected overdose and records of individuals at elevated risk for overdose, we developed and validated the application using Kaiser Permanente Northwest data, then tested portability of the application using Kaiser Permanente Washington data. Datasets were chart-reviewed to provide a gold standard for comparison and evaluation of the automated method.. The method performed well in identifying overdose (sensitivity = 0.80, specificity = 0.93), intentional overdose (sensitivity = 0.81, specificity = 0.98), and involvement of opioids (excluding heroin, sensitivity = 0.72, specificity = 0.96) and heroin (sensitivity = 0.84, specificity = 1.0). The method performed poorly at identifying adverse drug reactions and overdose due to patient error and fairly at identifying substance abuse in opioid-related unintentional overdose (sensitivity = 0.67, specificity = 0.96). Evaluation using validation datasets yielded significant reductions, in specificity and negative predictive values only, for many classifications mentioned above. However, these measures remained above 0.80, thus, performance observed during development was largely maintained during validation. Similar results were obtained when evaluating portability, although there was a significant reduction in sensitivity for unintentional overdose that was attributed to missing text clinical notes in the database.. Methods that process text clinical notes show promise for improving accuracy and fidelity at identifying and classifying overdoses according to type using EHR data.

Topics: Analgesics, Opioid; Datasets as Topic; Drug Overdose; Electronic Health Records; Heroin; Humans; Natural Language Processing; Opioid-Related Disorders; Predictive Value of Tests; Risk; Self-Injurious Behavior; Sensitivity and Specificity; Washington

Topics: Adult; Aged; Analgesics, Opioid; Cross-Sectional Studies; Female; Heroin; Humans; Loneliness; Male; Methadone; Middle Aged; New England; Northwestern United States; Opiate Substitution Treatment; Opioid-Related Disorders; Sex Factors; Treatment Outcome; Young Adult

Topics: Analgesics, Opioid; Communicable Diseases; Drug Users; Fentanyl; Hepatitis; Heroin; HIV Infections; Humans; Opioid-Related Disorders; Staphylococcal Infections; Staphylococcus aureus; United States

Recent data suggest an increase in use of heroin and non-medical use of prescription opioids (POs) in the United States, but it is unclear if these trends are consistent across racial/ethnic groups. In a nationwide prevalence study, 69,140 patients newly admitted to an opioid treatment program (OTP) completed a brief self-administered survey of past month heroin use and PO misuse from January 2005 through September 2016. We calculated heroin use and PO misuse prevalence rates, and prevalence rate ratios of Black and Latino OTP entrants compared to White entrants over time. Initially, Black and Latino respondents reported much higher prevalence of heroin use and much lower prevalence of PO misuse than White respondents. Heroin use increased among White respondents, while it decreased among Black respondents, resulting in rates that were no longer significantly different. PO misuse prevalence decreased among White respondents while it increased among Black respondents, but remained significantly higher among White respondents. Heroin use decreased and PO misuse increased among Latino respondents during the late 2000s, but these trends largely reversed in more recent years. Among OTP entrants, racially/ethnically disparate rates of heroin use, and to a lesser extent, of PO misuse have become more similar over time. These trends were stronger when analysis was restricted to OTP entrants who either had no previous OTP history or were younger. To understand potential impacts of interventions to deter PO misuse and to maximize the effectiveness of OTPs it is important to consider potential changes in opioid use across racial/ethnic groups.

Topics: Adult; Analgesics, Opioid; Black or African American; Female; Heroin; Hispanic or Latino; Humans; Male; Opioid-Related Disorders; Prescription Drug Misuse; Prevalence; United States; White People; Young Adult

Topics: Adult; Analgesics, Opioid; Antisocial Personality Disorder; Clinical Trials as Topic; Combined Modality Therapy; Deep Brain Stimulation; Drug Overdose; Heroin; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Social Class

To assess cohort effects in prescription opioid and heroin overdose mortality in the United States.. Using the National Center for Health Statistics' multiple-cause-of-death file for 1999 to 2014, we performed an age-period-cohort analysis of drug overdose mortality in the United States.. Compared with those born in 1977 and 1978, individuals born between 1947 and 1964 experienced excess risks of prescription opioid overdose death (e.g., for the 1955-1956 birth cohort, rate ratio [RR] = 1.27; 95% confidence interval [CI] = 1.09, 1.48) and of heroin overdose death (e.g., for the 1953-1954 birth cohort, RR = 1.32; 95% CI = 1.11, 1.57). Those born between 1979 and 1992 also experienced an increased risk of heroin overdose death (e.g., for the 1989-1990 birth cohort, RR = 1.23; 95% CI = 1.01, 1.50). The cohort effects were consistent between sexes.. Individuals born between 1947 and 1964 and between 1979 and 1992 are particularly afflicted by the opioid epidemic. Intervention programs are needed to reduce the excess overdose mortality in these specific demographic groups.

Topics: Adolescent; Adult; Age Distribution; Aged; Analgesics, Opioid; Cohort Studies; Drug Overdose; Female; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Socioeconomic Factors; United States; Young Adult

Naloxone is a safe and effective antidote for reversing opioid overdose. Layperson administration of naloxone is increasingly common, yet little is known about demographic and clinical factors associated with opioid users' likelihood of having administered naloxone to another opioid user who had overdosed. We examined predictors of reported naloxone administration in the past year.. Four hundred and sixty-eight patients were interviewed upon admission to brief, inpatient opioid detoxification between May and December of 2015. Between group differences were tested using t-tests for differences in means and χ. Participants averaged 32years of age, 28.9% were female, and 86.8% were White. Most (86.8%) reported detoxifying from heroin, 69.0% had injected drugs in the last 30days. One sixth (n=68) of those detoxifying from heroin, but none of those detoxifying from other opioids (n=62) had administered naloxone in the past year. Among the small number of Black/African American participants (n=20), none had administered naloxone, although 90% were heroin users. Respondents were more likely to have administered naloxone if they reported recent injection drug use (IDU), had a history of overdose, or witnessed an overdose in the past year (ps<0.05), even though less than one-third of bystanders of overdose reported administering naloxone.. Higher opioid-related mortality risk (heroin use, IDU, past overdose) was associated with greater likelihood of reported naloxone administration in the past year. The non-use of naloxone among certain groups-prescription pill users and Blacks-was unexpected.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Drug Users; Female; Heroin; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation of 1 was described in the route in the synthesis of 2 (DiAmHap). A scalable procedure was developed to install the C-3 amido group. Using the Boc protectng group in 18 allowed preparation of 1 in an overall yield of 53% from 4 and eliminated the necessity of preparing the diamide 13. Hapten 1 was conjugated to tetanus toxoid and mixed with liposomes containing monophosphoryl lipid A as an adjuvant. The 1 vaccine induced high anti-1 IgG levels that reduced heroin-induced antinociception and locomotive behavioral changes following repeated subcutaneous and intravenous heroin challenges in mice and rats. Vaccinated mice had reduced heroin-induced hyperlocomotion following a 50 mg/kg heroin challenge. The 1 vaccine-induced antibodies bound to heroin and other abused opioids, including hydrocodone, oxycodone, hydromorphone, oxymorphone, and codeine.

Topics: Animals; Antibodies; Cross Reactions; Female; Haptens; Heroin; Humans; Mice; Opioid-Related Disorders; Vaccines

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

In some forensic autopsies blood is not available, and other matrices are sampled for toxicological analysis. The aims of the present study were to examine whether heroin metabolites can be detected in different post-mortem matrices, and investigate whether analyses in other matrices can give useful information about concentrations in peripheral blood. Effects of ethanol on the metabolism and distribution of heroin metabolites were also investigated. We included 45 forensic autopsies where morphine was detected in peripheral blood, concomitantly with 6-acetylmorphine (6-AM) detected in any matrix. Samples were collected from peripheral blood, cardiac blood, pericardial fluid, psoas muscle, lateral vastus muscle, vitreous humor and urine. Opioid analysis included 6-AM, morphine, codeine, and morphine glucuronides. The 6-AM was most often detected in urine (n = 39) and vitreous humor (n = 38). The median morphine concentration ratio relative to peripheral blood was 1.3 (range 0-3.6) for cardiac blood, 1.4 (range 0.07-5.3) for pericardial fluid, 1.2 (range 0-19.2) for psoas muscle, 1.1 (range 0-1.7) for lateral vastus muscle and 0.4 (range 0.2-3.2) for vitreous humor. The number of 6-AM positive cases was significantly higher (P = 0.03) in the ethanol positive group (n = 6; 86%) compared to the ethanol negative group (n = 14; 37%) in peripheral blood. The distribution of heroin metabolites to the different matrices was not significantly different between the ethanol positive and the ethanol negative group. This study shows that toxicological analyses of several matrices could be useful in heroin-related deaths. Urine and vitreous humor are superior for detection of 6-AM, while concentrations of morphine could be assessed from peripheral or cardiac blood, pericardial fluid, psoas muscle and lateral vastus muscle.

Topics: Alcohol Drinking; Cadaver; Codeine; Forensic Toxicology; Glucuronides; Heroin; Humans; Morphine; Morphine Derivatives; Narcotics; Norway; Opioid-Related Disorders; Pericardial Fluid; Psoas Muscles; Quadriceps Muscle; Substance Abuse Detection; Tissue Distribution; Toxicokinetics; Vitreous Body

A growing body of evidence supports the effectiveness of injectable diacetylmorphine (i.e., heroin) for individuals with treatment-refractory opioid use disorder. Despite this evidence, and the increasing toll of opioid-associated morbidity and mortality, it remains controversial in some settings. To investigate the possible contribution of heroin-assisted treatment (HAT) to HIV treatment-related outcomes, we sought to estimate the proportion and characteristics of HIV-positive people who inject opioids that might be eligible for HAT in Vancouver, Canada.. We used data from a prospective cohort of people living with HIV who use illicit drugs in Vancouver, Canada. Using generalized estimating equations (GEE), we assessed the longitudinal relationships between eligibility for HAT, using criteria from previous clinical trials and guidelines, with behavioural, social, and clinical characteristics.. Between 2005 and 2014, 478 participants were included in these analyses, contributing 1927 person-years of observation. Of those, 94 (19.7%) met eligibility for HAT at least once during the study period. In a multivariable GEE model, after adjusting for clinical characteristics, being eligible for HAT was positively associated with homelessness, female gender, high-intensity illicit drug use, drug dealing and higher CD4 count.. In our study of HIV-positive people with a history of injection drug use, approximately 20% of participants were eligible for HAT at ≥ 1 follow-up period. Eligibility was linked to risk factors for sub-optimal HIV/AIDS treatment outcomes, such as homelessness and involvement in the local illicit drug trade, suggesting that scaling-up access to HAT might contribute to achieving optimal HIV treatment in this setting.

Topics: Adult; Analgesics, Opioid; Canada; Female; Heroin; HIV Infections; Humans; Illicit Drugs; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies

Due to the alarming rise in opioid-related overdose deaths, a public health emergency was declared in British Columbia (BC). In this study, we examined the relationship between illicit fentanyl and heroin found in seized drugs and illicit overdose deaths in BC.. An observational cross-sectional survey was conducted using BC data from Health Canada's Drug Analysis Service, which analyzes drug samples seized by law enforcement agencies, and non-intentional illicit overdoses from the BC Coroner's Service, from 2000 to 2016. Initial scatter plots and subsequent multivariate regression analysis were performed to describe the potential relationship between seized illicit fentanyl samples and overdose deaths and to determine if this differed from seized heroin and overdose deaths. Fentanyl samples were analyzed for other drug content.. Fentanyl is increasingly being found combined with other opioid and non-opioid illicit drugs. Strong positive relationships were found between the number of seized fentanyl samples and total overdose deaths (R2 = 0.97) as well as between seized fentanyl and fentanyl-detected overdose deaths (R2 = 0.99). A positive association was found between the number of seized heroin samples and total overdose deaths (R2 = 0.78).. This research contributes to the expanding body of evidence implicating illicit fentanyl use (often combined with heroin or other substances) in overdose deaths in BC. Policy makers and healthcare providers are urged to implement drug treatment and harm reduction strategies for people at risk of overdose associated with current trends in illicit opioid use.

Topics: Analgesics, Opioid; British Columbia; Cross-Sectional Studies; Drug Overdose; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Opioid-Related Disorders; Public Health

Heroin and oxycodone abuse occurs over a wide range of drug doses and by various routes of administration characterized by differing rates of drug absorption. The current study addressed the efficacy of a heroin vaccine [morphine hapten conjugated to keyhole limpet hemocyanin (M-KLH)] or oxycodone vaccine [oxycodone hapten conjugated to keyhole limpet hemocyanin (OXY-KLH)] for reducing drug distribution to brain after intravenous heroin or oxycodone, or subcutaneous oxycodone. Rats immunized with M-KLH or keyhole limpet hemocyanin (KLH) control received an intravenous bolus dose of 0.26 or 2.6 mg/kg heroin. Vaccination with M-KLH increased retention of heroin and its active metabolites 6-acetylmorphine (6-AM) and morphine in plasma compared with KLH controls, and reduced total opioid (heroin + 6-AM + morphine) distribution to brain but only at the lower heroin dose. Immunization also protected against respiratory depression at the lower heroin dose. Rats immunized with OXY-KLH or KLH control received 0.22 or 2.2 mg/kg oxycodone intravenously, the molar equivalent of the heroin doses. Immunization with OXY-KLH significantly reduced oxycodone distribution to brain after either oxycodone dose, although the magnitude of effect of immunization at the higher oxycodone dose was small (12%). By contrast, vaccination with OXY-KLH was more effective when oxycodone was administered subcutaneously rather than intravenously, reducing oxycodone distribution to brain by 44% after an oxycodone dose of 2.3 mg/kg. Vaccination also reduced oxycodone-induced antinociception. These data suggest that the efficacy of OXY-KLH and M-KLH opioid vaccines is highly dependent upon opioid dose and route of administration.

Topics: Animals; Brain; Dose-Response Relationship, Drug; Drug Administration Routes; Heroin; Male; Opioid-Related Disorders; Oxycodone; Rats; Vaccines

The sharp increase in overdose deaths involving illicit opioid use has been declared a national crisis in the United States. This growing number of overdose deaths can in part be attributed to the increased frequency of fentanyl contamination in the United States heroin supply. To combat this growing trend, we designed a vaccine containing a mixture of heroin and fentanyl hapten-conjugates as a proof-of-concept immunotherapy targeting a combination of these drugs. Rodents immunized with the admixture vaccine showed drug retention in serum and reduced distribution in the brain after administration of an intravenous bolus of heroin coadministered with fentanyl (10% w/w). Moreover, the admixture vaccine performed as well as or better than individual immunoconjugate vaccines in antinociception behavioral models and recognized six other fentanyl analogues with nanomolar affinity. Taken together, these data highlight the potential of an admixture vaccine against heroin contaminated with fentanyl.

Topics: Analgesics, Opioid; Animals; Drug Overdose; Female; Fentanyl; Heroin; Mice, Inbred BALB C; Opioid-Related Disorders; Vaccines

The United States has the ignominious distinction of leading the world in opioid prescribing,

Topics: Analgesics, Opioid; Drug and Narcotic Control; Drug Overdose; Fentanyl; Guideline Adherence; Health Personnel; Heroin; Humans; Narcotics; Opioid-Related Disorders; Politics; Practice Guidelines as Topic; Practice Patterns, Physicians'; United States

The first evidence that the hazard ratio (HR) for methadone-specific death rises more steeply with age-group than for all drug-related deaths (DRDs) came from Scotland's cohort of 33,000 methadone-prescription clients. We aim to examine, for England, whether illicit opioid users' risk of methadone-specific death increases with age; and to pool age-related HRs for methadone-specific deaths with those for Scotland's methadone-prescription clients.. The setting is all services in England that provide publicly-funded, structured treatment for illicit opioid users, the methodology linkage of the English National Drug Treatment Monitoring System and mortality database, and key measurements are DRDs, methadone-specific DRDs, or heroin-specific DRDs, by age-group and gender, with proportional hazards adjustment for substances used, injecting status and periods in/out of treatment.. Linkage was achieved for 129,979 adults receiving prescribing treatment modalities for opioid dependence during April 2005 to March 2009 and followed-up for 378,009 person-years (pys). There were 1,266 DRDs: 271 methadone-specific (7 per 10,000 pys: irrespective of gender) and 473 heroin-specific (15 per 10,000 pys for males, 7 for females). Methadone-specific DRD-rate per 10,000 person-years was 3.5 (95% CI: 2.7-4.4) at 18-34 years, 8.9 (CI: 7.3-10.5) at 35-44 years and 18 (CI: 13.8-21.2) at 45+ years; heroin-specific DRD-rate was unchanged with age. Relative to 25-34 years, pooled HRs for UK clients' methadone-specific deaths were: 0.87 at <25 years (95% CI: 0.56-1.35); 2.14 at 35-44 years (95% CI: 1.76-2.60); 3.75 at 45+ years (95% CI: 2.99-4.70).. International testing and explanation are needed of UK's sharp age-related increase in the risk of methadone-specific death. Clients should be alerted that their risk of methadone-specific death increases as they age.

Topics: Adolescent; Adult; Aging; Analgesics, Opioid; Databases, Factual; Female; Heroin; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Sex Factors; United Kingdom; Young Adult

Topics: Drug Overdose; Fentanyl; Heroin; Humans; Illicit Drugs; Opioid-Related Disorders; United States

Previous research has found diacetylmorphine, delivered under supervision, to be cost-effective in the treatment of severe opioid use disorder, but diacetylmorphine is not available in many settings. The Study to Assess Long-term Opioid Maintenance Effectiveness (SALOME) randomized controlled trial provided evidence that injectable hydromorphone is non-inferior to diacetylmorphine. The current study aimed to compare the cost-effectiveness of hydromorphone directly with diacetylmorphine and indirectly with methadone maintenance treatment.. A within-trial analysis was conducted using the patient level data from the 6-month, double-blind, non-inferiority SALOME trial. A life-time analysis extrapolated costs and outcomes using a decision analytical cohort model. The model incorporated data from a previous trial to include an indirect comparison to methadone maintenance.. A supervised clinic in Vancouver, British Columbia, Canada.. A total of 202 long-term street opioid injectors who had at least two attempts at treatment, including one with methadone (or other substitution), were randomized to hydromorphone (n = 100) or diacetylmorphine (n = 102).. We measured the utilization of drugs, visits to health professionals, hospitalizations, criminal activity, mortality and quality of life. This enabled us to estimate incremental costs, quality-adjusted life years (QALYs) and cost-effectiveness ratios from a societal perspective. Sensitivity analyses considered different sources of evidence, assumptions and perspectives.. The within-trial analysis found hydromorphone provided similar QALYs to diacetylmorphine [0.377, 95% confidence interval (CI) = 0.361-0.393 versus 0.375, 95% CI = 0.357-0.391], but accumulated marginally greater costs [$49 830 ($28 401-73 637) versus $34 320 ($21 780-55 998)]. The life-time analysis suggested that both diacetylmorphine and hydromorphone provide more benefits than methadone [8.4 (7.4-9.5) and 8.3 (7.2-9.5) versus 7.4 (6.5-8.3) QALYs] at lower cost [$1.01 million ($0.6-1.59 million) and $1.02 million ($0.72-1.51 million) versus $1.15 million ($0.71-1.84 million)].. In patients with severe opioid use disorder enrolled into the SALOME trial, injectable hydromorphone provided similar outcomes to injectable diacetylmorphine. Modelling outcomes during a patient's life-time suggested that injectable hydromorphone might provide greater benefit than methadone alone and may be cost-saving, with drug costs being offset by costs saved from reduced involvement in criminal activity.

Topics: British Columbia; Cost-Benefit Analysis; Crime; Double-Blind Method; Equivalence Trials as Topic; Health Services; Heroin; Hospitalization; Humans; Hydromorphone; Methadone; Mortality; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Severity of Illness Index

Employment is one of the less studied but a significant outcome of medication-assisted treatment. Thus, we aimed to explore employment outcomes of medication-assisted treatment with hydromorphone (HDM) or diacetylmorphine (DAM). The secondary aim was to estimate characteristics of this population as well as treatment-related factors associated with these outcomes.. This was a secondary analysis of a randomized, double blind controlled trial. A total of 102 and 100 participants were randomized to receive injectable DAM or HDM for 6 months respectively. In stage 2, 144 participants were randomized again to receive either oral or injectable forms of the medication they received for another 6 months. Participants were interviewed at 5 timepoints: before and 3, 6, 9 and 12 months after treatment assignment. Generalized estimating equations (GEE) with a logit link was fitted to determine factors related to paid work in the past 30 days.. Mean age of participants was 44.3 (SD = 9.6) and 59 (29.2%) participants were men. At each timepoint, 6-8 (3.6%-4.1%) participants reported employment in the past 30 days and 40 to 52 (19.7%-26.7%) reported minimum 1 day of paid work. University or college education [OR = 2.12: 95% CI = (1.25, 3.62), P = 0.01] was significantly associated with paid work after adjustment for age, gender, treatment arms, timepoints, days receiving study treatment, physical health, psychological health and crack cocaine use in the past 30 days.. The rate of employment was lower among participants of this study compared to similar studies on heroin-assisted treatment. Higher education was associated with increased odds of paid work. A large gap exists between employment rate and the proportion of participants who reported paid work. Supported employment and occupational therapy could optimize the employment outcomes of this population.

Topics: Adult; Double-Blind Method; Educational Status; Employment; Female; Heroin; Humans; Hydromorphone; Male; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Topics: Analgesics, Opioid; Continuity of Patient Care; Drug Overdose; Emergency Service, Hospital; Heroin; Humans; Opioid-Related Disorders; Referral and Consultation; United States

Topics: Cost-Benefit Analysis; Heroin; Humans; Hydromorphone; Methadone; Opioid-Related Disorders

A substantial proportion of individuals involved with the North American criminal justice system are convicted for drug-related activities. Drug treatment court (DTC) programs were developed as an alternative to incarceration for drug-related offences and aim to prioritize addiction treatment and improve health and social outcomes; however, only a fraction of DTC participants have access to first-line medications for opioid use disorder (OUD). Further, despite emerging evidence for the efficacy of injectable opioid agonist therapy (OAT) in treating individuals with severe OUD where past treatment attempts with first-line therapies have been unsuccessful, this treatment has never, to our knowledge, been implemented in correctional settings.. An individual in their 50s with a history of severe OUD, multiple interactions with the criminal justice system, and prior unsuccessful treatment attempts with methadone was initiated on injectable treatment with diacetylmorphine. The patient received 300 mg of diacetylmorphine witnessed 3 times daily at a supervised injection clinic. During a 1.5-year stabilization phase, the patient's illicit opioid use significantly reduced. They subsequently enrolled in a DTC program for drug-related charges preceding initiation on injectable OAT and remained on this therapy during 16 months in DTC. Following graduation from DTC, the patient continued to receive treatment and returned to gainful employment in the community, with no further charges or episodes of incarceration.. This case describes the successful completion of a DTC program by an individual prescribed injectable OAT for severe OUD. The patient's treatment plan played an integral role in DTC graduation and long-term adherence, leading to improved health and social outcomes, including cessation of illicit drug use, enhanced quality of life, and improved social functioning. The case highlights the potential benefits of a stepped and integrated approach to addiction treatment in DTC programs.

Topics: Administration, Intravenous; Heroin; Humans; Mandatory Programs; Middle Aged; Opioid-Related Disorders

To examine drug use behavior of clients attending Methadone Maintenance Treatment (MMT) programs and its relationship with the clients' social network characteristics.. Cross-sectional study.. Four MMT clinics in Kunming, Yunnan province, China.. 324 consecutive MMT clients.. A structured, self-completed questionnaire on background characteristics and existing social network. Current drug use was assessed by urine test for opiate metabolites.. The association between client's social network characteristics and their own current drug use behavior is analysed using multiple logistic regression adjusting for socio-demographic characteristics. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) are obtained to give the strength of the associations.. MMT clients were more likely to concurrently use heroin while attending MMT if their social network had any of the following characteristics: more than half of the members were older than them (AOR = 1.03, 95% CI = 1.00,1.06), any member had a high level of influence on them (AOR = 6.47, 95% CI = 2.86,14.65) and any member joined them in using drugs (AOR = 1.94, 95% CI = 1.04,3.63). Having a social network member who could provide emotional support (AOR = 0.11, 95% CI = 0.03,0.35), having a spouse and/or child in their social network (AOR = 0.44, 95% CI = 0.24,0.81) and having a social network member with a high level of closeness (AOR = 0.28, 95% CI = 0.09,0.90) were associated with a decreased odds of heroin use.. Social networks who could provide MMT clients with emotional support and a close relationship were significant factors for reducing the risk of concurrent drug use among clients attending MMT clinics in Kunming, China. Behavioral interventions should address the role of family and social network members in providing support to these clients.

Topics: Adult; China; Cross-Sectional Studies; Female; Heroin; Humans; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; Social Networking; Treatment Adherence and Compliance

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

Substantial use of the plant kratom for psychoactive effects has driven interest in its abuse liability. Several place conditioning studies suggest abuse liability of the active ingredient mitragynine, though studies of its self-administration have not been published.. Binding of mitragynine to rat brain mu, kappa, and delta opioid receptors was compared to that for heroin and morphine. Self-administration of mitragynine, heroin, methamphetamine, or saline was assessed during single-session substitutions in rats trained to self-administer methamphetamine (0.022 mg/kg/injection, i.v.) during 1-h daily sessions.. Mitragynine had > 2- or ~ 16-fold greater affinity for the mu opioid receptor than, respectively, for kappa or delta opioid receptors. Its affinity for the mu receptor was ~ 200-fold less than that for morphine. In rats trained to self-administer methamphetamine, saline substitutions significantly decreased the number of responses, whereas different doses of methamphetamine (0.002-0.068 mg/kg/injection) or heroin (0.001-0.03 mg/kg/injection) maintained self-administration with maximal responding at 0.022 or 0.01 mg/kg/injection, respectively. In contrast, no dose of mitragynine maintained response rates greater than those obtained with saline. Presession mitragynine treatment (0.1 to 3.0 mg/kg) decreased response rates maintained by heroin but had little effect on responding maintained by methamphetamine across the same range of doses.. These results suggest a limited abuse liability of mitragynine and potential for mitragynine treatment to specifically reduce opioid abuse. With the current prevalence of opioid abuse and misuse, it appears currently that mitragynine is deserving of more extensive exploration for its development or that of an analog as a medical treatment for opioid abuse.

Topics: Animals; Dose-Response Relationship, Drug; Heroin; Male; Morphine; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, mu; Secologanin Tryptamine Alkaloids; Self Administration

The opioid epidemic has been called the "most consequential preventable public health problem in the United States." Though there is wide recognition of the role of prescription opioids in the epidemic, evidence has shown that heroin and synthetic opioids contribute to the majority of opioid overdose deaths. It is essential to reframe the preventive strategies in place against the opioid crisis with attention to factors surrounding the illicit use of fentanyl and heroin. Data on opioid overdose deaths shows 42,000 deaths in 2016. Of these, synthetic opioids other than methadone were responsible for over 20,000, heroin for over 15,000, and natural and semi-synthetic opioids other than methadone responsible for over 14,000. Fentanyl deaths increased 520% from 2009 to 2016 (increased by 87.7% annually between 2013 and 2016), and heroin deaths increased 533% from 2000 to 2016. Prescription opioid deaths increased by 18% overall between 2009 and 2016. The Drug Enforcement Administration (DEA) mandated reductions in opioid production by 25% in 2017 and 20% in 2018. The number of prescriptions for opioids declined significantly from 252 million in 2013 to 196 million in 2017 (9% annual decline over this period), falling below the number of prescriptions in 2006. In addition, data from 2017 shows significant reductions in the milligram equivalence of morphine by 12.2% and in the number of patients receiving high dose opioids by 16.1%. This manuscript describes the escalation of opioid use in the United States, discussing the roles played by drug manufacturers and distributors, liberalization by the DEA, the Food and Drug Administration (FDA), licensure boards and legislatures, poor science, and misuse of evidence-based medicine. Moreover, we describe how the influence of pharma, improper advocacy by physician groups, and the promotion of literature considered peer-reviewed led to the explosive use of illicit drugs arising from the issues surrounding prescription opioids.This manuscript describes a 3-tier approach presented to Congress. Tier 1 includes an aggressive education campaign geared toward the public, physicians, and patients. Tier 2 includes facilitation of easier access to non-opioid techniques and the establishment of a National All Schedules Prescription Electronic Reporting Act (NASPER). Finally, Tier 3 focuses on making buprenorphine more available for chronic pain management as well as for medication-assisted treatment.. Opioid epidemic, fentanyl and heroin epidemic, prescription opioids, National All Schedules Prescription Electronic Reporting Act (NASPER), Prescription Drug Monitoring Programs (PDMPs).

Topics: Analgesics, Opioid; Drug Overdose; Epidemics; Fentanyl; Health Policy; Heroin; Humans; Illicit Drugs; Opioid-Related Disorders; United States; United States Food and Drug Administration

Despite promising findings of opioid overdose education and naloxone distribution (OEND) programs, overdose continues to be a major cause of mortality. The "cascade of care" is a tool for identifying steps involved in achieving optimal health outcomes. We applied the cascade concept to identify gaps in naloxone use.. Data came from a cross-sectional survey of 353 individuals aged 18 and older who self-reported lifetime history of heroin use.. The sample was majority male (65%) and reported use of heroin (74%) and injection (57%) in the past 6 months. Ninety percent had ever witnessed an overdose and of these 59% were in the prior year. Awareness of naloxone (90%) was high. Of those aware, over two-thirds reported having ever received (e.g. access) (69%) or been trained to use naloxone (60%). Of those who had ever received naloxone (n = 218) over one-third reported possession never (36%) or rarely/sometimes carrying naloxone (38%), while 26% reported always carrying. Nearly half of those who had ever received naloxone reported ever use to reverse an opiate overdose (45%). Among individuals who had ever received naloxone, possession often/always compared to never was associated with being female (RRR = 2.88, 95%CI = 1.31-6.27) and ever used naloxone during an overdose (RRR = 4.68, 95%CI = 2.00-11.0).. This study identifies that consistent possession is a gap in the naloxone cascade. Future research is needed to understand reasons for not always carrying naloxone.

Topics: Adolescent; Adult; Aged; Awareness; Cross-Sectional Studies; Drug Overdose; Female; Health Services Accessibility; Heroin; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Young Adult

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

British Columbia, Canada, is experiencing a public health emergency related to opioid overdoses driven by consumption of street drugs contaminated with illicitly manufactured fentanyl. This cross-sectional study evaluates a drug checking intervention for the clients of a supervised injection facility (SIF) in Vancouver.. Insite is a facility offering supervised injection services in Vancouver's Downtown East Side, a community with high levels of injection drug use and associated harms, including overdose deaths. During July 7, 2016, to June 21, 2017, Insite clients were offered an opportunity to check their drugs for fentanyl using a test strip designed to test urine for fentanyl. Results of the drug check were recorded along with information including the substance checked, whether the client intended to dispose of the drug or reduce the dose and whether they experienced an overdose. Logistic regression models were constructed to assess the associations between drug checking results and dose reduction or drug disposal. Crude odds ratios (OR) and 95% confidence intervals (CI) were reported.. About 1% of the visits to Insite during the study resulted in a drug check. Out of 1411 drug checks conducted by clients, 1121 (79.8%) were positive for fentanyl. Although most tests were conducted post-consumption, following a positive pre-consumption drug check, 36.3% (n = 142) of participants reported planning to reduce their drug dose while only 11.4% (n = 50) planned to dispose of their drug. While the odds of intended dose reduction among those with a positive drug check was significantly higher than those with a negative result (OR = 9.36; 95% CI 4.25-20.65), no association was observed between drug check results and intended drug disposal (OR = 1.60; 95% CI 0.79-3.26). Among all participants, intended dose reduction was associated with significantly lower odds of overdose (OR = 0.41; 95% CI 0.18-0.89).. Although only a small proportion of visits resulted in a drug check, a high proportion (~ 80%) of the drugs checked were contaminated with fentanyl. Drug checking at harm reduction facilities such as SIFs might be a feasible intervention that could contribute to preventing overdoses in the context of the current overdose emergency.

Topics: Analgesics, Opioid; British Columbia; Cross-Sectional Studies; Drug Contamination; Drug Overdose; Fentanyl; Harm Reduction; Heroin; Humans; Illicit Drugs; Naloxone; Narcotic Antagonists; Needle-Exchange Programs; Opioid-Related Disorders; Reagent Strips; Substance Abuse, Intravenous

Vaccines may offer a new treatment strategy for opioid use disorders and opioid-related overdoses. To speed translation, this study evaluates opioid conjugate vaccines containing components suitable for pharmaceutical manufacturing and compares analytical assays for conjugate characterization. Three oxycodone-based haptens (OXY) containing either PEGylated or tetraglycine [(Gly)

Topics: Adjuvants, Immunologic; Animals; Brain; Carrier Proteins; Disease Models, Animal; Drug Carriers; Drug Compounding; Drug Overdose; Haptens; Hemocyanins; Heroin; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nociception; Opioid-Related Disorders; Oxycodone; Tissue Distribution; Vaccines, Conjugate

Non-medical prescription opioid use (NMPOU) has become a major public health issue in the USA and is also increasing in Europe. However, little is known about neuropsychological associations of NMPOU-specifically regarding social cognition, which is essential for social functioning and treatability of opioid dependence. Previous studies with heroin users and opioid-substituted patients reported deficits in various cognitive functions, but these results are likely confounded by comorbid physical and psychiatric diseases, overdose-associated hypoxia, and adulteration of street heroin. Therefore, the purpose of the present study was to investigate social and non-social cognition in a relatively pure NMPOU sample taking opioid analgesics or antitussives.. We assessed 23 individuals with NMPOU objectively confirmed by hair analyses and 29 opioid-naïve, healthy controls, employing a comprehensive neuropsychological test battery.. Significant impairments were found between NMPOU individuals and controls regarding the cognitive domains of attention (p < .01, Hedge's g = .85), declarative memory (p < .05, g = .66), and global cognitive empathy (p < .01, g = 0.99)-the latter included problems with emotion recognition from faces, voices, and complex scenes. Opioid hair concentrations transformed to morphine equivalents were negatively correlated with global cognitive empathy (r = - 0.52, p < .01), suggesting dose-dependent deficits.. In contrast to stimulant users primarily displaying deficits in emotional empathy, opioid users showed relatively selective impairments in measures of cognitive empathy, with dose-dependent effects suggesting potential opioid-induced deficits and involvement of the opioid-system in processes of cognitive empathy. These results have important implications for future interventions of opioid dependence targeting social functioning and consequently enhancing therapy outcome and preventing relapse.

Topics: Adolescent; Adult; Analgesics, Opioid; Cognition; Empathy; Female; Heroin; Humans; Male; Morphine; Neuropsychological Tests; Opioid-Related Disorders; Social Behavior; Substance-Related Disorders; Young Adult

The overdose epidemic has been exacerbated by a dramatic increase in deaths involving illicitly manufactured fentanyl (IMF). Drug checking is a novel strategy to identify IMF in illicit drugs. We examined the uptake and acceptability of rapid fentanyl test strips among young adults.. From May to September 2017, we recruited 93 young adults in Rhode Island who reported injecting drugs or using heroin, cocaine, or illicitly obtained prescription pills in the past 30 days. Participants were asked to test either their urine after drug use (post-consumption) or a drug sample prior to use (pre-consumption) using rapid fentanyl test strips. After a questionnaire and a brief training, participants received ten strips for their personal use and were asked to return for a one-month follow-up visit, which assessed the uptake and acceptability of the rapid strips tests and the behavioral outcomes associated with receipt of a positive test.. Of the 81 (87%) participants who returned for follow-up and who had complete data, the mean age was 27, 45 (56%) were male, and 37 (46%) were non-white. A total of 62 participants (77%) reported using at least one test strip. Of these, 31 (50%) received at least one positive result. A positive result was associated with older age, homelessness, heroin use, injection drug use, ever witnessing an overdose, and concern about overdose or drugs being laced with fentanyl (all p < 0.05). Receiving a positive result was significantly associated with reporting a positive change in overdose risk behavior between baseline and follow-up (p ≤  0.01). Among all participants, 79 (98%) reported confidence in their ability to use the test strips and 77 (95%) wanted to use them in the future.. Young adults reported high uptake and acceptability of fentanyl test strips to detect IMF in illicit drugs.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Opioid-Related Disorders; Reagent Strips; Rhode Island; Risk-Taking; Substance Abuse, Intravenous; Surveys and Questionnaires; Young Adult

Adulteration of illicit drug supplies with synthetic opioids such as fentanyl has contributed to a dramatic rise in overdose morbidity and mortality in North America. One promising response to this crisis is the implementation of "drug checking" services. Drug checking encompasses a range of interventions used to assess the constituents of illicit drug samples, such as colour-spot testing, gas or liquid chromatography, and various methods of spectroscopy. Testing may be performed on-site at events or harm reduction service locales, performed independently by consumers, or sent to a centralized lab for analysis. This information may then serve to inform individual decision-making, enhance harm reduction efforts and strengthen public health surveillance and response strategies to prevent harms associated with illicit drug use. Historical examples of drug checking services that emerged with the 1990s synthetic "party drug" movement in Europe provide a theoretical and practical basis for the adaptation of these services for use in context of the current opioid overdose crisis. Potential harm reduction benefits of drug checking for synthetic opioid adulterants include individuals being more likely to use drugs more safely or to dispose of drugs found to contain harmful adulterants. Public health benefits of drug checking may also include negative feedback on the illicit drug supply with decreased availability or consumption of drugs from sources adulterated with synthetic opioids following public health warning campaigns. As part of the response to the current synthetic opioid epidemic in BC, pilot efforts are being undertaken in Vancouver to determine the feasibility and effectiveness of drug checking as an overdose response strategy. Models of drug checking service delivery and comparison of differing technologies, including unique challenges and potential solutions related to access to these services, legal obstacles, and sensitivity and specificity of testing technologies, are explored, alongside suggestions for future research and directions.

Topics: Analgesics, Opioid; Drug Contamination; Drug Overdose; Fentanyl; Harm Reduction; Heroin; Humans; Illicit Drugs; Opioid-Related Disorders

Civil commitment is an increasingly used policy intervention to combat the opioid epidemic. Yet little is known about persons who get committed and outcomes following commitment for opioid use. In the current cross-sectional study, we compared the characteristics of persons with and without a history of civil commitment, and the correlates of post-commitment abstinence.. Between October 2017 and May 2018, we surveyed consecutive persons entering a brief, inpatient opioid detoxification (n = 292) regarding their lifetime experiences with civil commitment for opioid use.. Participants averaged 34.6 years of age, 27.1% were female, and 78.1% were White. Seventy-eight (26.7%) experienced civil commitment for opioid use at least once in their lifetime. Committed individuals had significantly higher rates of fentanyl, heroin, and injection drug use, drug overdoses, past incarceration, current criminal justice involvement, and past medication treatment for opioid use (p < .05). The average time to relapse following commitment was 72 days, although 33.8% relapsed on the same day of their release. Longer post-commitment abstinence was significantly associated with post-commitment medication treatment, higher perceived procedural justice (i.e., fairness) during the commitment hearing, positive attitude and higher motivation at the end of commitment, and improvement in attitude during commitment (p < .05).. Opioid users who experience civil commitment constitute an especially high risk group. A positive commitment experience and post-commitment medication treatment are associated with longer post-commitment abstinence.

Topics: Adult; Analgesics, Opioid; Cross-Sectional Studies; Drug Overdose; Female; Fentanyl; Heroin; Humans; Inpatients; Male; Middle Aged; Opioid-Related Disorders; Prevalence; Residential Treatment; Substance Abuse, Intravenous; Surveys and Questionnaires

Older adults with opioid use disorder (OUD) are a medically complex population. The current study evaluated trends in older adults seeking treatment for OUD, with a focus on primary heroin versus prescription opioid use. This study also compared older adults with OUD to the younger OUD population on demographics and drug use behaviors.. Publicly available data from state-certified addiction treatment centers were collected via the Treatment Episode Data Set - Admissions (TEDS-A) between 2004-2015. This study utilized Joinpoint Regression to conduct a cross-sectional, longitudinal analysis of trends in first-time treatment admissions for OUD in adults 55 and older (older adults; n = 400,421) versus adults under the age of 55 (n = 7,795,839). Given the rapid increase in older adults seeking treatment for OUD between 2013-2015, secondary outcomes include changes in demographics and drug use between 2012 (as a baseline year) and 2015.. The proportion of older adults seeking treatment for OUD rose steadily between 2004-2013 (41.2% increase; p-trend = 0.046), then rapidly between 2013-2015 (53.5% increase; p-trend = 0.009). The proportion of older adults with primary heroin use more than doubled between 2012-2015 (p < 0.001); these individuals were increasingly male (p < 0.001), African American (p < 0.001), and using via the intranasal route of administration (p < 0.001).. There has been a recent surge in older adults seeking treatment for OUD, particularly those with primary heroin use. Specialized treatment options for this population are critically needed, and capacity for tailored elder care OUD treatments will need to increase if these trends continue.

Topics: Age Factors; Aged; Cross-Sectional Studies; Female; Heroin; Hospitalization; Humans; Male; Middle Aged; Opioid-Related Disorders; Sex Factors

Opioids are widely used for treating different types of pains, but overuse and abuse of prescription opioids have led to opioid epidemic in the United States. Besides analgesic effects, chronic use of opioid can also cause tolerance, dependence, and even addiction. Effective treatment of opioid addiction remains a big challenge today. Studies on addictive effects of opioids focus on striatum, a main component in the brain responsible for drug dependence and addiction. Some transcription regulators have been associated with opioid addiction, but relationship between analgesic effects of opioids and dependence behaviors mediated by them at the molecular level has not been thoroughly investigated. In this paper, we developed a new computational strategy that identifies novel targets and potential therapeutic molecular compounds for opioid dependence and addiction. We employed several statistical and machine learning techniques and identified differentially expressed genes over time which were associated with dependence-related behaviors after exposure to either morphine or heroin, as well as potential transcription regulators that regulate these genes, using time course gene expression data from mouse striatum. Moreover, our findings revealed that some of these dependence-associated genes and transcription regulators are known to play key roles in opioid-mediated analgesia and tolerance, suggesting that an intricate relationship between opioid-induce pain-related pathways and dependence may develop at an early stage during opioid exposure. Finally, we determined small compounds that can potentially target the dependence-associated genes and transcription regulators. These compounds may facilitate development of effective therapy for opioid dependence and addiction. We also built a database (http://daportals.org) for all opioid-induced dependence-associated genes and transcription regulators that we discovered, as well as the small compounds that target those genes and transcription regulators.

Topics: Analgesics, Opioid; Animals; Corpus Striatum; Gene Expression Regulation; Gene Ontology; Heroin; Machine Learning; Mice; Morphine; Neurons; Opioid-Related Disorders; Small Molecule Libraries

Based on the development of heroin vaccine, in this paper, we propose an age structured heroin transmission model with treatment and vaccination. The model allows the drug reuse rate of the individuals in treatment to depend on a treatment-age and the vaccine waning rate of the vaccinated to depend on a vaccination age. Meanwhile, the model allows that the heroin vaccine provides an imperfect protection (i.e., the vaccinated individuals can also become drug addicted). We derive the basic reproduction number which dependents on vaccination. The basic reproduction number completely determines the persistence and extinction of heroin spread, i.e., if the basic reproduction number is less than one the drug-free steady state is globally asymptotically stable (i.e., the heroin spread dies out), if the basic reproduction number is larger than one, there exists an unique positive steady state and it is locally and globally stable in some special cases. Finally, some numerical simulations are carried out to illustrate the stability of the positive steady state.

Topics: Age Factors; Basic Reproduction Number; Computer Simulation; Heroin; Humans; Immunization Programs; Models, Biological; Opioid-Related Disorders; Treatment Outcome; Vaccination; Vaccines

Topics: Centers for Disease Control and Prevention, U.S.; China; Crime; Drug Overdose; Federal Government; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Ohio; Opiate Alkaloids; Opioid-Related Disorders; United States

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

Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence. All substrains exhibited a dose-dependent increase in oral oxycodone and heroin preference and intake under limited-access procedures and all, but 129S1/SvlmJ mice, exhibited oxycodone reinforcement. Relative to the other substrains, 129P3/J mice exhibited higher heroin and oxycodone intake. While 129X1/SvJ exhibited the highest anxiety-like behavior during natural opioid withdrawal, somatic and behavior signs of precipitated withdrawal were most robust in 129P3/J mice. These results demonstrate the feasibility and relative sensitivity of our oral opioid self-administration procedures for detecting substrain differences in drug reinforcement/intake among 129 mice, of relevance to the identification of genetic variants contributing to high vs. low oxycodone reinforcement and intake.

Topics: Analgesics, Opioid; Animals; Fentanyl; Genetic Variation; Heroin; Male; Mice; Opioid-Related Disorders; Oxycodone; Reinforcement, Psychology; Substance Withdrawal Syndrome

This the first 5-year effectiveness study of publicly funded treatment for opioid use disorder (OUD) in England.. All adults initiating treatment in 2008/09 in all 149 local treatment systems reporting to the National Drug Treatment Monitoring System (n=54,347). Admission polydrug use sub-populations were identified by Latent Class Analysis. The treatment outcome measure was 'successful completion and no re-presentation within six months' (SCNR) analysed by multilevel, multivariable logistic regression and funnel plots to contrast outcome by treatment system.. SCNR was achieved by 21.9%. Heroin and crack cocaine users were significantly less likely to achieve this outcome than patients who used heroin only (adjusted odds ratio [AOR] 0.90; 95% confidence interval [CI] 0.85-0.95). Older patients (AOR 1.09; CI 1.07-1.11), those employed (AOR 1.27; CI 1.18-1.37) and those enrolled for longer treatment were more likely to achieve the outcome measure. After risk adjustment, the local treatment systems that achieved substantially better outcome performance (14/149) had a lower rate of opiate prevalence in the local population at time of study initiation (incidence rate difference [IRD] 4.1; CI 4.0-4.2), fewer criminal offences per thousand (IRD 28.5; CI 28.1-28.8) and lower drug-related deaths per million (IRD 5.9; CI 5.9-5.9).. In an English national study, one fifth of patients successful completed treatment for OUD and did not present for further treatment within six months. Longer time in treatment increases the probability of achieving and maintaining clinical benefit from treatment. After risk-adjustment, an important minority of treatment systems achieve substantially better outcome performance.

Topics: Adult; Analgesics, Opioid; Crack Cocaine; England; Female; Heroin; Hospitalization; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Substance Abuse Treatment Centers; Treatment Outcome

Given the relatively recent growth in access to heroin and a more permissive atmosphere surrounding its use, we hypothesized that an increasing number of persons with limited experience and tolerance to opioids would experiment with heroin as their first opioid rather than more common prescription opioid analgesics.. Individuals entering substance abuse treatment for an opioid use disorder in the period 2010-2016 (N=5885) were asked about the specific opioid they first regularly used to get high. To limit long-term recall and survival bias, analyses was restricted to opioid initiation that occurred in the past ten years (2005-2015).. In 2005, only 8.7% of opioid initiators started with heroin, but this sharply increased to 33.3% (p<0.001) in 2015, with no evidence of stabilization. The use of commonly prescribed opioids, oxycodone and hydrocodone, dropped from 42.4% and 42.3% of opioid initiators, respectively, to 24.1% and 27.8% in 2015, such that heroin as an initiating opioid was now more frequently endorsed than prescription opioid analgesics.. Our data document that, as the most commonly prescribed opioids - hydrocodone and oxycodone - became less accessible due to supply-side interventions, the use of heroin as an initiating opioid has grown at an alarming rate. Given that opioid novices have limited tolerance to opioids, a slight imprecision in dosing inherent in heroin use is likely to be an important factor contributing to the growth in heroin-related over dose fatalities in recent years.

Topics: Adult; Analgesics, Opioid; Female; Heroin; Humans; Male; Opioid-Related Disorders; United States

Heroin and fentanyl use have reached epidemic proportions in the United States and are now blamed for the majority of drug-related overdose deaths. Both drugs are produced primarily in South America and Asia and enter the United States illegally. One result of smoking or injecting heroin or fentanyl is the development of a substance use disorder (SUD), which causes changes in brain chemistry and function. These changes result in negative behaviors and an inability to stop use. Yet, treatments are available and recovery is possible. Nurses have the potential to impact the heroin and fentanyl epidemic through developing therapeutic relationships with patients who are at risk or already have a SUD. Strategies for effective communication include maintaining a supportive, nonjudgmental attitude and incorporating motivational interviewing. All patients should be screened for opioid use and referred for treatment if indicated. It is important for nurses to be knowledgeable about heroin and fentanyl and available treatments. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 16-20.].

Topics: Drug Overdose; Fentanyl; Heroin; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Nurse-Patient Relations; Opioid-Related Disorders; Substance-Related Disorders; United States

Topics: Analgesics, Opioid; Heroin; Humans; Opioid-Related Disorders; Prospective Studies; Veterans

The dopamine (DA) D3 receptor (D3R) is highly expressed in the basolateral nucleus of the amygdala (BLA), a neural region critical for processing opiate-related reward and withdrawal aversion-related memories. Functionally, D3R transmission is linked to downstream Cdk5 and calcineurin signaling, both of which regulate D3R activity states and play critical roles in memory-related synaptic plasticity. Previous evidence links D3R transmission to opiate-related memory processing, however little is known regarding how chronic opiate exposure may alter D3R-dependent memory mechanisms. Using conditioned place preference (CPP) and withdrawal aversion (conditioned place aversion; CPA) procedures in rats, combined with molecular analyses of BLA protein expression, we examined the effects of chronic opiate exposure on the functional role of intra-BLA D3R transmission during the acquisition of opiate reward or withdrawal aversion memories. Remarkably, we report that the state of opiate exposure during behavioural conditioning (opiate-naïve/non-dependent vs. chronically exposed and in withdrawal) controlled the functional role of intra-BLA D3R transmission during the acquisition of both opiate reward memories and withdrawal-aversion associative memories. Thus, whereas intra-BLA D3R blockade had no effect on opiate reward memory formation in the non-dependent state, blockade of intra-BLA D3R transmission prevented the formation of opiate reward and withdrawal aversion memory in the chronically exposed state. This switch in the functional role of D3R transmission corresponded to significant increases in Cdk5 phosphorylation and total expression levels of calcineurin, and a corresponding decrease in intra-BLA D3R expression. Inhibition of either intra-BLA Cdk5 or calcineurin reversed these effects, switching intra-BLA associative memory formation back to a D3R-independent mechanism.

Topics: Analgesics, Opioid; Animals; Association Learning; Avoidance Learning; Basolateral Nuclear Complex; Calcineurin; Conditioning, Psychological; Cyclin-Dependent Kinase 5; Disease Models, Animal; Heroin; Male; Memory; Opioid-Related Disorders; Ranolazine; Rats, Sprague-Dawley; Receptors, Dopamine D3; Reward; Signal Transduction; Spatial Behavior; Substance Withdrawal Syndrome

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

There are limited data about the extent of DSM-5 substance use disorders (SUDs) among primary care patients.. This study analyzed data from a multisite validation study of a substance use screening instrument conducted in a diverse sample of 2000 adults aged ≥18 years recruited from five primary care practices in four states. Prevalence and correlates of 12-month DSM-5 SUDs were examined.. Overall, 75.5% of the sample used any substance, including alcohol (62.0%), tobacco (44.1%), or illicit drugs/nonmedical medications (27.9%) in the past 12 months (marijuana 20.8%, cocaine 7.3%, opioids 4.8%, sedatives 4.1%, heroin 3.9%). The prevalence of any 12-month SUD was 36.0% (mild disorder 14.2%, moderate/severe disorder 21.8%): tobacco 25.3% (mild 11.5%, moderate/severe 13.8%); alcohol 13.9% (mild 6.9%, moderate/severe 7.0%); and any illicit/nonmedical drug 14.0% (mild 4.0%, moderate/severe 10.0%). Among past 12-month users, a high proportion of tobacco or drug users met criteria for a disorder: tobacco use disorder 57.4% (26.1% mild, 31.3% moderate/severe) and any drug use disorder 50.2% (14.3% mild, 35.8% moderate/severe); a lower proportion of alcohol users (22.4%) met criteria for alcohol use disorder (11.1% mild, 11.3% moderate/severe). Over 80% of adults with opioid/heroin use disorder met criteria for a moderate/severe disorder. Younger ages, male sex, and low education were associated with increased odds of having SUD.. These findings reveal the high prevalence of SUDs in primary care and underscore the need to identify and address them.

Topics: Adult; Alcoholism; Cannabis; Diagnostic and Statistical Manual of Mental Disorders; Heroin; Humans; Hypnotics and Sedatives; Illicit Drugs; Opioid-Related Disorders; Prevalence; Primary Health Care; Substance-Related Disorders; Tobacco Use Disorder

Intolerance of uncertainty (IU) is the tendency to interpret ambiguous situations as threatening and having negative consequences, resulting in feelings of distress and anxiety. IU has been linked to a number of anxiety disorders, and anxiety felt in the face of uncertainty may result in maladaptive behaviors such as impulsive decision making. Although there is strong evidence that anxiety and impulsivity are risk factors for addiction, there is a paucity of research examining the role of IU in this disorder. The rate of opioid addiction, in particular, has been rising steadily in recent years, which necessitates deeper understanding of risk factors in order to develop effective prevention and treatment methods. The current study tested for the first time whether opioid-dependent adults are less tolerant of uncertainty compared to a healthy comparison group. Opioid dependent patients undergoing methadone maintenance therapy (n = 114) and healthy comparisons (n = 69) completed the following scales: Intolerance of Uncertainty Scale, the Barrett Impulsivity Scale, and the State Trait Anxiety Inventory. Analysis revealed that these measures were positively correlated with each other and that opioid-dependent patients had significantly higher IU scores. Regression analysis revealed that anxiety mediated the relationship between IU and impulsivity. Hierarchical moderation regression found an interaction between addiction status and impulsivity on IU scores in that the relationship between these variables was only observed in the patient group. Findings suggest that IU is a feature of addiction but does not necessarily play a unique role. Further research is needed to explore the complex relationship between traits and how they may contribute to the development and maintenance of addiction.

Topics: Adult; Analgesics, Opioid; Anxiety; Case-Control Studies; Decision Making; Female; Heroin; Humans; Impulsive Behavior; Male; Methadone; Middle Aged; Opioid-Related Disorders; Personality Inventory; Psychiatric Status Rating Scales; Regression Analysis; Risk Factors; Uncertainty

Nonmedical prescription opioid use (NMPOU) is well documented among participants in the club scene, yet prior studies have not examined transition to heroin use. We prospectively examined heroin initiation among a sample of young adults with drug involvement associated with participation in the club scene, to understand factors that influence transition from NMPOU to heroin and to identify opportunities for intervention.. Data were drawn from a randomized trial that enrolled 750 Miami-based club and prescription drug users through respondent driven sampling, and tested the efficacy of assessment interventions in reducing risk. Participants reported current substance use at baseline, 3, 6, and 12 month follow-ups. We examined predictors of heroin initiation among participants reporting NMPOU at baseline, with no lifetime history of heroin use (N=323).. The mean age was 25.0 years; 67.5% met DSM-IV criteria for substance dependence. About 1 in 13 participants (7.7%) initiated heroin use at follow-up. In univariable comparisons, frequent LSD use, history of drug overdose, high frequency NMPOU, using oral tampering methods, and endorsing a primary medical source for prescription opioids were associated with greater likelihood of heroin initiation. LSD use, oral tampering, and primary medical source were significant predictors in a Cox regression model.. Heroin initiation of 7.7% suggests a high level of vulnerability for transition among young adult NMPO users in the club scene. The importance of oral tampering methods in the trajectory of NMPOU may indicate a need to further examine the role of abuse deterrent formulations in prevention efforts.

Topics: Analgesics, Opioid; Diagnostic and Statistical Manual of Mental Disorders; Drug Overdose; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Prescriptions; Young Adult

Opioid use disorder is a growing epidemic, with an alarming number of associated deaths. In 2014, in the United States, 18,893 lethal overdoses were related to prescription opioids and 10,574 due to heroin. Despite the growing number of treatment options for substance use disorders, which are chronic, relapsing-remitting conditions, relapse rates remain as high as 91%. In the United States, 7.5 million children reside with at least one patient who abuses drugs or alcohol. Mothers are twice as likely to lose custody of their children. They have higher rates of comorbid abuse and psychopathology and limited social supports. Child service agencies, commonly involved in these scenarios, are often pressured to find permanent placement for children, within an expedited timeframe, inconsistent with the need for sufficient time for recovery and goals of family inclusion and unity. We present the complicated case of a 25-year-old woman with a history of opioid use disorder and depression, who, after being in and out of treatment programs for years, had a lethal overdose. She had a significant family history of addiction and had lost custody of her children. This challenging, but common presentation draws attention to challenges in providing treatment during this opioid epidemic.

Topics: Adult; Drug Overdose; Female; Heroin; Humans; Opioid-Related Disorders; United States

There has been international concern over the rise in fatal pharmaceutical opioid overdose rates, driven by increased opioid analgesic prescribing. The current study aimed to examine trends in opioid overdose deaths by: 1) opioid type (heroin and pharmaceutical opioids); and 2) age, gender, and intent of the death assigned by the coroner.. Analysis of data from the National Coronial Information System (NCIS) of opioid overdose deaths occurring between 2001 and 2012.. Deaths occurred predominantly (98%) among Australians aged 15-74 years. Approximately two-thirds of the decedents (68%) were male. The heroin overdose death rate remains unchanged over the period; these were more likely to occur among males. Pharmaceutical opioid overdose deaths increased during the study period (from 21.9 per million population in 2001-36.2), and in 2012 they occurred at 2.5 times the incident rate of heroin overdose deaths. Increases in pharmaceutical opioid deaths were largely driven by accidental overdoses. They were more likely to occur among males than females, and highest among Australians aged 45-54 years. Rates of fentanyl deaths in particular showed an increase over the study period (from a very small number at the beginning of the period) but in 2012 rates of morphine deaths were higher than those for oxycodone, fentanyl and tramadol.. Given the increase in rates of pharmaceutical opioid overdose deaths, it is imperative to implement strategies to reduce pharmaceutical opioid-related mortality, including more restrictive prescribing practices and increasing access to treatment for opioid dependence.

Topics: Analgesics, Opioid; Australia; Drug Overdose; Fentanyl; Heroin; Humans; Morphine; Opioid-Related Disorders; Oxycodone; Pharmaceutical Preparations; Tramadol

This study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects.. Heroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing and subjective effects of intravenous (IV) doses of Bup (1.51, 2.16, 6.15, and 8.64mg) and Bup/Nx (1.51/0.44, 2.16/0.61, 6.15/1.71, and 8.64/2.44mg). Placebo (Pbo), heroin (25mg) and Nx (0.3mg) were tested as neutral, positive, and negative controls, respectively.. IV Bup alone was self-administered substantially less than IV heroin, though the two largest doses of Bup produced positive subjective effects, drug "Liking" (0-100mm), which were comparable to heroin (mean difference: Heroin vs Bup 6.15mg: -3.4mm, Heroin vs Bup 8.64mg: -11.3mm). All indicators of abuse potential seen with IV Bup alone were substantially decreased with the addition of Nx. All Bup/Nx combinations produced ratings of aversive effects, "Bad", which were comparable to, or greater than IV, Nx. On three of the four measures of aversive effects, the largest difference is seen with the 8.64 vs 8.64/2.44 condition.. This study further demonstrates the ability of the Bup/Nx combination to deter IV use. Although none of the Bup/Nx combinations showed indications of abuse potential, formulations with larger absolute Nx, may be less abusable as they precipitate a greater degree of withdrawal.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Heroin; Humans; Injections, Intravenous; Naloxone; Opioid-Related Disorders; Reinforcement, Psychology

The use of prescription opioid analgesics, particularly oxycodone, has dramatically increased, and parallels escalated opioid abuse and drug-related deaths worldwide. Understanding the molecular mechanisms underlying the development of opioid dependence and expanding treatment options to counter prescription opioid abuse has become a critical public health matter. In the present study, we first evaluated the reinforcing effects of oxycodone in a rat model of self-administration and then explored the potential utility of two novel high affinity dopamine D3 receptor (D3R) antagonists/partial agonists, CAB2-015 and BAK4-54, for treatment of prescription opioid abuse and dependence. We found that rats acquired oxycodone self-administration rapidly within a range of unit doses that was similar to that for heroin, confirming that oxycodone has significant abuse potential. Strikingly, pretreatment with either CAB2-015 or BAK4-54 (0.4-10 mg/kg, i.p.) dose-dependently decreased oxycodone self-administration, and shifted the oxycodone dose-response curve downward. Repeated pretreatment with CAB2-015 or BAK4-54 (0.4-4 mg/kg) facilitated extinction and inhibited oxycodone-induced reinstatement of drug-seeking behavior. In addition, pretreatment with CAB2-015 or BAK4-54 (4-10 mg/kg) also dose-dependently decreased oxycodone-enhanced locomotor activity, but only CAB2-015 decreased oral sucrose self-administration. These data suggest that D3R antagonists may be suitable alternatives or adjunctive to opioid-based medications currently used clinically in treating opioid addiction and that the D3R-selective ligands (CAB2-015 or BAK4-54) provide new lead molecules for development.

Topics: Animals; Dose-Response Relationship, Drug; Drug Partial Agonism; Drug-Seeking Behavior; Extinction, Psychological; Heroin; Indoles; Male; Naphthalenes; Narcotics; Opioid-Related Disorders; Oxycodone; Piperazines; Quinolines; Rats, Long-Evans; Receptors, Dopamine D3; Self Administration

Topics: Analgesics, Opioid; Heroin; Humans; Opioid-Related Disorders; Prevalence; Surveys and Questionnaires

Supervised injectable opioid assisted treament (siOAT) prescribes injectable opioids to individuals for whom other forms of addiction treatment have been ineffective. In this article, we examine arguments that opioid-dependent people should be assumed incompetent to voluntarily consent to clinical research on siOAT unless proven otherwise. We agree that concerns about competence and voluntary consent deserve careful attention in this context. But we oppose framing the issue solely as a matter of the competence of opioid-dependent people and emphasize that it should be considered in the context of inequities in access to siOAT as a medical treatment. Consequently, we suggest that bioethics literature on nonexploitation, which focuses on clinical research in low-income countries, is helpful due to locating ethical issues within systemic social conditions. Finally, we consider the implications of our argument for the ethics of clinical research on siOAT.

Topics: Analgesics, Opioid; Clinical Trials as Topic; Heroin; Informed Consent; Mental Competency; Opioid-Related Disorders

The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis.. We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or levomethadone (n = 54) and similar levels in a healthy control group (n = 72).. There was a significantly higher methylation of VEGF-A in opioid-maintained patients with levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001).. The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.

Topics: Adult; Analgesics, Opioid; DNA Methylation; Epigenesis, Genetic; Female; Heroin; Humans; Male; Methadone; Nerve Growth Factor; Opioid-Related Disorders; Promoter Regions, Genetic; Vascular Endothelial Growth Factor A

Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = -0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck's Depression Inventory measurements (r = -0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. levomethadone with heroine co-use: p = 0.043, diamorphine vs. levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving levomethadone without heroine co-use (linear mixed model: control vs. levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in levomethadone maintenance treatment.

Topics: Adult; Analgesics, Opioid; Brain-Derived Neurotrophic Factor; Case-Control Studies; Depression; Epigenesis, Genetic; Female; Heroin; Humans; Male; Methadone; Methylation; Middle Aged; Opioid-Related Disorders; Promoter Regions, Genetic; Prospective Studies; Psychiatric Status Rating Scales; Statistics, Nonparametric; Surveys and Questionnaires; Visual Analog Scale

Relapse to opioids is often driven by the avoidance of the aversive states of opioid withdrawal. We recently demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. However, the role of PPARγ in withdrawal and other forms of relapse to heroin is unknown.. To further address this issue, we investigated the role of PPARγ on the development and expression of morphine withdrawal in mice and the effect of pioglitazone on several forms of heroin relapse in rats.. We induced physical dependence to morphine in mice by injecting morphine twice daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection of naloxone. In addition, different groups of rats were trained to self-administer heroin and, after the extinction, the relapse was elicited by cues, priming, or stress. The effect of different doses of pioglitazone was tested on these different paradigms.. Data show that chronic and acute administration of pioglitazone attenuates morphine withdrawal symptoms, and these effects are mediated by activation of PPARγ receptors. Activation of PPARγ by pioglitazone also abolishes yohimbine-induced reinstatement of heroin seeking and reduces heroin-induced reinstatement, while it does not affect cue-induced relapse.. These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals.

Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Conditioning, Operant; Heroin; Male; Mice; Morphine; Narcotics; Opioid-Related Disorders; Pioglitazone; Rats; Rats, Wistar; Recurrence; Rodentia; Self Administration; Substance Withdrawal Syndrome; Thiazolidinediones

The rate of overdose deaths caused by fentanyl-contaminated heroin (FCH) use is increasing rapidly in the United States. We examined risk factors for exposure to FCH and experiences with FCH use among young adult non-medical prescription opioids (NMPO) users.. We analyzed data from the Rhode Island Young Adult Prescription Drug Study (RAPiDS), which enrolled young adults aged 18 to 29 reporting prior 30day NMPO use between January 2015 and February 2016. Participants completed questionnaires ascertaining drug use patterns and risk behaviors, including FCH exposure. Logistic regression was used to assess factors associated with known or suspected FCH exposure.. Of 199 participants, the median age was 25 (IQR: 22, 27), 130 (65.3%) were male, and 122 (61.3%) were of White, non-Hispanic race/ethnicity. In total, 22 (11%) reported known or suspected FCH exposure in the prior six months. Several drug use patterns and risk behaviors were associated with FCH exposure, including: regular heroin and cocaine use; diverted pharmaceutical fentanyl use in the prior six months; NMPO use to avoid withdrawal symptoms; longer duration of NMPO use; regular injection drug use; and prior overdose (all p<0.001). Among participants who reported FCH exposure, 59% were unaware that their heroin was contaminated with fentanyl prior to last use, 59% reported that FCH provides a better high, and all recognized that fentanyl increases overdose risk.. Exposure to fentanyl-contaminated heroin is an emerging trend among young adult NMPO users in Rhode Island. Overdose prevention programs addressing FCH use are urgently needed.

Topics: Adult; Analgesics, Opioid; Female; Fentanyl; Health Knowledge, Attitudes, Practice; Heroin; Humans; Male; Opioid-Related Disorders; Pilot Projects; Prescription Drug Misuse; Prevalence; Rhode Island; Risk Factors; Risk-Taking; Surveys and Questionnaires; Young Adult

Topics: Analgesics, Opioid; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Veterans

Topics: Analgesics, Opioid; Heroin; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Veterans

The prevalence of opioid use in therapeutic and recreational settings has steadily increased throughout the western world. The addition of fentanyl into heroin products can produce potentially dangerous consequences, even to opioid tolerant individuals who may be unaware of such additions. Following an observed spike of heroin-fentanyl related deaths in Melbourne, Australia, a study was undertaken to determine the prevalence of these cases. All reportable deaths occurring in Victoria during 2015 and submitted to the toxicology laboratory were analysed using LC-MS-MS to confirm the combination of the heroin marker 6-acetylmorphine and/or morphine, and fentanyl. Over 4,000 coronial cases in 2015 underwent toxicological analysis for these drugs, there were nine cases identified that involved fentanyl-laced heroin. There was no specific mention of fentanyl use in any of these cases. All occurred within 2 months and in two distinct locations. The first four deaths occurred within 3 days of each other, in neighboring suburbs. The ages ranged from 25 to 57 years with an average of 40 and median of 37 years, and consisted of eight males and one female. The average and median femoral blood concentration of fentanyl was 18 and 20 ng/mL (range: <1-45 ng/mL), and morphine 140 and 80 ng/mL (range: 20-400 ng/mL), respectively. All nine cases had 6-acetylmorphine detectable in blood. Urine analysis was also performed where available. A syringe, powder and spoon found at the scene of one case were also analysed and found to be positive for both heroin and fentanyl, which supported the likelihood of fentanyl-laced heroin. This is the first reported case series of fatalities involving heroin and fentanyl outside of North America in published literature. These findings may help inform public health and prevention strategies serving to decrease the potential for such fatalities in the future.

Topics: Adult; Cause of Death; Drug Overdose; Female; Fentanyl; Forensic Toxicology; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Prevalence; Substance Abuse Detection; Victoria

Nonmedical use of opioids has become increasingly problematic in recent years with increases in overdoses, treatment admissions, and deaths. Use also appears to be contributing to heroin initiation, which has increased in recent years. Further research is needed to examine which adolescents are at highest risk for nonmedical use of opioids and heroin and to explore potential links between nonmedical opioid use and heroin use.. Data were analyzed from a nationally representative sample of American high school seniors in the Monitoring the Future study (2009-2013, Weighted N=67,822). We examined associations between frequency and recency of nonmedical use of opioids and heroin. Sociodemographic correlates of use of each drug were also examined.. 12.4% of students reported lifetime nonmedical opioid use and 1.2% reported lifetime heroin use. As frequency of lifetime nonmedical opioid use increased, so too did the odds for reporting heroin use, with over three-quarters (77.3%) of heroin users reporting lifetime nonmedical opioid use. Recent (30-day) nonmedical opioid use was a robust risk factor for heroin use and almost a quarter (23.2%) of students who reported using opioids ≥40 times reported lifetime heroin use. Black and Hispanic students were less likely to report nonmedical opioid or heroin use than white students, but they were more likely to report heroin use in absence of nonmedical opioid use.. Recent and frequent nonmedical opioid use are risk factors for heroin use among adolescents. Prevention needs to be targeted to those at highest risk.

Topics: Adolescent; Analgesics, Opioid; Cross-Sectional Studies; Female; Heroin; Humans; Male; Opioid-Related Disorders; Risk Factors; Schools; Students; United States; Young Adult

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

In October 2014, the Drug Enforcement Administration reclassified hydrocodone to schedule II, increasing regulations on use. The impact of rescheduling hydrocodone on opioid exposures is unclear, especially in states with special restrictions required for prescribing schedule II agents.. To assess whether changes in exposures to prescription opioid analgesics and heroin as reported to poison centers occurred in the 6 months after hydrocodone rescheduling. We hypothesized that hydrocodone exposures would decrease, while less tightly regulated opioids, such as codeine and tramadol, would increase.. This study compares opioid analgesic exposures reported to Texas Poison Centers before and after this change in a state that requires special prescription pads for Schedule II agents. Cases included all opioid analgesic exposures reported to a statewide poison center network, comparing exposures from 6 months before to 6 months after heightened regulations. Specific opioids with large changes in reported exposures were further characterized by patient age and exposure intent.. Hydrocodone exposures decreased from 1567 to 1135 (28%, p = 0.00017), decreasing for all ages. Codeine exposures increased significantly from 189 to 522 (176%, p = 0.00014), including a 263% increase for age >20 years. Codeine misuse increased 443% and adverse drug events 327%. Oxycodone exposures increased from 134 to 189 (39%, p = 0.0143), increasing only among patients age >20 years. Reported heroin exposures increased from 156 to 179 (15%, p = 0.2286) and tramadol from 666 to 708 (6%, p = 0.0193). Other opioid exposures changed little or had limited reports.. The increased regulation of hydrocodone was followed temporally by a decrease in reported hydrocodone exposures, but also increases in codeine, oxycodone and tramadol exposures. This may reflect a shift in prescribing practices, changes in street availability of hydrocodone or decreased drug diversion.. The increased regulation was temporally associated with decreased hydrocodone exposures reported to Texas Poison Centers.

Topics: Analgesics; Analgesics, Opioid; Codeine; Drug and Narcotic Control; Government Regulation; Heroin; Humans; Hydrocodone; Opioid-Related Disorders; Oxycodone; Poison Control Centers; Prescription Drug Misuse; Texas; Tramadol

Chronic opioid abusers are more susceptible to bacterial and viral infections, but the molecular mechanism underlying opioid-induced immunosuppression is unknown. MicroRNAs (miRNAs) are emerging as key players in the control of biological processes, and may participate in immune regulation. In this study, we investigated the molecular mechanisms in opioid-induced and miRNA-mediated immunosuppression, in the context of miRNA dysregulation in opioid abusers. Blood samples of heroin abusers were collected and analyzed using miRNA microarray analysis and quantitative PCR validation. The purified primary human monocytes were cultured in vitro to explore the underlying mechanism. We found that morphine and its derivative heroin significantly decreased the expression levels of miR-582-5p and miR-590-5p in monocytes. cAMP response element-binding protein 1 (CREB1) and CREB5 were detected as direct target genes of miR-582-5p and miR-590-5p, respectively, by using dual-luciferase assay and western bolt. Functional studies showed that knockdown of CREB1/CREB5 increased tumor necrosis factor alpha (TNF-α) level and enhanced expression of phospho-NF-κB p65 and NF-κB p65. Our results demonstrated that miR-582-5p and miR-590-5p play important roles in opioid-induced immunosuppression in monocytes by targeting CREB1/CREB5-NF-κB signaling pathway.

Topics: Adult; Analgesics, Opioid; Blotting, Western; Case-Control Studies; Cyclic AMP Response Element-Binding Protein; Cyclic AMP Response Element-Binding Protein A; Female; Heroin; Humans; Immunologic Deficiency Syndromes; In Vitro Techniques; Interleukin-10; Male; MicroRNAs; Middle Aged; Monocytes; Morphine; NF-kappa B; Opioid-Related Disorders; Phosphoproteins; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Young Adult

Polymorphisms in genes such as DAT1, 5HTTLPR, D4DR4, and MAO-A have been linked to attention deficit hyperactivity disorder (ADHD) and susceptibility for opiate addiction. We investigated in opiate-addicted parents and their children the rate of ADHD and genetic markers that could predict susceptibility to ADHD and/or opiate addiction.. We studied 64 heroin-addicted, methadone-maintained parents, and their 94 children who had or had not been exposed prenatally to opiates. DNA extracted from mouthwash was assessed for genetic polymorphism for six polymorphic sites of four different genes. Study subjects also filled a variety of questionnaires assessing the rate of ADHD in the parents and children and the children's intelligence quotient.. Children of opiate-dependent mothers had a higher rate of ADHD compared to those of the opiate-dependent fathers. Opiate-dependent parents have a high risk of being carriers of most risk alleles examined except DRD4EX3 (allele 7). There was no difference whether the addicted parents had or did not have ADHD.. Serotonergic and dopaminergic risk alleles seem to be mainly related to opiate dependence with no effect on the occurrence of ADHD. People carrying those polymorphisms are susceptible to opioid addiction and not necessarily to ADHD.

Topics: Adolescent; Alleles; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Heroin; Humans; Male; Methadone; Opioid-Related Disorders; Parents; Polymorphism, Genetic; Pregnancy; Prenatal Exposure Delayed Effects; Sequence Analysis, DNA; Surveys and Questionnaires

Topics: Analgesics, Opioid; Drug Overdose; Heroin; Humans; Legislation, Drug; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Prescription Drugs; United States

Topics: Germany; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Selection; Substance Abuse, Intravenous

Topics: Adult; Female; France; Heroin; Humans; Hypertension, Pulmonary; Incidence; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Risk Factors

Topics: Half-Life; Heroin; Humans; Naloxone; Opioid-Related Disorders; Prodrugs; Time Factors

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

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

Prescription opioid (PO) injection among people who use illicit drugs (PWUD) is an ongoing concern, yet little is known about drug use trajectories associated with initiating PO injection, including potential associations with heroin use. This study aimed to identify predictors of PO injection initiation among PWUD, and examine trends in heroin use before and after initiating PO injection.. Data were merged from three cohorts of PWUD recruited between September 2005 and November 2015. Predictors of PO injection initiation were identified using extended Cox regression models. Trends in heroin use pre- and post-initiation were examined with McNemar's test and compared to matched controls with linear growth curve models.. Among 1580 participants, 247 initiated PO injection yielding an incidence density of 3.9 (95% Confidence Interval [CI]: 3.4-4.4) per 100 person-years. In a multivariable analysis, independent predictors of PO injection initiation included heroin injection (Adjusted Hazard Ratio [AHR]=4.39, 95% CI: 3.24-5.95) and non-injection PO use (AHR=1.99, 95% CI: 1.25-3.17). In a sub-analysis, compared to matched controls, PO injection corresponded with elevated heroin use post-initiation (p≤0.05).. In this study, heroin use and non-injection PO use strongly predicted PO injection initiation. Those who initiated PO injecting had elevated heroin use patterns post-initiation compared to controls. These findings suggest that transitioning to PO injection does not appear to be a substitute for heroin use among PWUD. These findings highlight the importance of addressing PO injection in harm reduction and treatment settings.

Topics: Adult; Analgesics, Opioid; Cohort Studies; Female; Follow-Up Studies; Heroin; Humans; Illicit Drugs; Injections; Male; Opioid-Related Disorders; Prescription Drug Misuse; Prospective Studies; Substance Abuse, Intravenous; Surveys and Questionnaires; Young Adult

The marked shift in the patterns of drug use in Iran, from opium smoking to injecting drug use, has led to serious health-related outcomes. This study was designed to explore characteristics of people who inject drugs (PWID) in Tehran, Iran. Nine hundred and four PWID were recruited from treatment and harm reduction facilities, as well as drug user hangouts in public areas in Tehran. Participants were interviewed using the Persian version of the World Health Organization Drug Injecting Study Phase II questionnaire. The median age at the time of the first illegal drug use, at the time of the first injection and current age was 20, 24 and 32, respectively. In more than 80% of the cases, the first drug used was opium. The transition from the first drug use to the first drug injection occurred after an average of 6.6 and 2.7 years for those who had started drug use with opium and heroin, respectively. Two-thirds of the participants shared injecting equipment within the last 6 months. Difficulty in obtaining sterile needles and thehigh cost of syringes were reported as the major reasons for needle/syringe sharing. Approximately 80% of community-recruited PWID reported difficulties in using treatment or harm reduction services. Self-detoxification and forced detoxification were the most common types of drug abuse treatment in alifetime. Despite a dramatic shift in drug policy in Iran during the past few years, wider coverage of harm reduction services, improvement of the quality of services, and education about such services are still necessary.

Topics: Adult; Drug Users; Female; Harm Reduction; Heroin; Humans; Iran; Male; Needle Sharing; Opioid-Related Disorders; Opium; Risk-Taking; Smoking; Substance Abuse, Intravenous; Surveys and Questionnaires; World Health Organization; Young Adult

The abuse of prescription opioids that are used for the treatment of chronic pain is a major public health concern, costing ∼$53.4 billion annually in lost wages, health-care costs, and criminal costs. Although opioids remain a first-line therapy for the treatment of severe chronic pain, practitioners remain cautious because of the potential for abuse and addiction. Opioids such as heroin are considered very rewarding and reinforcing, but direct and systematic comparisons of compulsive intake between commonly prescribed opioids and heroin in animal models have not yet been performed. In the present study, we evaluated the potential for compulsive-like drug seeking and taking, using intravenous self-administration of oxycodone, fentanyl, and buprenorphine in rats allowed long access sessions (12 h). We measured compulsive-like intake using an established escalation model and responding on a progressive ratio schedule of reinforcement. We compared the potential for compulsive-like self-administration of these prescription opioids and heroin, which has been previously established to induce increasing intake that models the transition to addiction in humans. We found that animals that self-administered oxycodone, fentanyl, or heroin, but not buprenorphine had similar profiles of escalation and increases in breakpoints. The use of extended access models of prescription opioid intake will help better understand the biological factors that underlie opioid dependence.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Drug-Seeking Behavior; Fentanyl; Heroin; Male; Opioid-Related Disorders; Oxycodone; Rats, Wistar; Self Administration; Time Factors

The inability to maintain drug abstinence is often referred to as relapse and consists of a process by which an abstaining individual slips back into old behavioral patterns and substance use. Animal models of relapse have been developed and validated over the last decades, and significantly contributed to shed light on the neurobiological mechanisms underlying vulnerability to relapse. The most common procedure to study drug-seeking and relapse-like behavior in animals is the "reinstatement model." Originally elaborated by Pavlov and Skinner, the concepts of reinforced operant responding and conditioned behavior were applied to addiction research not before 1971 (Stretch et al., Can J Physiol Pharmacol 49:581-589, 1971), and the first report of a reinstatement animal model as it is now used worldwide was published only 10 years later (De Wit and Stewart, Psychopharmacology 75:134-143, 1981). According to the proposed model, opioids are typically self-administered intravenously, as humans do, and although rodents are most often employed in these studies, this model has been used with a variety of species including nonhuman primates, dogs, cats, and pigeons. A variety of operant responses are available, depending on the species studied. For example, a lever press or a nose poke response typically is used for rodents, whereas a panel press response typically is used for nonhuman primates. Here, we describe a simple and easily reproducible protocol of heroin-seeking reinstatement in rats, which proved useful to study the neurobiological mechanisms underlying relapse to heroin and vulnerability factors enhancing the resumption of heroin-seeking behavior.

Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Cocaine; Conditioning, Operant; Disease Models, Animal; Heroin; Humans; Opioid-Related Disorders; Rats; Receptors, Opioid; Substance-Related Disorders

Diversion of opioid substitution drugs (OSD) is of public concern. This study examined the prevalence, frequency, and predictors of illicit OSD use in a group of injecting drug users (IDUs) and assessed if such use was associated with non-fatal overdoses.. Semi-annual cross-sectional interviews conducted in Oslo, Norway (2006-2013), from 1355 street-recruited IDUs. Hurdle, logistic, and multinomial regression models were employed.. Overall, 27% reported illicit OSD use in the past four weeks; 16.8% methadone, 12.5% buprenorphine, and 2.9% both drugs. Almost 1/10 reported at least one non-fatal overdose in the past four weeks, and roughly 1/3 reported such experience in the past year. Use of additional drugs tended to be equally, or more prevalent among illicit OSD users than other IDUs. In terms of illicit OSD use being a risk factor for non-lethal overdoses, our results showed significant associations only for infrequent buprenorphine use (using once or less than once per week). Other factors associated with non-fatal overdoses included age, education, homelessness, as well as the benzodiazepines, stimulants, and heroin use.. Users of diverted OSD may represent a high-risk population, as they used more additional drugs and used them more frequently than other IDUs. However, illicit OSD use may be less harmful than previously assumed. After accounting for an extensive set of covariates, only infrequent illicit buprenorphine use, but not methadone use, was associated with non-fatal overdoses.

Topics: Adult; Buprenorphine; Cross-Sectional Studies; Drug Overdose; Drug Users; Female; Heroin; Humans; Illicit Drugs; Male; Methadone; Middle Aged; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Risk Factors; Young Adult

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

In Indonesia, incarceration of people who inject drugs (PWID) and access to drugs in prison potentiate within-prison drug injection (WP-DI), a preventable and extremely high-risk behavior that may contribute substantially to HIV transmission in prison and communities to which prisoners are released.. This mixed method study examined the prevalence, correlates, and social context of WP-DI among HIV-infected male prisoners in Indonesia.. 102 randomly selected HIV-infected male prisoners completed semi-structured voice-recorded interviews about drug use changes after arrest, drug use cues within prison, and impact of WP-DI on HIV and addiction treatment. Logistic regression identified multivariate correlates of WP-DI and thematic analysis of interview transcripts used grounded-theory.. Over half (56%) of participants reported previous WP-DI. Of those, 93% shared injection equipment in prison, and 78.6% estimated sharing needles with ≥ 10 other prisoners. Multivariate analyses independently correlated WP-DI with being incarcerated for drug offenses (AOR = 3.29, 95%CI = 1.30-8.31, p = 0.011) and daily drug injection before arrest (AOR = 5.23, 95%CI = 1.42-19.25, p = 0.013). Drug availability and proximity to drug users while incarcerated were associated with frequent drug craving and escalating drug use risk behaviors after arrest. Energetic heroin marketing and stigmatizing attitudes toward methadone contribute to WP-DI and impede addiction and HIV treatment.. Frequent WP-DI and needle sharing among these HIV-infected Indonesian prison inmates indicate the need for structural interventions that reduce overcrowding, drug supply, and needle sharing, and improve detection and treatment of substance use disorders upon incarceration to minimize WP-DI and associated harm.

Topics: Adult; Attitude; Heroin; HIV Infections; Humans; Indonesia; Male; Methadone; Narcotics; Needle Sharing; Opioid-Related Disorders; Prevalence; Prisoners; Prisons; Risk-Taking; Substance Abuse, Intravenous

There has been a well-documented increase in the non-medical use of pharmaceutical opioids (PO) worldwide. However, there has been little detailed examination of treatment demand, or the characteristics of those presenting for treatment, particularly for treatments other than opioid substitution.. Data from closed drug and alcohol treatment episodes from the Alcohol and Other Drug Treatment Services National Minimum Data Set (AODTS-NMDS, representing non-opioid substitution treatment) in Australia for 2002-2003 to 2010-2011 were examined. In the four jurisdictions where detailed data were available, episodes where heroin was the principal drug of concern were compared to episodes for the four most frequently reported pharmaceutical opioids (morphine, codeine, fentanyl and oxycodone).. In 2002-2003, most (93%) opioid treatment was related to heroin with seven percent of all opioid treatment episodes reporting a PO as the principal drug of concern. In 2010-2011, 20% of all opioid treatment episodes were attributed to POs. Distinct changes over time were observed for different opioids. There was an increase in the average age at the start of treatment for heroin and oxycodone episodes, and a reduction in the proportion of females for codeine episodes, with 67% in 2002-2003 compared with 44% in 2010-2011. Codeine and oxycodone episodes had the lowest current or past injection rates.. Clear differences were observed over time and between different opioids. Monitoring these emerging patterns will be important to inform treatment needs, particularly in light of different patterns of poly drug use, different routes of administration and changing demographic characteristics.

Topics: Adult; Age Factors; Analgesics, Opioid; Australia; Female; Heroin; Humans; Male; Mental Health Services; Opioid-Related Disorders; Sex Factors; Young Adult

To examine the relationship between nonmedical use of prescription opioids and heroin initiation from childhood to young adulthood, and to test whether certain ages, racial/ethnic, and income groups were at higher risk for this transition.. Among a nationally representative sample of US adolescents assessed in the 2004-2011 National Surveys on Drug Use and Health cross-sectional surveys (n = 223,534 respondents aged 12-21 years), discrete-time hazard models were used to estimate the age-specific hazards of heroin initiation associated with prior history of nonmedical use of prescription opioids. Interactions were estimated between prior history of nonmedical use of prescription opioids and age of nonmedical use of prescription opioid initiation, race/ethnicity, and income.. A prior history of nonmedical use of prescription opioids was strongly associated with heroin initiation (hazard ratio 13.12, 95% CI 10.73, 16.04). Those initiating nonmedical use of prescription opioids at ages 10-12 years had the highest risk of transitioning to heroin use; the association did not vary by race/ethnicity or income group.. Prior use of nonmedical use of prescription opioids is a strong predictor of heroin use onset in adolescence and young adulthood, regardless of the user's race/ethnicity or income group. Primary prevention of nonmedical use of prescription opioids in late childhood may prevent the onset of more severe types of drug use such as heroin at later ages. Moreover, because the peak period of heroin initiation occurs at ages 17-18 years, secondary efforts to prevent heroin use may be most effective if they focus on young adolescents who already initiated nonmedical use of prescription opioids.

Topics: Adolescent; Analgesics, Opioid; Child; Cross-Sectional Studies; Drug Prescriptions; Female; Heroin; Humans; Male; Opioid-Related Disorders; Risk Assessment; Risk Factors; United States; Young Adult

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

Topics: Analgesics, Opioid; Female; Heroin; Humans; Male; Opioid-Related Disorders

A panel of nine experts applied multi-criteria decision analysis (MCDA) to determine the relative overall harm to users and harms to others of street heroin (injected and smoked) and eleven non-medically used prescription opioids. The experts assessed harm scores for each of the 13 opioids on each of 20 harm criteria, weighted the criteria and explored the resulting weighted harm scores for each opioid. Both forms of heroin scored very high: overall harm score of 99 for injected heroin and 72 for smoked heroin on a scale of 0-100. The main feature that distinguishes both forms of street heroin use is that their harm to others is more than five times that of the other eleven opioids. The overall harm score of fentanyl (including injection of fentanyl extracted from patches) and diamorphine (medically prescribed form of heroin) was 54 and 51, respectively, whereas that of orally used opioids ranged from 32 (pethidine) to 11 (codeine-containing pharmaceuticals). Injected street heroin, fentanyl and diamorphine emerged as most harmful to users, with the latter two very low in harm to others. Pethidine, methadone, morphine and oxycodone are also low in harm to others, while moderate in harm to users. We conclude that the overall harms of non-medically used prescription opioids are less than half that of injected street heroin. These data may give a basis for precautionary regulatory measures that should be considered if the rising trend in non-medical use of prescription opioids were to become evident in the UK.

Topics: Administration, Inhalation; Analgesics, Opioid; Decision Support Techniques; Decision Trees; Dosage Forms; Heroin; Humans; Injections, Intravenous; Opioid-Related Disorders; Prescription Drug Misuse; Risk Assessment; Substance Abuse, Intravenous; United Kingdom

The non-medical use of pharmaceutical opioids is associated with a range of negative health consequences, including the development of dependence, emergency room presentations and overdose deaths.. Drawing on life history data from a broader qualitative study of the non-medical use of painkillers, this brief report presents two cases of transitions from recreational or non-medical pharmaceutical opioid use to intravenous heroin use by young adults in Australia.. Although our study was not designed to assess whether recreational oxycodone use is causally linked to transitions to intravenous use, polyopioid use places individuals at high risk for progression to heroin and injecting. Our first case, Jake, used a range of analgesics before he transitioned to intravenous use, and the first drug he injected was methadone. Our second case, Emma, engaged in a broad spectrum of polydrug use, involving a range of opioid preparations, as well as benzodiazepines, cannabis and alcohol. Both cases transitioned from oral to intravenous pharmaceutical opioids use and subsequent intravenous heroin use.. These cases represent the first documented reports of transitions from the non-medical or recreational use of oxycodone to intravenous heroin use in Australia. As such, they represent an important starting point for the examination of pharmaceutical opioids as a pathway to injecting drug use among young Australians and highlight the need for further research designed to identify pharmaceutical opioids users at risk of transitions to injecting and to develop interventions designed to prevent or delay these transitions.

Topics: Administration, Intravenous; Adult; Australia; Drug Users; Female; Heroin; Humans; Male; Methadone; Opioid-Related Disorders; Oxycodone; Self Medication; Substance Abuse, Intravenous; Young Adult

Across Europe, illicit drug-related mortality has not declined despite ever increasing prevention measures. The cause of these deaths has traditionally been associated with overdose. Previous findings have revealed the appearance of non-lethal opioid concentrations, leading us to investigate a further cause of death. The symptoms of heroin intoxication with asphyxia and/or cardiovascular involvement resemble anaphylaxis, and therefore it has been speculated that such deaths might be caused by an allergic reaction. The study´s aims were to investigate levels of allergic mediators in long-term injecting drug users (IDU) compared to healthy controls and to determine if oral opioid substitution therapy (OST) resulted in similar allergic symptoms to those reported by IDU after intravenous (IV) heroin use.. We quantified the concentrations of histamine, diamine oxidase (DAO), tryptase and lipoprotein-associated phospholipase A2 (LpPLA2) at baseline and 1 h after administration of Substitol®retard (482 ± 220 mg) in 56 patients at a withdrawal centre (Austria) and compared them with healthy controls (n = 103). Questionnaires and face-to-face interviews were used to assess allergic symptoms and side effects in IDU. Descriptive statistical analyses of quantitative data were performed by using SPSS.. Baseline histamine, tryptase and LpPLA2 were significantly elevated in IDU compared to the healthy control group, while DAO decreased. Blood levels showed no significant change after oral substitution uptake. Self-reported allergic symptoms and side effects after IV heroin use were reported in 55 cases (98.2%), minimal symptoms were documented after OST (12.5%, 7/56).. This study revealed that baseline histamine concentrations were elevated in chronic IDU, although only relatively small changes in tryptase plasma levels occurred. After IV heroin application the reported allergic symptoms were mostly mild and did not lead to clinically relevant side effects. The substitution substance was clearly better tolerated than IV administered heroin. Elevated levels of allergic mediators such as histamine in IDUs may place them at greater risk of severe or fatal anaphylaxis when exposed to heroin; however, this requires further investigation.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adolescent; Adult; Amine Oxidase (Copper-Containing); Biomarkers; Case-Control Studies; Drug Hypersensitivity; Female; Heroin; Histamine; Humans; Male; Middle Aged; Morphine; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Tryptases; Young Adult

One approach to preventing opioid overdose, a leading cause of premature, preventable mortality, is to provide overdose education and naloxone distribution (OEND). Two outstanding issues for OEND implementation include 1) the dissemination of OEND training from trained to untrained community members; and 2) the concern that OEND provides active substance users with a false sense of security resulting in increased opioid use.. To compare overdose rescue behaviors between trained and untrained rescuers among people reporting naloxone rescue kit use; and determine whether heroin use changed after OEND, we conducted a retrospective cohort study among substance users in the Massachusetts OEND program from 2006 to 2010. We used chi square and t-test statistics to compare the differences in overdose management characteristics among overdoses managed by trained versus untrained participants. We employed Wilcoxon signed rank test to compare median difference among two repeated measures of substance use among participants with drug use information collected more than once.. Among 4,926 substance-using participants, 295 trained and 78 untrained participants reported one or more rescues, resulting in 599 rescue reports. We found no statistically significant differences in help-seeking (p = 0.41), rescue breathing (p = 0.54), staying with the victim (p = 0.84) or in the success of naloxone administration (p = 0.69) by trained versus untrained rescuers. We identified 325 OEND participants who had drug use information collected more than once. We found no significant overall change in the number of days using heroin in past 30 days (decreased 38%, increased 35%, did not change 27%, p = 0.52).. Among 4926 substance users who participated in OEND, 373(7.6%) reported administering naloxone during an overdose rescue. We found few differences in behavior between trained and untrained overdose rescuers. Prospective studies will be needed to determine the optimal level of training and whether naloxone rescue kits can meet an over-the-counter standard. With no clear evidence of increased heroin use, this concern should not impede expansion of OEND programs or policies that support them.

Topics: Adult; Drug Overdose; Drug Users; Female; Health Education; Health Personnel; Heroin; Humans; Male; Massachusetts; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Respiration; Retrospective Studies; Young Adult

Drug administration to avoid unpleasant drug withdrawal symptoms has been hypothesized to be a crucial factor that leads to compulsive drug-taking behavior. However, the neural relationship between the aversive motivational state produced by drug withdrawal and the development of the drug-dependent state still remains elusive. It has been observed that chronic exposure to drugs of abuse increases brain-derived neurotrophic factor (BDNF) levels in ventral tegmental area (VTA) neurons. In particular, BDNF expression is dramatically increased during drug withdrawal, which would suggest a direct connection between the aversive state of withdrawal and BDNF-induced neuronal plasticity. Using lentivirus-mediated gene transfer to locally knock down the expression of the BDNF receptor tropomyosin-receptor-kinase type B in rats and mice, we observed that chronic opiate administration activates BDNF-related neuronal plasticity in the VTA that is necessary for both the establishment of an opiate-dependent state and aversive withdrawal motivation. Our findings highlight the importance of a bivalent, plastic mechanism that drives the negative reinforcement underlying addiction.

Topics: Animals; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Gene Expression Regulation; Glutamate Decarboxylase; Heroin; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Narcotics; Opioid-Related Disorders; Rats; Rats, Wistar; Signal Transduction; Substance Withdrawal Syndrome; Ventral Tegmental Area

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

Topics: Age Factors; Data Collection; Female; Heroin; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Prescription Drugs; Risk Factors; Rural Population; Suburban Population; United States; White People

The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time.

Topics: Adult; Aged; Autopsy; Cocaine; Female; Fentanyl; Forensic Toxicology; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Substance Abuse Detection; Young Adult

Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence.. The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse).. Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine.. PROSPERO CRD42013006507.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Heroin; Humans; Methadone; Naloxone; Naltrexone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Research Design; Systematic Reviews as Topic

In the United States, overdose mortality from controlled substances has increased over the last two decades, largely involving prescription opioid analgesics. Recently, there has been speculation on a transition away from prescription opioid use toward heroin, however the impact on overdose deaths has not been evaluated.. Time series study of North Carolina residents, 2007 through 2013. Monthly ratio of prescription opioid-to-heroin overdose deaths. Non-parametric local regression models used to ascertain temporal shifts from overdoses involving prescription opioids to heroin.. There were 4332 overdose deaths involving prescription opioids, and 455 involving heroin, including 44 where both were involved (total n = 4743). A gradual 6-year shift toward increasing heroin deaths was observed. In January, 2007, for one heroin death there were 16 opioid analgesic deaths; in December, 2013 there were 3 prescription opioid deaths for each heroin death. The transition to heroin appears to have started prior to the introduction of tamper-resistant opioid analgesics. The age of death among heroin decedents shifted toward younger adults. Most heroin and opioid analgesic deaths occurred in metropolitan areas, with little change between 2007 and 2013.. The observed increases in heroin overdose deaths can no longer be considered speculation. Deaths among younger adults were noted to have increased in particular, suggesting new directions for targeting interventions. More research beyond vital statistics is needed to understand the root causes of the shift from prescription opioids to heroin.

Topics: Adult; Analgesics, Opioid; Cause of Death; Drug Overdose; Female; Heroin; Humans; Male; Middle Aged; North Carolina; Opioid-Related Disorders

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 historical patterns of opiate use show that sources and methods of access greatly influence who is at risk. Today, there is evidence that an enormous increase in the availability of prescription opiates is fuelling a rise in addiction nationally, drawing in new initiates to these drugs and changing the geography of opiate overdoses. Recent efforts at supply-based reductions in prescription opiates may reduce harm, but addicted individuals may switch to other opiates such as heroin. In this analysis, we test the hypothesis that changes in the rates of Prescription Opiate Overdoses (POD) are correlated with changes in the rate of heroin overdoses (HOD). ICD9 codes from the Nationwide Inpatient Sample and population data from the Census were used to estimate overall and demographic specific rates of POD and HOD hospital admissions between 1993 and 2009. Regression models were used to test for linear trends and lagged negative binomial regression models were used to model the interrelationship between POD and HOD hospital admissions. Findings show that whites, women, and middle-aged individuals had the largest increase in POD and HOD rates over the study period and that HOD rates have increased in since 2007. The lagged models show that increases in a hospitals POD predict an increase in the subsequent years HOD admissions by a factor of 1.26 (p<0.001) and that each increase in HOD admissions increase the subsequent years POD by a factor of 1.57 (p<0.001). Our hypothesis of fungibility between prescription opiates and heroin was supported by these analyses. These findings suggest that focusing on supply-based interventions may simply lead to a shift in use to heroin rather minimizing the reduction in harm. The alternative approach of using drug abuse prevention resources on treatment and demand-side reduction is likely to be more productive at reducing opiate abuse related harm.

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

Preclinical studies suggest that chronic drug abuse profoundly alters stress-responsive systems. The best studied of the stress-responsive systems in humans is the hypothalamic-pituitary-adrenal (HPA) axis. Apart from cortisol, arginine vasopressin peptide (AVP), and atrial natriuretic peptide (ANP) are known to directly impact upon the HPA axis in addictive behavior. We investigated alterations in ANP, AVP and cortisol serum levels in opiate-dependent patients who received diacetylmorphine treatment within a structured opiate maintenance program. ANP serum levels were significantly increased in opiate-dependent patients as compared to healthy controls, whereas AVP and cortisol serum levels were reduced. The ANP, AVP and cortisol serum levels were not significantly associated with the psychometric dimensions of heroin craving. In conclusion, chronic drug abuse profoundly alters stress-responsive systems like the HPA axis. Alterations of AVP, ANP and cortisol appear to constitute an important component in the neurobiology of opiate-dependent patients.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Enzyme-Linked Immunosorbent Assay; Fasting; Heroin; Humans; Hydrocortisone; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Psychometrics; Statistics, Nonparametric; Time Factors

Both intra-uterine exposure to maternal drugs and HIV are known to adversely affect the developing central nervous system.. (1) To describe the quality of GMs in infants who were intra-uterinely exposed to maternal opiate abuse and HIV; and (2) to analyze to what extent (a) perinatal events, (b) status of HIV-infection, and (c) the quality of GMs are associated with the neurodevelopmental outcome at 2 to 3years of age.. Seventy-seven children intra-uterinely exposed to both maternal opiate abuse and HIV in utero (41 boys and 36 girls; 39 born preterm) were videoed twice: first during the first 2months after term (writhing GMs) and again at 3-5months (fidgety GMs). Neurodevelopmental outcome was assessed at 2-3years of age.. Thirty-eight infants showed abnormal writhing GMs; 25 infants had abnormal or absent fidgety movements; 22 children had an adverse neurodevelopmental outcome. The association between GM trajectories and outcome revealed a Cramer-V=0.75 (p<0.001). Those infants with active HIV-infection (n=10) did not differ from the 67 infants who were HIV-exposed but uninfected with respect to their GM quality or outcome.. Serial assessment of GMs in infants who were intra-uterinely exposed to maternal opiates and to HIV can be utilized for early identification of infants at a higher risk for later deficits and needing early intervention.

Topics: Child Development; Developmental Disabilities; Female; Heroin; HIV Infections; Humans; Infant, Newborn; Infant, Premature; Male; Maternal-Fetal Exchange; Movement Disorders; Narcotics; Opioid-Related Disorders; Pregnancy; Pregnancy Complications, Infectious; Prenatal Exposure Delayed Effects

In order to create an effective immunization approach for a potential vaccine to heroin, liposomes containing monophosphoryl lipid A [L(MPLA)] were tested as an adjuvant system to induce antibodies to heroin hapten analogs. Four synthetic haptens and two immunization strategies were employed. In the first strategy, a hydrophobic 23 amino acid immunogenic peptide derived from the membrane proximal external region of gp41 from HIV-1 envelope protein was embedded as a carrier in the outer surface of L(MPLA), to which was conjugated a 15 amino acid universal T cell epitope and a terminal heroin hapten analog. In the second strategy, tetanus toxoid (TT) carrier protein was decorated with haptens by conjugation, and the hapten-conjugated protein was mixed with L(MPLA). After immunization of mice, each of the immunization strategies was effective for induction of IgG anti-hapten antibodies. The first immunization strategy induced a mean end-point IgG titer against one of two haptens tested of approximately 12,800; however, no detectable antibodies were induced against the liposome-associated HIV-1 carrier peptide. In the second immunization strategy, depending on the hapten used for decorating the TT, end-point IgG titers ranged from 100,000 to 6,500,000. In this strategy, in which hapten was conjugated to the TT, end-point IgG titers of 400,000 to the TT carrier were observed with each conjugate. However, upon mixing unconjugated TT with L(MPLA), anti-TT titers of 6,500,000 were observed. We conclude that L(MPLA) serves as a potent adjuvant for inducing antibodies to candidate heroin haptens. However, antibodies to the carrier peptide or protein were partly or completed inhibited by the presence of conjugated hapten.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Epitopes, T-Lymphocyte; Feasibility Studies; Female; Haptens; Heroin; HIV Envelope Protein gp41; Lipid A; Liposomes; Mice; Mice, Inbred BALB C; Opioid-Related Disorders; Peptides; Tetanus Toxoid; Vaccines

Drug addiction is a chronic brain disease that is a serious social problem and causes enormous financial burden. Because mitochondrial abnormalities have been associated with opiate addiction, we examined the effect of morphine on mtDNA levels in rat and mouse models of addiction and in cultured cells. We found that mtDNA copy number was significantly reduced in the hippocampus and peripheral blood of morphine-addicted rats and mice compared with control animals. Concordantly, decreased mtDNA copy number and elevated mtDNA damage were observed in the peripheral blood from opiate-addicted patients, indicating detrimental effects of drug abuse and stress. In cultured rat pheochromocytoma (PC12) cells and mouse neurons, morphine treatment caused many mitochondrial defects, including a reduction in mtDNA copy number that was mediated by autophagy. Knockdown of the Atg7 gene was able to counteract the loss of mtDNA copy number induced by morphine. The mitochondria-targeted antioxidant melatonin restored mtDNA content and neuronal outgrowth and prevented the increase in autophagy upon morphine treatment. In mice, coadministration of melatonin with morphine ameliorated morphine-induced behavioral sensitization, analgesic tolerance and mtDNA content reduction. During drug withdrawal in opiate-addicted patients and improvement of protracted abstinence syndrome, we observed an increase of serum melatonin level. Taken together, our study indicates that opioid addiction is associated with mtDNA copy number reduction and neurostructural remodeling. These effects appear to be mediated by autophagy and can be salvaged by melatonin.

Topics: Analgesics; Animals; Autophagy; Behavior, Animal; Cells, Cultured; Dendrites; DNA, Mitochondrial; Gene Dosage; Heroin; Hippocampus; Humans; Male; Melatonin; Mice; Mitochondria; Models, Biological; Morphine; Neurons; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome

There is a clear evidence that same psychoactive substance may cause various individual physiological reactions in same environmental conditions. Although there is a general attitude on equal liability to opioid addiction, latest genetic analysis findings imply there are certain quantifiable factors that could lead to elevated individual liability towards development of opioid addiction. The goal of this study was to investigate association of certain personality traits and genetic factors (separately and in combination) with heroin addiction. Total of 200 individuals participated in the study: 100 patients on Metadone Maintenance Treatment (MMT) and 100 age and sex matched healthy volunteers. All were medically examined, interviewed and psychologically evaluated using Eysenck personality questionnaire (EPQ) and genotyped for DRD2 (rs1800497) using PCR-RFLP method. Overrepresentation of certain personality traits (neuroticism, psychoticism and extraversion/ intraversion), together with environemental risk factors such as: upbringing within incomplete families and familial history of psychotropic substances abuse, are associated with high-risk development of opioid addiction.

Topics: Bosnia and Herzegovina; Case-Control Studies; Female; Genetic Predisposition to Disease; Genotype; Heroin; Humans; Male; Methadone; Opioid-Related Disorders; Personality; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Prospective Studies; Receptors, Dopamine D2; Risk Factors; Surveys and Questionnaires

Abuse and misuse of prescription opioids are serious public health problems. Abuse-deterrent formulations are an intervention to balance risk mitigation with appropriate patient access. This study evaluated the effects of physicochemical barriers to crushing and dissolving on safety outcomes associated with extended-release oxycodone (ERO) tablets (OxyContin) using a national surveillance system of poison centers. Other single-entity (SE) oxycodone tablets and heroin were used as comparators and to assess substitution effects.. The National Poison Data System covering all US poison centers was used to measure changes in exposures in the year before versus the 2 years after introduction of reformulated ERO (7/2009-6/2010 vs 9/2010-9/2012). Outcomes included abuse, therapeutic errors affecting patients, and accidental exposures.. After ERO reformulation, abuse exposures decreased 36% for ERO, increased 20% for other SE oxycodone, and increased 42% for heroin. Therapeutic errors affecting patients decreased 20% for ERO and increased 19% for other SE oxycodone. Accidental exposures decreased 39% for ERO, increased 21% for heroin, and remained unchanged for other SE oxycodone. During the study period, other interventions to reduce opioid abuse occurred, for example, educational and prescription monitoring programs. However, these have shown small effects and do not explain a drop for ERO exposures but not for other opioids.. After ERO reformulation, calls to poison centers involving abuse, therapeutic errors affecting patients, and accidental exposures decreased for ERO, but not for comparator opioids. Abuse-deterrent formulations of opioid analgesics can reduce abuse, but switching to other accessible non abuse-deterrent opioids might occur.

Topics: Analgesics, Opioid; Delayed-Action Preparations; Heroin; Humans; Logistic Models; Models, Structural; Opioid-Related Disorders; Oxycodone; Poison Control Centers; Prescription Drug Misuse; United States

We investigated the prevalence and correlated factors of human immunodeficiency virus (HIV) among heroin users attending methadone maintenance treatment (MMT) programs in Central Taiwan, and explored the degree of risk perception of HIV infection among the participants. Our study participants were 781 heroin users seeking treatment at the MMT program at Tsaotun Psychiatric Center in Taiwan. The presence of HIV antibodies was identified by microparticle enzyme immunoassay and confirmed by western blot. Multivariate logistic regression was used to identify the independent correlates of HIV infection. The mean age of the sample was 36.1 years [standard deviation (SD) = 7.6]; of the patients, 710 (90.9%) were men. The prevalence of HIV infection among our study population was 20.7%. Multivariate logistic regression analysis revealed that HIV infection was independently associated with the age of the patients of initial heroin use, heroin injection use, nondrug-related criminal convictions, needle-sharing behaviors, and sharing injection paraphernalia. A strong agreement existed between self-reported HIV serostatus and the results of laboratory analyses, with 88.8% of patients reporting their condition correctly. We found a high rate of HIV infection among patients in the MMT program. Factors associated with HIV infection were mostly related to drug-use behaviors. These findings stress the importance of education regarding drug-risk behaviors.

Topics: Adult; Blotting, Western; Female; Heroin; HIV Antibodies; HIV Infections; Humans; Immunoenzyme Techniques; Male; Opioid-Related Disorders; Prevalence; Taiwan

During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users.. Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status.. Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45 years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (p = 0.003). Women aged over 44 years (OR = 4.67;95 % CI = 1.29-16.96) and divorced/widowed women (OR = 14.18;95 % CI = 1.59-127.01) were more likely to be FHFs when compared to women aged less than 44 years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (n = 96; 95 %): fentanyl was detected in most (n = 91; 95 %). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (n = 37; 40.7 %). About half of these samples had detectable cocaine concentrations (n = 20; 54 %). Median fentanyl concentration in central blood samples was 0.02 μg/ml (n = 91, range <0.002-0.051 μg/ml) and 0.02 μg/ml (n = 32, range <0.004-0.069 μg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/P = 1.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77 %).. Illicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.

Topics: Adolescent; Adult; Cause of Death; Drug Contamination; Drug Overdose; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Michigan; Middle Aged; Narcotics; Opioid-Related Disorders; Prevalence; Pulmonary Edema; Sex Factors; Substance-Related Disorders; Survival Rate; Young Adult

Drug addiction is a multifactorial disorder. Researchers have posited that an individual's inherited behavioral propensity or temperament contributes to the disorder by shaping a personality strongly linked with the risk of drug abuse. Further, they hypothesize that the polymorphism of dopamine D2 receptor increases the susceptibility to and severity of addiction. We, therefore, investigated possible associations between dopamine D2 receptor (DRD2) and personality traits among intravenous heroin addicts.. We assessed 93 intravenous heroin addicts and controls using Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) and the Tridimensional Personality Questionnaire (TPQ). We confirmed drug-dependence status using a questionnaire based on DSM-IV criteria. We extracted DNA from the subjects' whole blood and genotyped it for DRD2 allelic variants.. Genotype analysis showed a significantly higher frequency for the TaqIA polymorphism among the addicts (69.9%) compared to control subjects (42.6%; Fisher's exact χ(2), p < .05). We observed no significant differences for other variants between the addicts and controls. The addicts had higher scores for novelty seeking (NS) and harm avoidance (HA) personality traits but lower scores for reward dependence (RD) when compared to control subjects.. The environmental cues are different for the addicts, and the healthy university students we used as controls. We recommend that researchers employ a gene-environment interaction approach to study factors associated with addictive behaviors in future studies.. Taq1A may be implicated for an increased vulnerability to addiction. Screening of this marker might be useful for identifying individuals at risk of addiction.

Topics: Base Sequence; DNA Primers; Heroin; Humans; Male; Opioid-Related Disorders; Personality; Polymorphism, Genetic; Receptors, Dopamine D2; Surveys and Questionnaires

Prescription opioids are the most frequently misused class of prescription drugs amongst young adults. Initiation into prescription opioid misuse is an important public health concern since opioids are increasingly associated with drug dependence and fatal overdose. Descriptive data about initiation into prescription opioid misuse amongst young injection drug users (IDUs) are scarce.. An exploratory qualitative study was undertaken to describe patterns of initiation into prescription opioid misuse amongst IDUs aged 16-25 years. Those young IDUs who had misused a prescription drug at least three times in the past three months were recruited during 2008 and 2009 in Los Angeles (n=25) and New York (n=25). Informed by an ethno-epidemiological approach, descriptive data from a semi-structured interview guide were analysed both quantitatively and qualitatively.. Initiation into prescription opioid misuse was facilitated by easy access to opioids via participant's own prescription, family, or friends, and occurred earlier than misuse of other illicit drugs, such as heroin. Nearly all transitioned into sniffing opioids, most injected opioids, and many initiated injection drug use with an opioid. Motives for transitions to sniffing and injecting opioids included obtaining a more potent high and/or substituting for heroin; access to multiple sources of opioids was common amongst those who progressed to sniffing and injecting opioids.. Prescription opioid misuse was a key feature of trajectories into injection drug use and/or heroin use amongst this sample of young IDUs. A new pattern of drug use may be emerging whereby IDUs initiate prescription opioid misuse before using heroin.

Topics: Adolescent; Adolescent Behavior; Adult; Age Factors; Analgesics, Opioid; Drug-Seeking Behavior; Family; Family Health; Female; Friends; Heroin; Humans; Los Angeles; Male; New York City; Opioid-Related Disorders; Prescription Drugs; Substance Abuse, Intravenous; Surveys and Questionnaires; Young Adult

A significant number of men with opiate misuse have sexual problems. Premature ejaculation (PE) occurs predominantly on discontinuation of the opiate but seems to persist in some cases. The aims of this study were to determine the rates of PE and other sexual dysfunctions in patients maintained on methadone; to determine the time of onset of PE in relation to onset of opiate misuse; and to look at the patients' perception of the effect of heroin and methadone on PE.. Sixty five men attending a tertiary referral clinic for methadone maintenance treatment were assessed cross-sectionally using a semi-structured questionnaire, clinical interview, review of clinical records and the International Index of Erectile Function (IIEF).. Thirty eight (58.5%) subjects reported a "lifetime" history of PE. Twenty (30.76%) of them reported "current" history of PE. Eleven (16.9%) people reported that PE preceded opiate misuse. Twenty four (63.2%) felt that heroin helped their PE and 7 (18.4%) felt that heroin worsened it. Fourteen (36.8%) felt that methadone helped PE, while 10 (26.3%) felt methadone worsened PE. Only 2 out of 65 (3.07%) reported that they had been asked about their sex life by the addiction services.. Prevalence of "current" premature ejaculation was almost 3 times greater than reported in the general population. A significant number of patients perceived heroin to be beneficial on PE. Presence of sexual dysfunction could therefore be a risk factor for relapse into heroin misuse. Most clinicians avoid asking patients questions of a sexual nature. Nevertheless, managing sexual difficulties among patients with opiate misuse could be a significant step in relapse prevention.

Topics: Adult; Cross-Sectional Studies; Ejaculation; Heroin; Humans; Interviews as Topic; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Population Surveillance; Prevalence; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Statistics, Nonparametric; Surveys and Questionnaires; United Kingdom

This study determined how the magnitude of change in positive subjective responses predicts clinical outcome in a treatment setting. Specifically, we attempted to define what constitutes a clinically important difference (CID) in subjective responses.. A 100-mm visual analog scale (VAS) measured subjective ratings of drug "high," calculated via an anchor-based method with published data from participants receiving sustained-release naltrexone (NTX) and heroin in a laboratory setting. The data were then compared to clinical outcomes in a treatment trial with sustained-release naltrexone. A distribution-based method subsequently analyzed data from participants who received ALO-01 (extended-release morphine with sequestered NTX) to predict its abuse liability.. Differences in ratings of drug high of approximately 10 mm on a 100-mm line were clinically significant. By extrapolation, CIDs were also found between crushed or intact ALO-01 and immediate-release morphine sulfate (IRMS). No CIDs were found between intact and crushed ALO-01.. From laboratory and treatment trial data involving naltrexone, calculation of CIDs in subjective ratings of high is possible. Consequently, crushing/swallowing or injecting ALO-01 produces clinically significantly less drug high than oral or intravenous morphine alone, suggesting that ALO-01 has lower abuse liability by those routes than morphine formulations.

Topics: Analgesics, Opioid; Heroin; Humans; Naltrexone; Opioid-Related Disorders

There is an established corpus of evidence linking substance abuse with neuropsychological impairment, particularly implicating frontal lobe functions. These could potentially be premorbid to, rather than consequences of, direct effects of substance abuse.. A matched pairs design was employed in which currently abstinent opiate abusers in treatment were matched to 22 healthy control individuals. These were compared for premorbid and current neurobehavioral abnormalities with the self-report Frontal Systems Behavior Scale (FrSBe). Estimated premorbid and current IQ scores were also ascertained.. There was no difference between the groups regarding socioeconomic background. There was no evidence for an alteration in cognitive function as measured by current IQ associated with opiate abuse, nor evidence of premorbidly lower IQ. However, with the FrSBe, the opiate abusers reported overall higher levels of apathy. They also had raised FrSBe total scores, indicating the presence of neurobehavioral features associated with frontal lobe impairment. Furthermore, the opiate abusers reported higher levels of these neurobehavioral abnormalities compared to their matched controls, even in the period preceding substance abuse.. The results suggest that some substance abusing individuals in treatment demonstrate raised levels of neurobehavioral abnormalities, independently of general intellectual functioning. Furthermore, the results imply that these abnormalities may have already been present prior to the effects on the nervous system of substance abuse.

Topics: Aged; Buprenorphine; Cognition; Female; Frontal Lobe; Heroin; Humans; Male; Methadone; Middle Aged; Narcotics; Neuropsychological Tests; Opiate Substitution Treatment; Opioid-Related Disorders

Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment.. We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons.. Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval [CI] 6.91-8.01) and generated a societal cost of $1.14 million (95% CI $736,800-$1.78 million). Those who received diacetylmorphine gained 7.92 discounted QALYs on average (95% CI 7.32-8.53) and generated a societal cost of $1.10 million (95% CI $724,100-$1.71 million). Cost savings in the diacetylmorphine cohort were realized primarily because of reductions in the costs related to criminal activity. Probabilistic sensitivity analysis showed that the probability of diacetylmorphine being cost-effective at a willingness-to-pay threshold of $0 per QALY gained was 76%; the probability was 95% at a threshold of $100,000 per QALY gained. Results were confirmed over a range of sensitivity analyses.. Using mathematical modelling to extrapolate results from the North American Opiate Medication Initiative, we found that diacetylmorphine may be more effective and less costly than methadone among people with chronic opioid dependence refractory to treatment.

Topics: Adult; Analgesics, Opioid; British Columbia; Chronic Disease; Cohort Studies; Cost-Benefit Analysis; Drug Costs; Female; Heroin; Humans; Male; Markov Chains; Methadone; Models, Statistical; Opiate Substitution Treatment; Opioid-Related Disorders; Quality-Adjusted Life Years

Preclinical study results suggest that neurotrophic peptides like nerve growth factor (NGF) and vascular endothelial growth factor A (VEGF-A) may be associated with symptoms of addictive behavior like withdrawal symptoms and rewarding effects. We investigated alterations in NGF and VEGF-A serum levels in opiate-dependent patients (25 male patients), who received diamorphine (DAM, heroin) treatment within a structured opiate maintenance program, and compared the results with the NGF and VEGF-A serum levels of healthy controls (23 male controls). NGF and VEGF-A serum levels were assessed before and after DAM administration twice a day (in the morning (16 h after last application--t1) and in the afternoon (7 h after last application--t3)) in order to detect a possible immediate or summative (in the afternoon) heroin effect on these two neuropeptides. Moreover, we investigated possible associations between the serum levels of these neurotrophic growth factors and psychometric dimensions of addictive behavior, e.g. craving, withdrawal, depression. Whereas there was no direct effect of DAM application on the serum levels of both neurotrophic growth factors neither in the morning nor in the afternoon, the NGF serum levels of the patient group were found to be significantly increased at all four time points of investigation compared with the healthy controls. In contrast, VEGF-A serum levels did not differ significantly in the patient and control groups. We found a significant positive association between the NGF serum levels and several items of the short opiate withdrawal scale as well as a negative association between self-reported mood (measured by visual analogue scale) and mood before heroin application (in the morning as in the afternoon). Moreover, we found a significant positive association between the NGF serum levels (t1 and t3) and the self-reported craving for methadone. In contrast, we found a negative association between the VEGF-A serum levels and avoidance, anxiety, suicide intentions of the SCL-90 as well as a positive association between the VEGF-A serum levels and the subscales of the heroin craving questionnaire measuring the rewarding effects of heroin. In conclusion, the results of this pilot study show that there might be an association between symptoms of opiate dependence and withdrawal and serum levels of VEGF-A and NGF.

Topics: Adult; Case-Control Studies; Heroin; Humans; Male; Middle Aged; Narcotics; Nerve Growth Factor; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Substance Withdrawal Syndrome; Vascular Endothelial Growth Factor A

Topics: Analgesics, Opioid; Female; Heroin; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

The leading cause of injury death among adults in Connecticut (CT), USA is drug poisonings. We analyzed the epidemiology and geographic distribution of opioid-involved accidental drug-involved intoxication deaths ("overdoses") in CT over an 11-year period.. We reviewed data from 1997 to 2007 on all adult accidental/undetermined drug intoxication deaths in CT that were referred to the Office of the Chief Medical Examiner (OCME). Regression analyses were conducted to uncover risk factors for fatal opioid-involved intoxications and to compare heroin- to prescription opioid- and methadone-involved deaths. Death locations were mapped to visualize differences in the geographic patterns of overdose by opioid type.. Of the 2900 qualifying deaths, 2231 (77%) involved opioids. Trends over time revealed increases in total opioid-related deaths although heroin-related deaths remained constant. Methadone, oxycodone and fentanyl, the most frequently cited prescription opioids, exhibited significant increases in opioid deaths. Prescription opioid-only deaths were more likely to involve other medications (e.g., benzodiazepines) and to have occurred among residents of a suburban or small town location, compared to heroin-involved or methadone-involved deaths. Heroin-only deaths tended to occur among non-Whites, were more likely to involve alcohol or cocaine and to occur in public locations and large cities.. The epidemiology of fatal opioid overdose in CT exhibits distinct longitudinal, risk factor, and geographic differences by opioid type. Each of these trends has implications for public health and prevention efforts.

Topics: Adolescent; Adult; Analgesics, Opioid; Cause of Death; Connecticut; Drug Overdose; Female; Heroin; Humans; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Prescription Drugs; Young Adult

While psychiatric comorbidity has been shown to produce a negative impact on the outcome of opioid use disorders, longitudinal studies carried out in the context of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly linked to methadone efficacy have not demonstrated a similar negative influence. To verify whether results obtained considering psychopathology in terms of formal psychiatric diagnoses were replicated when assessing psychopathology in terms of global psychiatric severity, a retrospective cohort study was designed. 259 patients commencing methadone maintenance treatment were divided into two groups on the basis of SCL-90 severity score and compared for retention in treatment, toxicological urine test results and psychological/psychiatric status throughout a one year period of observation. The results of the study suggest that patients in MMTP with high psychiatric severity are not characterized by a lower retention in treatment or higher substance use than those with low psychiatric severity. Moreover, during treatment high severe psychiatric patient status appears to improve significantly for all psychological/psychiatric dimensions explored by SCL-90. These results are consistent with those obtained in previous studies on the efficacy of MMTP, comprehensive of psychiatric care, irrespective of the severity of psychopathology exhibited by patients at the beginning of treatment.

Topics: Adult; Cocaine; Cohort Studies; Female; Heroin; Humans; Male; Mental Disorders; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Severity of Illness Index; Treatment Outcome

Topics: Analgesics, Opioid; Buprenorphine; Cocaine; Drug Overdose; Drug Prescriptions; Health Knowledge, Attitudes, Practice; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Substance-Related Disorders; United States

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

Afghanistan has become the world's largest producer of illicit opiates. Opium and its derivative heroin are widespread substances of use, abuse and dependency in Central Asia. The region is currently undergoing expanding HIV epidemics driven largely by needle sharing among people who use drugs, in contexts where public health interventions to reduce the harms associated with substance use are limited by policy, law and legalistic and repressive approaches to drug users. Evidence-based approaches to drug treatment are lacking or limited in multiple states. Urgent reform is needed. The massive volumes of Afghan's illicit opiate exports are having serious impacts on the health of the region.

Topics: Afghanistan; Asia, Central; Drug Trafficking; Drug Users; Heroin; HIV Infections; Humans; Needle Sharing; Opioid-Related Disorders; Opium; Substance Abuse, Intravenous

A harm reduction NGO in southern Yunnan operating an emergency overdose response hotline service successfully reversed 76 overdoses through the administration of naloxone in one of the first interventions of its kind in China.. To explore local understandings of risk factors related to overdose, assess ongoing barriers to overdose response, and solicit client input on how to further reduce opiate overdose mortality in Gejiu, the authors conducted qualitative interviews with 30 clients, including 15 individuals who received naloxone injections to reverse an overdose and 15 individuals who called the hotline in response to the overdose of a peer.. Participants pointed to a number of local structural shifts in heroin use including the ageing of the opiate using population and drug mixing practises that contribute to the city's overdose toll. Concerns over medical professionals' willingness to treat drug users, protection of confidentiality, and financial costs associated with treatment frequently cause drug users to avoid contact with the city's emergency service providers. Participants suggest directly distributing naloxone to clients as one strategy to further reduce overdose mortality.. The authors explore possible strategies, including targeted trainings and new partnerships with local hospitals, to further reduce opiate overdose mortality in this resource-poor setting.

Topics: Adult; Analgesics, Opioid; Attitude of Health Personnel; China; Confidentiality; Cost of Illness; Drug Overdose; Female; Harm Reduction; Heroin; Hotlines; Humans; Illicit Drugs; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Organizations; Peer Group; Pilot Projects; Risk Factors; Urban Health Services

Cognitive impairment has been reported in drug-dependent patients under opioid maintenance treatment.. To compare cognitive functioning in healthy controls and in opioid-dependent patients treated with Buprenorphine, Heroin, or methadone maintenance.. We used the standardized test battery ART-90 to study cognitive function in patients under long-term heroin treatment (n = 20), Bup (n = 22), or Met (n = 24) maintenance treatment and healthy controls (n = 25).. Patients receiving heroin performed significantly worse than healthy controls in most domains. Heroin patients performed worse than patients in the other two treatment groups in subtests measuring psychomotor performance under stress conditions and monotony.. Although a number of limitations must be taken into account, this study provides some preliminary evidence that cognitive function may be more impaired in patients under heroin maintenance treatment than in patients receiving Bup or Met and in healthy controls.

Topics: Adult; Buprenorphine; Case-Control Studies; Cognition; Female; Heroin; Humans; Male; Methadone; Middle Aged; Neuropsychological Tests; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Psychomotor Performance; Young Adult

Preclinical study results suggest that brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are involved in the modulation of addictive behaviour. We investigated alterations in serum levels of BDNF and GDNF in opiate-dependent patients (28 males) who received diacetylmorphine treatment within a structured opiate maintenance programme. BDNF (T = 2.735, p = 0.009) serum levels were significantly increased in the opiate-dependent patients as compared with healthy controls (21 males), whereas GDNF serum levels (T = 1.425, p = 0.162) did not differ significantly from GDNF serum levels of the healthy controls. BDNF serum levels were significantly associated with craving for heroin (measured by the Heroin Craving Questionnaire (r = 0.420, p = 0.029) and by the General Craving Scale (r = 0.457, p = 0.016), whereas GDNF serum levels were not associated with psychometric dimensions of heroin craving. In conclusion, our results show a positive association between BDNF serum levels and opiate craving in opiate-dependent patients.

Topics: Adult; Behavior, Addictive; Brain-Derived Neurotrophic Factor; Glial Cell Line-Derived Neurotrophic Factor; Heroin; Humans; Male; Opioid-Related Disorders

Topics: Analgesics, Opioid; Follow-Up Studies; Heroin; Humans; India; Opiate Substitution Treatment; Opioid-Related Disorders; Substance-Related Disorders

To compare pathological and toxicological features between opiate overdose and non-opiate overdose fatalities examined in the Department of Forensic Medicine, Chiang Mai University, Thailand.. A retrospective study of 142 cases, diagnosed as opiate-related deaths between 1996 and 2008 was conducted. Demographic data, pathological findings and toxicological results were retrieved from autopsy records.. Within these 142 opiate-related deaths, 102 cases were classified as opiate overdose fatalities by Forensic Medicine doctors. More than 95% ofcases were male. About 80% were aged 20 to 39 years. Forty-eight percent were Thai, 13% were British and 11% were American. The most commonplaces of death were residential areas and hotels. Pulmonary edema and needle marks were more common in opiate overdose cases than in non-opiate overdose cases. Toxicological findings showed that 61% of opiate overdose cases and 34% of non-opiate overdose cases were positive for blood morphine. Morphine was detected in about 95% of urine samples in both groups. About 62% of opiate overdose cases and 31% of non-opiate overdose cases had positive blood alcohol.. The average incidence of opiate-related death was about 1% of autopsy cases. More than two thirds of the deaths were opiate overdose cases. After the year 2003, more foreigners suffered from opiate overdose fatalities than Thais. The fatalities were confined to an area frequented by tourists. Pulmonary edema and needle puncture marks were more frequently observed in opiate overdose cases. The number of cases of morphine detection in serum from the opiate overdose group was significantly higher than in the non-opiate overdose group. There was no significant difference in urine morphine detection between both groups. Other substances detected in these victims were alcohol, benzodiazepines, methamphetamine, methylenedioxymethamphetamine and methadone. Alcohol was found significantly higher in opiate overdose fatality than in non-opiate overdose deaths.

Topics: Adult; Aged; Aged, 80 and over; Drug Overdose; Female; Heroin; Humans; Male; Middle Aged; Morphine; Opioid-Related Disorders; Pulmonary Edema; Retrospective Studies; Young Adult

Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced.

Topics: Amphetamines; Benzodiazepines; Cannabinoids; Chromatography, Liquid; Cocaine; Forensic Toxicology; Heroin; Humans; Illicit Drugs; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse Detection; Tandem Mass Spectrometry

In order to determine the comparative toxicology and systemic disease of cases of death due to methadone and heroin toxicity, 1193 coronial cases of opioid overdose that occurred in New South Wales, Australia between 1 January 1998 and 31 December 2007 were inspected. These comprised 193 cases in which cause of death involved methadone toxicity (METH) and 1000 cases in which cause of death involved heroin toxicity in the absence of methadone (HER). METH cases were significantly more likely to have benzodiazepines (63.7% vs. 32.2%), and less likely to have alcohol (23.6% vs. 42.7%) detected. METH cases were significantly more likely to be diagnosed with pre-existing systemic pathology (94.3% vs. 79.9%), and multiple organ system pathology (68.8% vs. 41.4%). Specifically, METH cases were more likely to have cardiac (58.9% vs. 34.5%), pulmonary (53.6% vs. 30.9%), hepatic (80.7% vs. 62.8%) and renal (25.0% vs. 9.5%) disease. Given the notable differences in toxicology and disease patterns, great caution appears warranted in prescribing benzodiazepines to methadone users, and regular physical examinations of methadone treatment patients would appear clinically warranted.

Topics: Adult; Analgesics, Opioid; Autopsy; Benzodiazepines; Central Nervous System Depressants; Drug Overdose; Ethanol; Female; Heroin; Humans; Kidney; Liver; Lung; Male; Methadone; Middle Aged; Myocardium; Narcotics; New South Wales; Opioid-Related Disorders

Cell therapies in animal models of neurobehavioral defects are normally derived from neural stem cells (NSC) of the developing cortex. However, the clinical feasibility of NSC therapies would be greatly improved by deriving transplanted cells and from a tissue culture source that is self-renewing, containing cells that potentially differentiate into the desired neuronal phenotypes. These cultures can be engineered to contain the appropriate factors to support their therapeutic action and likely evoke lesser immune reactions. In the current study, we employed our model of mice neurobehaviorally impaired via prenatal exposure to heroin, to test the therapeutic efficacy of NSC derived from murine embryonic stem cells culture (ESC). The culture contained elongated bipolar cells, 90% of which are positive for nestin, the intermediate filament protein found in neural precursors. After removal of growth factors, the NSC differentiated into neurons (34.0% +/- 3.8% NF-160 positive), including cholinergic cells (ChAT positive), oligodendrocytes (29.9% +/- 4.2% O(4)), and astrocytes (36.1% +/- 4.7% GFAP positive). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis confirmed the immunocytochemical findings. Mice made deficient in Morris maze behavior by prenatal heroin exposure (10 mg/kg heroin s.c. on gestational days 9-18) were transplanted into the hippocampus region on postnatal day 35 with the ES culture-derived NSC (ES-NSC) labeled with dialkylcarbocyanine (Dil) cell tracker. Dil+ and NF160+ cells were detected in the hippocampal region (50% +/- 8% survival). The transplantation completely restored maze performance to normal; e.g., on day 3, transplantation improved the behavior from the deficient level of 11.9-sec latency to the control of 5.6-sec latency (44.5% improvement).

Topics: Animals; Cell Differentiation; Cell Survival; Cognition Disorders; Disease Models, Animal; Embryonic Stem Cells; Female; Heroin; Male; Maze Learning; Mice; Narcotics; Neurogenesis; Neurons; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Stem Cell Transplantation; Stem Cells

Methadone maintenance therapy is the most widely used treatment in patients with heroin addiction. Multiple studies have suggested that both current and former heroin addicts entering a methadone maintenance treatment program have altered immune function. Our previous study indicated that heroin addicts have depressed mitogen-stimulated lymphocyte proliferation and a decrease in the modulation of lymphocyte surface markers. This immunosuppression may be mediated via the direct interaction of opiates with lymphocyte opioid receptors. In order to test this hypothesis, the levels of opioid receptors on immune cells obtained from heroin users were determined using saturation binding, and it was found that former heroin addicts on methadone maintenance treatment had a significantly reduced maximum number (B(max)) of [(3)H]naloxone binding. The B(max) values were 51.3+/-7.6 fmol/mg protein for the non-addicted group and 25.3+/-3.1 fmol/mg protein for the methadone maintenance group. Opioid receptor gene expression on the immune cell was determined using a semi-quantitative reverse-transcription polymerase chain reaction technique with specific pairs of primers to amplify mu- and delta-opioid receptor mRNAs. Both types of mRNAs were significantly decreased in lymphocytes obtained from the former heroin addicts on methadone maintenance subjects. Similarly, in an in vitro study, 100 microM methadone significantly down-regulated both mu- and delta-opioid receptor mRNA expressions in cultured lymphocytes obtained from naïve subjects. This effect was prevented by including 100 microM naloxone or pretreating with 50 ng/ml pertussis toxin. The data presented indicate that chronic opiate exposure was associated with down-regulation of G-protein-coupled opioid receptor gene expression in human lymphocytes.

Topics: Heroin; Humans; Lymphocytes; Methadone; Opioid-Related Disorders; Receptors, Opioid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To identify prognostic factors for a positive or negative termination of heroin-assisted treatment (HAT) in Switzerland.. A complete census of all 3155 patients ever admitted was analysed using the proportional hazard model (including time dependent covariates).. Median length of stay was 11.4 years; the maximal length of stay was 13.9 years. 299 positive and 463 negative terminations were registered. Terminations clustered in the first year. Both time to positive and negative termination was significantly dependent on historical treatment cohorts since 1994. Positive termination was negatively associated with treatment in larger treatment centres (OR: 0.77, CI: 0.61-0.97) and positively with income from the social system (OR: 1.33; CI: 1.03-1.72). Negative terminations were positively associated with HIV infection before treatment (OR: 1.74; CI: 1.40-2.16), delinquence (OR 1.36; CI: 1.09-1.69), and higher levels of distrust (OR: 1.18 per scoring point; CI = 1.05-1.31).. Length of stay in Swiss HAT is considerable. The proportion of positive terminations did not increase with longer stays, indicating that the majority of patients are in chronic palliative care. Negative terminations outweighed positive terminations, with a low predictive power from co-variates. The routine assessment and analysis of different covariates, such as indicators of treatment process, has the potential to improve the therapeutic outcomes of HAT.

Topics: Adult; Comorbidity; Crime; Female; Follow-Up Studies; Heroin; HIV Seropositivity; Humans; Length of Stay; Male; Models, Statistical; Narcotics; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Patient Dropouts; Prognosis; Secondary Prevention; Socioeconomic Factors; Substance Abuse Treatment Centers; Switzerland

Many methadone patients and untreated heroin users have an ambivalent attitude toward methadone maintenance. This may be a result of the widespread belief that methadone produces various side effects not found with heroin. This study compared the symptom complaints of patients on oral methadone maintenance (MMT) with those of patients prescribed injectable heroin (IHT). A convenience sample of 117 (63 MMT, 54 IHT) patients was recruited from two maintenance clinics. With the use of a self-completion questionnaire, patients were interviewed about a range of symptoms they had experienced and which, in their view, were due to maintenance substance immediately after the last 10 opioid administrations, during the previous week and previous year. The complaints of the two groups overlapped considerably with only few significant differences; these appeared related to the route of administration. IHT patients reported a larger number of complications experienced immediately after administration than MMT patients (p = .007). From the patients' view, methadone does not produce many more or side effects very different from heroin and thus seems at least as tolerable as heroin for maintenance treatment.

Topics: Administration, Oral; Adult; Female; Heroin; Humans; Injections; Male; Methadone; Narcotics; Opioid-Related Disorders; Surveys and Questionnaires

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

Iran is a significant consumer of opium, and, generally, of opioids, in the world. Addiction is one of the important issues of the 21st century and is an imperative issue in Iran. Long-term consumption of opioids affects homeostasis.. To determine the effects of opium and heroin consumption on serum biochemical parameters.. In a cross-sectional study, subjects who had consumed heroin (n = 35) or opium (n = 42) for more than two years and 35 nonaddict volunteers as the control group were compared in regard to various biochemical parameters such as fasting blood sugar (FBS), Na(+), K(+), Ca(2+), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol, creatinine, and total protein. Chromatography was used to confirm opioid consumption, and the concentration of biochemical parameters was determined by laboratory diagnostic tests on serum.. No significant differences were found in Na(+), Ca(2+), BUN, UA, TG, creatinine, and total protein concentrations among the three groups. FBS, K(+), and UA levels were significantly lower in opium addicts compared to the control group. Serum Ca(2+) concentration of heroin addicts showed a significant decrease compared to that of the control group. Both addict groups showed a significant decrease in serum cholesterol levels.. Chronic use of opium and heroin can change serum FBS, K(+), Ca(2+), UA, and cholesterol.. This study, one of few on the effects of opium on serum biochemical parameters in human subjects, has the potential to contribute to the investigation of new approaches for further basic studies.

Topics: Adult; Blood Glucose; Calcium; Case-Control Studies; Cholesterol; Cross-Sectional Studies; Heroin; Humans; Iran; Male; Opioid-Related Disorders; Opium; Potassium; Uric Acid

Buprenorphine maintenance is efficacious for treating opioid dependence, but problems with diversion and misuse of buprenorphine (BUP) may limit its acceptability and dissemination. The buprenorphine/naloxone combination tablet (BNX) was developed to reduce potential problems with diversion and abuse. This paper provides data regarding the characteristics of BUP injection drug users in Malaysia and preliminary data regarding the impact of withdrawing BUP and introducing BNX. BUP was introduced in 2002 and subsequently withdrawn from the Malaysian market in 2006. BNX was introduced in 2007.. A two wave survey of BUP IDUs was conducted shortly prior to BUP withdrawal from the Malaysian market (n=276) and six months after BNX was introduced (n=204). Six focus groups with BUP and/or BNX IDUs were also conducted shortly before the second wave.. In addition to current BUP or BNX IDU, 96% of first wave participants and 97% second wave participants reported lifetime heroin IDU preceding the onset of their BUP/BNX IDU. Additionally, 58% of first and 64% of second wave survey participants reported current heroin IDU. Benzodiazepine abuse, often injected with BUP, was reported in both the surveys. Focus group participants reported that BNX was not as desirable as BUP, nonetheless, the results of the second wave survey suggest a continuing widespread BNX IDU, at least in Kuala Lumpur.. In Malaysia, BUP and BNX IDU occur among heroin IDUs. The introduction of BNX and withdrawal of BUP may have helped to reduce, but did not eliminate the problems with diversion and abuse.

Topics: Adult; Buprenorphine; Female; Health Behavior; Health Surveys; Heroin; Humans; Injections, Intravenous; Malaysia; Male; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Opioid-Related Disorders; Patient Selection; Prevalence; Risk Management; Risk-Taking; Substance Abuse, Intravenous

Topics: Analgesics, Opioid; Australia; Contracts; Drug Prescriptions; Heroin; Humans; Legislation, Drug; Opioid-Related Disorders; Pain; Prescription Drugs

Toxic leukoencephalopathy occurs as a result of exposure to wide variety of agents. Inhalation of heroin or its vapours produces a distinct syndrome with characteristic findings on MR imaging. We report a case of heroin vapour abuse (chasing the dragon) who presented with altered sensorium. MRI of the brain showed symmetrical T2 hyperintensities over the cerebellum and hippocampi. The patient gradually improved and made good recovery but developed spasticity of all the limbs due to delayed involvement of bilateral basal ganglia. This is the first report of bilateral hippocampal involvement in a patient abusing heroin vapour.

Topics: Administration, Inhalation; Adult; Basal Ganglia; Cerebellum; Extremities; Heroin; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Muscle Spasticity; Narcotics; Opioid-Related Disorders

In diacetylmorphine prescription programs for heavily dependent addicts, diacetylmorphine is usually administered intravenously, but this may not be possible due to venosclerosis or when heroin abuse had occurred via non-intravenous routes. Since up to 25% of patients administer diacetylmorphine orally, we characterised morphine absorption after single oral doses of immediate and extended release diacetylmorphine in 8 opioid addicts. Plasma concentrations were determined by liquid chromatography-mass spectrometry. Non-compartmental methods and deconvolution were applied for data analysis. Mean (+/-S.D.) immediate and extended release doses were 719+/-297 and 956+/-404 mg, with high absolute morphine bioavailabilities of 56-61%, respectively. Immediate release diacetylmorphine caused rapid morphine absorption, peaking at 10-15 min. Morphine absorption was considerably slower and more sustained for extended release diacetylmorphine, with only approximately 30% of maximal immediate release absorption being reached after 10 min and maintained for 3-4h, with no relevant food interaction. The relative extended to immediate release bioavailability was calculated to be 86% by non-compartmental analysis and 93% by deconvolution analysis. Thus, immediate and extended release diacetylmorphine produce the intended morphine exposures. Both are suitable for substitution treatments. Similar doses can be applied if used in combination or sequentially.

Topics: Administration, Oral; Area Under Curve; Biological Availability; Chromatography, Liquid; Delayed-Action Preparations; Heroin; Humans; Mass Spectrometry; Opioid-Related Disorders; Tablets

This paper explores India's role in the world illicit opiate market, particularly its role as a producer. India, a major illicit opiate consumer, is also the sole licensed exporter of raw opium: this unique status may be enabling substantial diversion to the illicit market.. Participant observation and interviews were carried out at eight different sites. Information was also drawn from all standard secondary sources and the analysis of about 180 drug-related criminal proceedings reviewed by Indian High Courts and the Supreme Court from 1985 to 2001.. Diversion from licit opium production takes place on such a large scale that India may be the third largest illicit opium producer after Afghanistan and Burma. With the possible exceptions of 2005 and 2006, 200-300 tons of India's opium may be diverted yearly. After estimating India's opiate consumption on the basis of UN-reported prevalence estimates, we find that diversion from licit production might have satisfied a quarter to more than a third of India's illicit opiate demand to 2004.. India is not only among the world's largest consumer of illicit opiates but also one of the largest illicit opium producers. In contrast to all other illicit producers, India owes the latter distinction not to blatantly illicit cultivation but to diversion from licit cultivation. India's experience suggests the difficulty of preventing substantial leakage, even in a relatively well-governed nation.

Topics: Agriculture; Data Collection; Drug and Narcotic Control; Drug Contamination; Global Health; Heroin; Humans; India; International Cooperation; Narcotics; Opioid-Related Disorders; Opium; Surveys and Questionnaires

The object of this study is to examine the influence of maternal opiate use on the levels of second trimester biochemical markers for Down syndrome. Maternal opiate use is known to be associated with problems of placental origin and it is possible that the secretion of alpha-feto protein (AFP), free-beta human chorionic gonadotrophin (HCG) and unconjugated oestriol (UE) differs from that of a normal population.. Seventy nine women who used opiates in pregnancy were compared to a control group of seventy nine women who did not use opiates and their adjusted marker levels analysed.. The adjusted median MoM in the opiate and control groups respectively were: AFP (1.00 vs 0.94), HCG (0.95 vs 1.04) and UE (0.96 vs 1.02), with no significant difference between these groups.. This study suggests that the current practice of calculating the risk of Down syndrome from second trimester biochemistry in women using opiate can be performed using data derived from a normal population.

Topics: Adult; Biomarkers; Case-Control Studies; Down Syndrome; Female; Heroin; Humans; Methadone; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Prenatal Diagnosis; Retrospective Studies

In early 2006, government and media sources reported that crime syndicates were mixing fentanyl with heroin. This was followed by an increase in heroin overdoses and opiate-related deaths. The most recent fentanyl outbreak illustrated the need for identifying and establishing effective and responsive real-time surveillance tools to monitor drug overdoses in the United States.. In this study, poison call center data from Illinois were evaluated to determine whether the data could have detected the outbreak that occurred in Illinois in early 2006 and whether it could be used for real-time surveillance.. For this analysis, a two-step approach was used to analyze potential heroin-related calls. First, the data were analyzed retrospectively to identify whether any significant temporal shifts occurred, then a prospective analysis was conducted to simulate real-time surveillance.. Between 2002 and 2007, there were a total of 1,565 potential heroin-related calls, and the calls increased by 63.6% in 2006 compared to 2005. In the prospective analysis, the principal model would have identified the outbreak in March 2006.. If there had been a real-time surveillance program using poison center data, the outbreak would have been identified 1 month before the initial postmortem reports to the Centers for Disease Control and Prevention at the end of April 2006. Poison center data provide the potential for an earlier warning system than postmortem data sources, because the reports are usually made within hours of the exposure. Poison center data can be effectively used to monitor heroin-related exposures.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Disease Outbreaks; Drug Combinations; Drug Overdose; Female; Heroin; Humans; Illinois; Infant; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Poison Control Centers; Population Surveillance; Substance Abuse Detection; Young Adult

The 32-kDa dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein (DARPP-32) is recognized to be critical to the pathogenesis of drug addiction. Opiates via the mu-receptor act on the dopaminergic system in the brain and modulates the expression of DARPP-32 phosphoprotein which is an important mediator of the activity of the extracellular signal-regulated kinase (ERK) signaling cascades, the activation of which represents an exciting nexus for drug-induced changes in neural long-term synaptic plasticity. Silencing of DARPP-32 using an siRNA against DARPP-32 may provide a novel gene therapy strategy to overcome drug addiction. In this study, we investigated the effect of the opiate (heroin) on D1 receptor (D1R) and DARPP-32 expression and additionally, evaluated the effects of DARPP-32-siRNA gene silencing on protein phosphatase-1 (PP-1), ERK, and cAMP response element-binding (CREB) gene expression in primary normal human astrocytes (NHA) cells in vitro. Our results indicate that heroin significantly upregulated both D1R and DARPP-32 gene expression, and that DARPP-32 silencing in the NHA cells resulted in the significant modulation of the activity of downstream effector molecules such as PP-1, ERK, and CREB which are known to play an important role in opiate abuse-induced changes in long-term neural plasticity. These findings have the potential to facilitate the development of DARPP32 siRNA-based therapeutics against drug addiction.

Topics: Cells, Cultured; Dopamine and cAMP-Regulated Phosphoprotein 32; Extracellular Signal-Regulated MAP Kinases; Gene Expression; Heroin; Humans; Image Processing, Computer-Assisted; Narcotics; Oligonucleotide Array Sequence Analysis; Opioid-Related Disorders; Receptors, Dopamine D1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Transfection

Topics: Clinical Trials as Topic; Heroin; Humans; Injections, Intravenous; Methadone; Opioid-Related Disorders; United States

Topics: Cost Savings; Drug Costs; Heroin; Humans; Methadone; Opioid-Related Disorders; Patient Dropouts; Risk Assessment; Treatment Outcome

An 18-year-old woman presented with severe features of seborrhoeic dermatitis involving her scalp. Subsequently, the toe webs and intertriginous areas became affected by an erythematous, slightly scaly and weepy rash. The groin area was most severely affected, and complicated by intermittent infections with staphylococci and herpes simplex. The patient admitted to smoking heroin and was subsequently enrolled in a methadone programme. A biopsy from the groin area showed a combination of parakeratosis and keratinocyte vacuolar changes, supporting a diagnosis of necrolytic migratory erythema (NME). On completion of methadadone withdrawal, the rash cleared. The rash returned upon recommencing methadone. NME consists of an irregular annular eruption with an erythematous crusted edge. It is often mistaken for intertrigo or seborrhoeic dermatitis. In this patient, a direct effect of heroin and methadone on the epidermal metabolism might be speculated. There could be a variant of the opiate recepter, which is especially sensitive to the effects of opiates. This is the second case occurring in association with opiate dependency and the first case where the patient was rechallenged, although the precise role of the opiates in the aetiology remains somewhat speculative.

Topics: Adolescent; Analgesics, Opioid; Diagnosis, Differential; Erythema; Female; Heroin; Humans; Methadone; Necrosis; Opioid-Related Disorders; Scalp Dermatoses

Interest in oral fluid as an alternative matrix for monitoring drug use is due to its ease-of-collection and non-invasiveness; however, limited data are available on the disposition of drugs into oral fluid. The objective of this research was to provide data on the presence and concentrations of heroin, cocaine and multiple metabolites in oral fluid after illicit opioid and cocaine use. Thrice weekly oral fluid specimens (N=403) from 16 pregnant opiate-dependent women were obtained with the Salivette oral fluid collection device. Evidence of heroin (N=62) and cocaine (N=130) use was detected in oral fluid by LC-APCI-MS/MS. 6-Acetylmorphine (6-AM), heroin and morphine were the major opiates detected, with median concentrations of 5.2, 2.3, and 7.5 microg/L, respectively. Cocaine and benzoylecgonine (BE) had median concentrations of 6.4 and 3.4 microg/L. Application of the Substance Abuse Mental Health Services Administration (SAMHSA) recommended cutoffs for morphine and codeine (40 microg/L), 6-AM (4 microg/L) and cocaine and BE (8 microg/L), yielded 28 opiate- and 50 cocaine-positive specimens. Oral fluid is a promising alternative matrix to monitor opiate and cocaine use in drug testing programs. These data guide interpretation of oral fluid test results and evaluate currently proposed SAMHSA oral fluid testing cutoffs.

Topics: Analgesics, Opioid; Cocaine; Cocaine-Related Disorders; Environmental Monitoring; Female; Heroin; Humans; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Saliva

Addictive drugs have been shown to severely influence many neuronal functions, which are considered as the underlying mechanisms for physiological and psychological dependences. We previously showed that in vivo LTP in rat hippocampal CA1 region is significantly reduced during withdrawal following chronic opiates treatment, and the reduced LTP can be restored by re-exposure of animals to corresponding drugs. Here, we further demonstrated that during opiates withdrawal, the re-exposure of morphine either systemically (subcutaneously) or locally (intracerebroventricularly) could restore the reduced LTP in heroin-dependent rats, but heroin could not restore the reduced LTP, in morphine-dependent rats, indicating differential modulations of hippocampal functions by those two opiates. In contrast, DAMGO, a mu-opioid receptor (MOR) agonist, could restore the reduced LTP, and CTOP, a MOR antagonist, could block the restoration in rats dependent on both opiates, showing that MOR is functional under such conditions. However, the upregulation of hippocampal PKA activity during morphine withdrawal could be suppressed by re-exposure of morphine but not that of heroin, suggesting a likely underlying mechanism of the differential modulation of LTP by two opiates. Taken together, our study clearly demonstrates that chronic abuse of opiates inevitably leads to severe alteration of hippocampal LTP, and reveals the interesting differences between morphine and heroin in their effects on the differential modulation of hippocampal synaptic plasticity.

Topics: Animals; Behavior, Animal; Conditioning, Operant; Disease Models, Animal; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Heroin; Hippocampus; Long-Term Potentiation; Male; Morphine; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley

Topics: Analgesics, Opioid; Drug Prescriptions; Heroin; Humans; Incidence; Opioid-Related Disorders

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

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

Topics: Coroners and Medical Examiners; Forensic Pathology; Heroin; History, 20th Century; Humans; Information Systems; Methadone; Opioid-Related Disorders; Public Health; Substance Abuse Detection

Topics: Adult; Analgesics, Opioid; Australia; Buprenorphine; Codeine; Europe; Health Policy; Heroin; Humans; Methadone; Opioid-Related Disorders; Treatment Outcome; United States

To evaluate the effect of rooming-in (rather than standard nursery care) on the incidence and severity of neonatal abstinence syndrome among opioid-exposed newborns and on the proportion of mothers who retain custody of their babies at hospital discharge.. Retrospective cohort study.. Lower mainland in southwestern British Columbia.. We selected 32 women in the city of Vancouver known to have used heroin or methadone during pregnancy between October 2001 and December 2002. Comparison groups were a historical cohort of 38 women in Vancouver and a concurrent cohort of 36 women cared for in a neighbouring community hospital.. Need for treatment with morphine, number of days of treatment with morphine, and whether babies were discharged in the custody of their mothers.. Rooming-in was associated with a significant decrease in need for treatment of neonatal abstinence syndrome compared with the historical cohort (adjusted relative risk [RR] 0.40, 95% confidence interval [CI] 0.20 to 0.78) and the concurrent cohort (adjusted RR 0.39, 95% CI 0.20 to 0.75). Rooming-in was also associated with shorter newborn length of stay in hospital compared with both comparison groups. Newborns who roomed in at BC Women's Hospital were significantly more likely to be discharged in the custody of their mothers than babies in the historical cohort (RR 2.23, 95% CI 1.43 to 3.98) or the concurrent cohort (RR 1.52, 95% CI 1.15 to 2.53) were.. Rooming-in might ease opioid-exposed newborns' transition to extrauterine life and promote more effective mothering.

Topics: Adult; Breast Feeding; British Columbia; Child Custody; Cohort Studies; Comorbidity; Female; Heroin; Humans; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prevalence; Rooming-in Care; Smoking; Socioeconomic Factors; Substance-Related Disorders

Topics: Drug Combinations; Heroin; Humans; Methadone; Opioid-Related Disorders; Patient Compliance; Treatment Outcome

Opiate use in pregnancy is on the increase. There are a number of complications associated with this problem but current data from UK centres are sparse.. A retrospective study.. A North of England Hospital.. Maternal and neonatal case records were studied and a standard data set completed.. Maternal and neonatal outcomes were classified by the woman's drug usage at the end of pregnancy.. One hundred and ten babies born to 108 women were studied and 41% had evidence of previous exposure to the hepatitis C virus. Women who took heroin in later pregnancy were significantly more likely than women who were stabilised on methadone to have a baby who needed morphine (40% versus 19%), had higher mean maximum neonatal abstinence scores (NAS) (5.8 versus 4.7) and stayed in the neonatal unit significantly longer (mean 17.2 days versus 11.8 days). There were two neonatal deaths and the overall rate of prematurity was 29%.. The outcome for pregnancy in women who use opiates is complicated by high rates of prematurity and neonatal death. Women who used heroin in later pregnancy had babies who developed more severe NAS and needed a longer hospital stay than women who used only methadone.

Topics: Adult; England; Female; Heroin; Humans; Infant, Newborn; Male; Medical Records; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies

The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin (60 microg/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s.c.) showed a dose-dependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug-dependent state.

Topics: Analgesics, Opioid; Animals; Biomarkers; Body Weight; Brain; Buprenorphine; Circadian Rhythm; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Eating; Feeding Behavior; Heroin; Injections, Intravenous; Male; Motivation; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome

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: Delivery of Health Care; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Opioid-Related Disorders; United Kingdom

The relative and combined health effects of cigarette smoking, heroin use, and depression were examined in 322 clinically depressed smokers and 117 opioid-dependent smokers participating in two studies of the San Francisco Treatment Research Center. Opioid-dependent smokers averaged 16 years (S.D.=9) of heroin use; 3% of depressed smokers used opiates in the past 6 months. Cigarettes per day (M=15, S.D.=10) and Beck Depression (BDI-II) scores (M=21, S.D.=11) were comparable between the two groups. Health functioning was assessed using the Medical Outcomes Study Short Form (SF-36). Adjusting for demographic differences, depressed smokers reported better physical but poorer emotional health relative to opioid-dependent smokers. Both groups scored significantly lower than published norms (p<.05). Within groups, severity of depressive symptoms, tobacco use, and opiate use were independent predictors of lower health functioning (p<.05). Examining risk-related subgroups based on depression scores (BDI-II> or =20), cigarettes per day (> or =1 pack), and opiate use, number of risk factors was monotonically related to health functioning in both samples. Individuals with two or more risk factors scored the lowest (p<.05). Severity of depressive symptoms, tobacco use, and opiate use contributed individually and collectively to lower health functioning. Blended treatments that target multiple risk factors are needed to improve health outcomes.

Topics: Adult; Comorbidity; Depressive Disorder; Female; Health Status; Health Status Indicators; Heroin; Humans; Male; Nicotiana; Opioid-Related Disorders; Risk Factors; San Francisco; Smoking; Tobacco Use Disorder

(1) Methadone is an opiate used for replacement therapy of opiate addiction that causes dose-dependent QT prolongation. (2) Severe ventricular arrhythmias such as torsades de pointes have been reported, usually in patients on high doses (100 mg to 400 mg/day). (3) Methadone has a long plasma elimination half-life, and this poses a risk of accumulation. Accumulation is especially problematic when the dose is increased too rapidly. Combining methadone with a CYP 3A4 inhibitor increases the risk of torsades de pointes, as methadone is metabolised by this enzyme system. (4) Factors potentially predisposing patients to torsades de pointes must be analysed in each case; these include preexisting bradycardia, congenital QT prolongation, hypokalemia, and concomitant use of other drugs inducing QT prolongation. (5) This adverse effect has also been reported with levacetylmethadol (another opiate) and with heroin. It does not seem to occur with buprenorphine.

Topics: Analgesics, Opioid; Aryl Hydrocarbon Hydroxylases; Drug Interactions; Heroin; Humans; Hypokalemia; Long QT Syndrome; Methadone; Narcotics; Opioid-Related Disorders; Pain; Retrospective Studies; Risk Factors; Switzerland; Torsades de Pointes

The reported number of deaths caused by opioid use depends on the definition of an opioid-related death. In this study, we used Australian Bureau of Statistics (ABS) mortality data to illustrate how choice of classification codes used to record cause of death can impact on the statistics reported for national surveillance of opioid deaths. Using International Classification of Diseases version 10 (ICD-10) codes from ABS mortality data 1997-2002, we examined all deaths where opioids were reported as a contributing or underlying cause. For the 6-year period there was a total of 5,839 deaths where opioids were reported. Three possible surveillance definitions of accidental opioid-related deaths were examined, and compared to the total number of deaths where opioids were reported for each year. Age restrictions, often placed on surveillance definitions, were also examined. As expected, the number of deaths was higher with the more inclusive definitions. Trends in deaths were found to be similar regardless of the definition used; however, a comparison between Australian states revealed up to a twofold difference in the absolute numbers of accidental opioid-related deaths, depending on the definition. Any interpretation of reported numbers of opioid deaths should specify any restrictions placed on the data, and describe the implications of definitions used.

Topics: Accidents, Traffic; Adolescent; Adult; Australia; Cocaine; Drug Overdose; Heroin; Humans; International Classification of Diseases; Middle Aged; Opioid-Related Disorders; Population Surveillance; Public Policy; Registries; Self-Injurious Behavior

The neural mechanisms that mediate the transition from a drug-naive state to a state of drug dependence and addiction are not yet known. Here we show that a discrete population of GABA(A) receptors in the mammalian ventral tegmental area (VTA) serves as a potential addiction switching mechanism by gating reward transmission through one of two neural motivational systems: either a dopamine-independent (opiate-naive) or a dopaminergic (opiate-dependent or opiate-withdrawn) system. Bi-directional transmission of reward signals through this GABA(A) receptor substrate is dynamically controlled by the opiate state of the organism and involves a molecular alteration of the GABA(A) receptor. After opiate exposure and subsequent withdrawal, the functional conductance properties of the rat VTA GABA(A) receptor switch from an inhibitory to an excitatory signaling mode.

Topics: Animals; Bicuculline; Carbonic Anhydrases; Conditioning, Classical; Cyclic AMP Response Element-Binding Protein; Dopamine; Enzyme Inhibitors; GABA Agonists; GABA Antagonists; Heroin; Injections, Intraventricular; Male; Muscimol; Narcotics; Opioid-Related Disorders; Rats; Rats, Wistar; Receptors, GABA-A; Reward; Substance Withdrawal Syndrome; Ventral Tegmental Area

To compare the prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) carriage among injection drug users (IDUs) treated in an injection heroin maintenance program with that among IDUs treated in an oral methadone program, and to determine predictors of S. aureus carriage.. Survey.. Two opiate maintenance programs at a psychiatric university clinic.. A volunteer sample consisting of 94 (74%) of 127 IDUs treated in an injection opiate maintenance program with at least twice daily injections of heroin, and 70 (56%) of 125 IDUs treated in an oral methadone program.. Addicts treated in the intravenous heroin substitution program had a significantly lower overall rate of S. aureus carriage (37 of 94 [39.4%] vs 42 of 70 [60%]; P = .009) and a significantly lower rate of nasal carriage (21 of 94 [22.3%] vs 30 of 70 [42.9%]; P = .005) than did addicts treated in the oral methadone program. Being treated in the oral methadone program was the only independent predictor of S. aureus carriage (odds ratio, 2.27; 95% confidence interval, 1.19-4.31; P = .012). All S. aureus isolates were susceptible to oxacillin.. The regular use of needles under aseptic conditions did not increase the rate of S. aureus carriage among IDUs. Further studies are necessary to investigate whether the lower rate of S. aureus carriage among IDUs treated with intravenous heroin leads to a lower incidence of S. aureus infections in these patients.

Topics: Administration, Oral; Adult; Carrier State; Female; Heroin; Humans; Injections, Intravenous; Male; Methadone; Opioid-Related Disorders; Prevalence; Staphylococcus aureus; Substance Abuse, Intravenous; Switzerland

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

Topics: Alkaloids; Benzylisoquinolines; Biomarkers; Codeine; Gas Chromatography-Mass Spectrometry; Heroin; Humans; Opioid-Related Disorders; Opium; Predictive Value of Tests; Seeds; Substance Abuse Detection

To describe the opinions and experiences of treatment of a cohort of patients prescribed injectable opiate treatment (IOT).. Cross-sectional survey of all patients on injectable diamorphine or methadone at a tertiary referral clinic in the northwest of England in June 2000.. A total of 104 subjects were prescribed IOT, mostly male (87.5%) and with a mean age of 36.3 years (SEM 0.66, range 20-53). The majority (75.0%) were prescribed injectable methadone with the remainder (25.0%) on injectable diamorphine. Most subjects (93.3%) used intravenously, many (58.7%) into the femoral vein. Treatment was sought most frequently in order to procure a drug supply of known dose and purity, to improve family relationships and to avoid trouble with the police. Half were satisfied with their treatment but many wanted to change to injectable diamorphine or to increase their doses. Subjects cited many advantages of injectable diamorphine over injectable methadone, although benefits of injectable methadone were acknowledged.. Subjects articulated a consistent desire for IOT in order to 'stabilize' their lives in a number of ways. This sample was recruited from one of the country's largest specialist IOT clinics. The generalizability of this study's findings to all patients in the United Kingdom currently prescribed IOT, however, was not examined. Nevertheless, these findings suggest that clinicians and policy makers should be aware of many heroin users' perception of IOT as long-term treatment and their clear preference for injectable diamorphine. Further investigation of differential outcomes between oral and injectable OT and between different injectable opiates is warranted.

Topics: Adult; Cohort Studies; Cross-Sectional Studies; England; Female; Heroin; Humans; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Satisfaction; Surveys and Questionnaires

To compare the characteristics of heroin injectors vs. inhalers at their first admission to publicly funded treatment in Texas.. The sample consisted of 9732 unique clients who entered publicly funded treatment programs in Texas between 1997 and 2001 and who had a primary problem with either injected or inhaled heroin, which they had used in the past 30 days. The records were analyzed using a generalized linear model of logistic regression with the outcomes modeled as binomial and multinomial distribution and a hierarchical linear model for continuous outcomes to compare heroin inhalers and injectors.. There were large statistically significant differences between injectors and inhalers. Inhalers were more likely to be older at first use of heroin, to have entered treatment sooner, to have minor children at home, to have higher annual incomes, to be first admissions to treatment, and to have a secondary drug problem with crack cocaine. They were also more likely to be Hispanic [odds ratio (OR) = 1.74] or African-American (OR = 12.32).. Even though the race/ethnic differences in the Texas population and the type of heroin available for use in Texas differs from that studied elsewhere, many of the characteristics of heroin users are similar. Inhalers have more strengths in many areas, and these findings raise the possibility that there are factors, particularly among African-American participants in Texas, that lessen the risk of injecting heroin. Efforts should be directed to providing therapeutic interventions to discourage the transition to injecting and to encourage inhalers to enter treatment earlier rather than progressing on to injecting. This analysis is the first part of a larger study of heroin users in public and private treatment.

Topics: Administration, Inhalation; Adult; Database Management Systems; Female; Heroin; Hospital Records; Humans; Logistic Models; Male; Opioid-Related Disorders; Patient Admission; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Texas

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

Topics: Alkaloids; Benzylisoquinolines; Biomarkers; Codeine; Gas Chromatography-Mass Spectrometry; Heroin; Humans; Opioid-Related Disorders; Opium; Predictive Value of Tests; Seeds; Substance Abuse Detection

Since January 1994, heroin-assisted treatment for opiate addicts has been available in Switzerland. This is the first report of the long-term effects of this form of treatment. The report examines subjects who entered a study involving medical prescription of opiates (Projekt zur ärztlichen Verschreibung von Betäubungsmitteln; PROVE) in Switzerland between January 1994 and March 1995 (n = 366). Opiates were dispensed in eight treatment centres. A follow-up was conducted 6 years after treatment entry. Two groups were assessed: clients who have continuously been on heroin-assisted treatment since entry into the PROVE study or who re-entered this treatment, and ex-clients who had discontinued heroin-assisted treatment at the time of follow-up. Two kinds of comparisons were conducted. Firstly, conditions at treatment entry were compared to 6-year follow-up outcomes, and secondly, outcomes were compared between clients still on heroin-assisted treatment and those who had been discharged. It was found that 46% of the clients still alive were on heroin-assisted treatment at the time of follow-up. A comparison of the present living conditions showed very little difference between those in treatment and those who had terminated treatment. Compared to the situation at entry, the results of the follow-up showed a significant decrease in the use of illegal substances, illegal income and most other variables concerning social conditions, but they also showed an increase in unemployment and reliance on social benefits. Heroin-assisted treatment is thus efficacious in the long-term course of treatment and is still effective after termination of treatment with respect to living conditions and use of illicit substances.

Topics: Activities of Daily Living; Adult; Clinical Trials as Topic; Female; Follow-Up Studies; Heroin; Humans; Life Style; Long-Term Care; Male; Narcotics; Opioid-Related Disorders; Patient Dropouts; Risk-Taking; Social Adjustment; Substance Abuse Detection; Switzerland; Treatment Outcome

At a follow-up clinic for infants of opiate-dependent mothers it was noted that more infants than expected developed strabismus. This study aimed to assess the prevalence of strabismus and the need for active strabismus surveillance in this population.. Consecutive infants of opiate-dependent mothers born over an 18 mo period were recalled for ophthalmological assessment by an ophthalmologist and orthoptist. Those unable to attend were surveyed by telephone using a questionnaire.. 49 (69%) of the 71 eligible infants were recalled at a mean age of 21 mo (range 6-39); 29 had a full ophthalmological examination and the remaining 20 completed the questionnaire only. Seven (14%) of the 49 recalled infants had strabismus on examination; 4 needed glasses or patching. A further seven (14%) had a history of intermittent strabismus but declined formal examination. Another child had significant hypermetropia without strabismus. The mean age at which strabismus was observed was 8.3 mo (range birth to 19 mo). The presence of strabismus was not significantly influenced by conditions at birth, maternal drug doses, family history or need for or duration of abstinence treatment.. The rate of strabismus in infants of opiate-dependent mothers was at least 10 times that in the general population. As attendance at follow-up is often poor, paediatricians should be aware of the association to encourage opportunistic assessment and ophthalmological surveillance of this population.

Topics: Australia; Codeine; Cross-Sectional Studies; Female; Heroin; Humans; Infant; Infant, Newborn; Male; Maternal-Fetal Exchange; Methadone; Morphine; Narcotics; Neonatal Abstinence Syndrome; Neonatal Screening; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; Severity of Illness Index; Strabismus

Despite the widespread avoidance of detoxification in the second or third trimesters, there is no clear evidence to support the view that methadone withdrawal is harmful in pregnant opiate dependent women. We investigated the safety of methadone detoxification in pregnancy in a retrospective case series of 101 pregnant opiate dependent women who underwent a 21-day in-patient methadone withdrawal. One miscarriage occurred in the first trimester (n = 5; incidence rate ratio of 6.87 compared to population norms (95% CI = 0.16-47.3; p =.15)). No miscarriages were observed in the second trimester (n = 54; incidence rate ratio = 0 compared to population norms (95% CI = 0-3.69; p =.27). One premature delivery occurred in the third trimester (1 in 158 weeks at risk compared to 1 in 150 weeks in population norms; p =.16). Methadone detoxification treatment was not associated with any increased risk of miscarriage in the second trimester or premature delivery in the third trimester.

Topics: Abortion, Spontaneous; Adult; Female; Heroin; Humans; Methadone; Obstetric Labor, Premature; Opioid-Related Disorders; Pregnancy; Pregnancy Trimesters; Retrospective Studies; Substance Withdrawal Syndrome

To investigate the receptor binding affinity and naloxone-precipitated cAMP overshoot of dihydroetorphine, fentanyl, heroin, and pethidine in Sf9 insect cells expressing human mu-opioid receptor (Sf9-mu cells).. Competitive binding assay of [3H]ohmefentanyl was used to reveal the affinity for mu-opioid receptor in Sf9-mu cells. [3H]cAMP RIA was used to determine cAMP level. Antinociceptive activity was evaluated using degree 55 mouse hot plate test. Naloxone-precipitated withdrawal jumping was used to reflect physical dependence in mice.. All drugs displayed antinociceptive activity and produced physical dependence in mice. The K(i) values of dihydroetorphine, fentanyl, heroin, and pethidine in competitive binding assay were (0.85+/-0.20) nmol, (59.1+/-11.7) nmol, (0.36+/-0.13) micromol, and (12.2+/-3.8) micromol respectively. The binding affinities of these drugs for mu-opioid receptor in Sf9-mu cells were paralleled to their antinociceptive activities in mice. After chronic pretreatment with these drugs, naloxone induced cAMP withdrawal overshoot in Sf9-mu cells. The dependence index in Sf9-mu cells was calculated as K(i) value in competitive binding assay over EC(50) value in naloxone-precipitated cAMP assay. The physical dependence index in mice was calculated as antinociceptive ED(50)/withdrawal jumping cumulative ED(50). There was a good linear correlation between dependence index in Sf9-mu cells and physical dependence index in mice.. The Sf9-mu cells could be used as a cell model to evaluate the receptor binding affinity and physical dependent liability of analgesic agents.

Topics: Analgesics, Opioid; Animals; Baculoviridae; Binding, Competitive; Cells, Cultured; Cyclic AMP; Etorphine; Female; Fentanyl; Heroin; Male; Mice; Opioid-Related Disorders; Receptors, Opioid, mu; Spodoptera; Transfection

The Fas receptor is involved in the regulation of apoptosis but also can function as a non-apoptotic signal transducer. This study was mainly designed to quantitate Fas proteins in rat brain during heroin addiction and opiate withdrawal. In rat, mouse and human brains, and in SH-SY5Y cells, similar forms of Fas were immunodetected with different antibodies (i.e., 35 kDa native Fas and 48- and 51-kDa glycosylated Fas). Acute (2 h) treatments with the micro-opioid receptor agonists heroin (10 mg/kg) and morphine (30 mg/kg) increased the immunodensity of native Fas (124% and 36%) but not that of glycosylated Fas in the cerebral cortex. Chronic (5 days) heroin (5-30 mg/kg) and morphine (10-100 mg/kg) were also associated with increased native Fas (76% and 45%) and with different expressions of glycosylated Fas. In heroin-dependent rats, opiate withdrawal (48 h) resulted in a sustained increase in native Fas (107%) and in up-regulation of 51 kDa glycosylated Fas (51%). Acute treatments with selective delta-receptor (SNC-80, 10 mg/kg) or kappa-receptor (U 50488-H, 10 mg/kg) agonists did not alter the content of native or glycosylated Fas. Chronic pentazocine (10-80 mg/kg, 5 days), a mixed opiate drug and sigma(1) receptor agonist, decreased native (48%) and glycosylated (38-82%) Fas proteins. Similarly, the selective sigma(1) agonist (+)-SKF 10047 also decreased native Fas (37%) and the effect was blocked by the sigma(1) antagonist BD 1063. Brain dynamin was up-regulated by acute and/or chronic heroin (30-39%), morphine (47-85%), pentazocine (51%) and heroin withdrawal (74%). The main results indicate that chronic heroin/morphine treatment and heroin withdrawal are associated with up-regulation of 35 kDa native Fas (and with different expressions of glycosylated Fas), and also with concomitant increases of dynamin in rat brain.

Topics: Animals; Blotting, Western; Cell Line; Cerebral Cortex; Dynamins; fas Receptor; Heroin; In Vitro Techniques; Morphine; Opioid-Related Disorders; Pentazocine; Rats; Rats, Sprague-Dawley; Receptors, sigma; Substance Withdrawal Syndrome

Topics: Buprenorphine; Diagnostic Errors; Gas Chromatography-Mass Spectrometry; Heroin; Humans; Immunoassay; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Abuse Detection

Topics: Drug Prescriptions; Europe; Health Care Rationing; Health Policy; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Opioid-Related Disorders; Program Evaluation; Randomized Controlled Trials as Topic; Rehabilitation; Substance Abuse, Intravenous

To determine the scale and practice of diamorphine (heroin) prescribing for opiate dependence in the United Kingdom in 2000.. Postal survey.. England, Scotland and Wales.. One hundred and eleven of the 164 doctors in the United Kingdom on the Home Office record as holding a licence to prescribe diamorphine (response rate 68%), and 59 of the 108 doctors in the United Kingdom eligible to hold a licence (working in drug clinics), but not doing so (response rate 54%).. The characteristics of doctors (a) holding a licence and (b) currently prescribing; the number of opiate users receiving a prescription; current treatment delivery, clinical criteria for patient eligibility; and reasons for prescribing or not prescribing diamorphine.. Seventy of the 111 doctors actually held a licence. While the majority were consultant psychiatrists, five were general practitioners. Forty-six were currently prescribing to 448 patients. The majority of prescribers reported that they had not initiated a prescription for diamorphine but had inherited patients already receiving such a prescription. Most of those who prescribed considered that in selected cases it could produce clinical and social improvement. There were great variations in clinical criteria for patient eligibility, prescribing practice, daily dose prescribed (range 5-1500 mg) and the daily dose-equivalent of 100 mg methadone (range 50-900 mg). Many respondents cited lack of appropriate resources as a reason for not prescribing to more patients. Reasons for non-prescribing varied from lack of resources to little evidence of its effectiveness.. The prescribing of diamorphine to opiate dependent drug users remains rare in the United Kingdom. Not all eligible doctors seek a licence to prescribe, and not all those with licences actually prescribe it. There is no clear consensus on who should be treated with diamorphine and in what way.

Topics: Health Surveys; Heroin; Humans; Narcotics; Opioid-Related Disorders; Practice Patterns, Physicians'; United Kingdom

A growing literature suggests that excessive temporal discounting of delayed rewards may be a contributing factor in the etiology of substance abuse problems. Little is known, however, about how drug deprivation may affect temporal discounting of delayed rewards by drug-dependent individuals.. To examine the extent to which opioid deprivation affects how opioid-dependent individuals discount small, medium and large quantities of delayed heroin and money.. Thirteen opioid-dependent individuals maintained on buprenorphine completed a hypothetical choice task in which they choose between a constant delayed reward amount and an immediate reward amount that was adjusted until they expressed indifference between both outcomes. The task was completed for three values of heroin and money rewards during eight sessions under conditions of opioid deprivation (four sessions) and satiation (four sessions).. Across conditions, hyperbolic functions provided a good fit for the discounting data. Degree of discounting was significantly higher when subjects were opioid deprived. Consistent with previous findings, degree of discounting was higher for heroin than money and inversely related to the magnitude of the reward.. Opioid deprivation increased the degree to which dependent individuals discounted delayed heroin and money. Understanding the conditions that affect how drug-dependent individuals discount delayed rewards might help us understand the myopic choices made by such individuals and help improve treatment outcomes.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Female; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Outpatients; Reinforcement Schedule; Reward

Methadone maintenance treatments (MMTs) are the commonest substitution treatments offered to opiate addiction in Switzerland, in order to reduce criminal behaviour, infectious disease transmission and overdose death.. To investigate the relationship between the increase in the number of methadone maintenance treatments, criminal activity of addicts and overdose-related deaths, an ecological study was undertaken in the Canton of Geneva, from 1983 to 1999.. The regular and extensive increase in the number of MMTs is not significantly associated, during the 1983-1999 period, with a fall either in drug addict incarcerations or in overdose-related deaths. However, a slight decrease is observed in the number of imprisoned opiate addicts since 1994, and a marked decrease is seen in overdose deaths from 1997 on. An important and stable number of these deaths is due to methadone itself.. Public health objectives to diminish delinquency and overdose deaths cannot solely be fulfilled by extensive use of MMTs. A positive result could appear when access to MMT is highly favoured. This hypothesis must be proved correct by observational studies conducted on a general population.

Topics: Crime; Drug Overdose; Heroin; Humans; Methadone; Opioid-Related Disorders; Prevalence; Switzerland

Topics: Europe; Heroin; Humans; Opioid-Related Disorders

Opiate use in vivo and in vitro reduces the ability of human peripheral lymphocytes to repair DNA damage caused by both the physical and chemical mutagens that produce single-strand adducts. This decrease in repair leads to increased genetic damage to the individual cell as measured by cytogenetic damage, including sister chromatid exchanges and formation of micronuclei. The expected consequences of this increase in damage can also be established by increases in host cell mutation rate and rate of apoptosis. The effect of this increase in genetic damage can be expected to have significant consequences for HIV-1 or simian immunodeficiency virus infecting those lymphocytes. For example, DNA damaging agents have long been known to induce lentiviral growth and propagation, and this has been found to be true for HIV-1 following ultraviolet light treatment of lymphocytes. However, to date, no one has fully explored the consequences of increased host mutation rate on HIV growth and maintenance. Recent reports have demonstrated the role of viral mutation in such key physiologic processes as resistance to highly active antiretroviral therapy (HAART). Beyond the effects of random mutations in the viral genome, specific mutations in the HIV-1 transcriptase and protease lead to increased accumulation of mutant viruses and the gradual failure of HAART. It therefore remains to be tested whether changes in host cell mutation rate will also predict changes in susceptibility to drug therapy. This also leads to questions about whether the higher rate of viral mutation in HIV-infected drug addicts might be the basis for higher rates of neuroAIDS in this population. It would be attractive to speculate that the increase in the heterogeneity of the virus in addicts produces mutants with a greater capacity to attack neuronal tissue and a high affinity to replicate there.

Topics: Cocaine; DNA Repair; Heroin; HIV Infections; HIV-1; Humans; Lymphocytes; Morphine; Mutation; Narcotics; Opioid-Related Disorders; Ultraviolet Rays

This study was undertaken to determine (1) the methadone serum trough level adequate to prevent withdrawal symptoms in heroin-addicted pregnant women and (2) whether the methadone serum trough level in symptomatic women with withdrawal symptoms differs from that of asymptomatic women.. Pregnant women addicted to heroin were followed up prospectively between March 1, 1999, and March 1, 2000, in a specialized multidisciplinary methadone program after in-hospital stabilization. After counseling, women signing Institutional Review Board-approved informed consent had their methadone serum trough (20-24 hours after last dose) level checked at regular intervals throughout pregnancy. Methadone levels were kept blinded from clinicians. Methadone doses were increased only according to withdrawal symptoms. Methadone levels of asymptomatic (without withdrawal symptoms) women were compared with methadone serum trough levels of symptomatic (with withdrawal symptoms) women.. Mean methadone serum trough level was 0.295 +/- 0.16 mg/L in asymptomatic women (n = 44) and 0.175 +/- 0.11 mg/L in symptomatic (n = 58) women (P <.001). The mean methadone dose in asymptomatic patients was 101 +/- 42 mg versus 114 +/- 43 mg in symptomatic patients (P =.1). No patient had a toxic-range methadone trough level (all <0.7 mg/L). By receiver operating characteristic curve, the best differentiating methadone trough level between asymptomatic and symptomatic women was 0.24 mg/L. These differences in methadone serum trough levels between asymptomatic and symptomatic women were not influenced by continuing drug abuse, maternal weight, or gestational age when methadone serum trough level was drawn.. Mean methadone serum trough level in asymptomatic pregnant women is approximately 0.3 mg/L, and levels of 0.24 mg/L or greater should be considered adequate to prevent withdrawal symptoms in pregnancy. Knowledge of these levels will help management of the frequently noncompliant heroin-addicted pregnant woman. Appropriate daily dosing to achieve these levels is usually between 50 and 150 mg methadone, with the occasional need for even higher doses in the third trimester.

Topics: Female; Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prospective Studies; ROC Curve

To determine whether maternal methadone dosage affects duration and degree of neonatal narcotic withdrawal.. This was a retrospective cohort study of pregnant women with opioid addiction who delivered live-born singletons between April 1990 and April 2001. Inpatient detoxification or outpatient methadone maintenance therapy was offered. Women who had a positive drug screen or whose neonate tested positive for opioids were considered to be supplementing. We evaluated indices of neonatal withdrawal according to the maximum daily methadone dosage in the last week of pregnancy.. Seventy women with opioid addiction were followed. Median methadone dosage was 20 mg (range 0-150 mg), and 32 infants (46%) were treated for narcotic withdrawal. Among women who received less than 20 mg per day, 20-39 mg per day, and at least 40 mg per day of methadone, treatment for withdrawal occurred in 12%, 44%, and 90% of infants, respectively (P < 0.02). Methadone dosage was also correlated with both duration of neonatal hospitalization and neonatal abstinence score (r(s) =.70 and.73 respectively, both P <.001). Neonates were more likely to experience withdrawal if their mothers were supplementing with heroin, 68% versus 35% (P =.01). Regardless of supplementation, there was a significant relationship between methadone dosage and neonatal withdrawal (P <.05).. Maternal methadone dosage was associated with duration of neonatal hospitalization, neonatal abstinence score, and treatment for withdrawal. Heroin supplementation did not alter this dose-response relationship. In selected pregnancies, lowering the maternal methadone dosage was associated with both decreased incidence and severity of neonatal withdrawal.

Topics: Adult; Analysis of Variance; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gestational Age; Heroin; Humans; Infant, Newborn; Maternal-Fetal Exchange; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Probability; Retrospective Studies; Risk Assessment; Substance Withdrawal Syndrome; Time Factors

Topics: Heroin; Humans; Injections, Intravenous; Narcotics; Opioid-Related Disorders; Substance Abuse Treatment Centers; Switzerland; Treatment Outcome

The law enforcement and treatment policies of the Nixon administration are often credited with ending the epidemic of heroin addiction that rose in America's cities in the 1960s. In this article it is argued that although the interventions did in fact cause a major change in heroin distribution and use, the epidemic did not end in any simple way. The decline in heroin and increase in methadone that resulted from the Nixon policies lead to a shift for many addicts in both clinical and street settings from one narcotic to another. The temporary shortage of heroin that resulted from law enforcement was quickly compensated for with methadone, as well as with new distribution systems from Southeast Asia and Mexico. In the end, the interventions caused a change in an enduring "heroin system," a change that left that system in a stronger form in terms of supply and in a situation of continuing growth in terms of the number of addicts.

Topics: Drug and Narcotic Control; Heroin; Heroin Dependence; History, 20th Century; Humans; Methadone; Narcotics; Opioid-Related Disorders; United States

Self-report validity of recent drug use among heroin abusers depends on many factors including the population being studied and the setting in which the study is carried out. This study was conducted by the treating physicians to assess the self-report validity of recent heroin use by heroin dependent patients in the outdoor setting using 'thin layer chromatography' (TLC) and two highly sensitive methods of urinalysis viz. 'gas liquid chromatography' (GLC) and 'high performance liquid chromatography' (HPLC). Out of seventy-six heroin dependent patients who entered the study, 64 provided urine sample on the same day. Patients' self-report about recent opiate use was found to have a moderate agreement with urinalysis report. However, it is important to validate it with urinalysis during the treatment process because a substantial proportion of patients fails to report recent opiate use. It is recommended that all drug dependence treatment centres should be equipped with a sensitive urinalysis facility. Otherwise, the outcome of the treatment process should be considered with caution.

Topics: Adult; Analgesics, Opioid; Chromatography, Gas; Chromatography, High Pressure Liquid; Female; Heroin; Humans; India; Interviews as Topic; Male; Middle Aged; Opioid-Related Disorders; Patient Compliance; Reproducibility of Results; Substance Abuse Treatment Centers

Chronic exposure to opiates eventually leads to drug addiction, which is believed to involve maladaptive changes in brain function, but the underlying neuronal mechanisms remain primarily unknown. Given the known effects of opiates such as morphine and heroin on hippocampal function, we investigated the potential effect of chronic opiate treatment on long-term potentiation (LTP) at CA1 synapses in rat hippocampus, a leading experimental model for studying synaptic plasticity. Our results revealed that chronic exposure of rats to morphine or heroin, which induced severe drug tolerance and dependence, markedly reduced the capacity of hippocampal CA1 LTP during the period of drug withdrawal (from approximately 190% in control to approximately 120%). More interestingly, the capacity of LTP could be restored to the normal level by re-exposure of the animals to opiates, indicating that the synaptic function was already adapted to opiates. Morris water maze test, which measures behavioral consequences of synaptic plasticity, showed parallel learning deficits after chronic exposure to opiates. Moreover, the opiate-reduced LTP could also be restored by inhibitors of cAMP-dependent protein kinase A (PKA), suggesting that upregulation of cAMP pathway was likely one of the underlying mechanisms of the observed phenomena. These findings demonstrated that chronic opiate treatment can significantly modulate synaptic plasticity in the hippocampus, leading to an opiate dependence of the plasticity.

Topics: Animals; Behavior, Animal; Cyclic AMP-Dependent Protein Kinases; Drug Administration Schedule; Electric Stimulation; Electrodes, Implanted; Enzyme Inhibitors; Excitatory Postsynaptic Potentials; GABA Antagonists; Heroin; Hippocampus; In Vitro Techniques; Injections, Subcutaneous; Long-Term Potentiation; Male; Maze Learning; Morphine; Narcotics; Neuronal Plasticity; Opioid-Related Disorders; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Substance-Related Disorders; Synapses

The efficacy of methadone for treating heroin dependence derives, in part, from suppression of opiate withdrawal and attenuation of the effects of heroin.. The purpose of this double-blind, within-subject, inpatient study was to determine whether larger doses of methadone, which are more effective in the treatment of opioid dependence, produce greater or longer-lasting blockade of the effects of heroin in addition to adequate withdrawal suppression.. Participants were maintained on 30, 60, and 120 mg methadone (ascending order) for approximately 3 weeks at each dose. During each maintenance period, heroin challenges were administered at 4, 28, and 52 h after the last methadone dose. Opioid agonist effects and opioid withdrawal symptoms were assessed prior to heroin challenge. Challenge sessions consisted of three doses of heroin (0, 10, and 20 mg/70 kg; ascending order) 45 min apart.. All three methadone maintenance doses produced similar agonist effects. Participants tested 4 h after receiving 120 mg methadone showed complete suppression of withdrawal symptoms and full attenuation of the effects of heroin. Thirty and 60 mg methadone suppressed withdrawal for up to 52 h, but failed to block completely the effects of heroin. The effects of heroin increased slightly at longer post-methadone intervals.. Heroin use may persist during methadone treatment because low to moderate doses of methadone suppress withdrawal, but fail to eliminate the effects of heroin. These results provide a mechanism for the clinical observation that higher methadone doses are more effective at reducing heroin use.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Dose-Response Relationship, Drug; Double-Blind Method; Heroin; Humans; Male; Methadone; Opioid-Related Disorders; Substance Withdrawal Syndrome

Switzerland introduced heroin-assisted treatment as a routine treatment for drug addicts. As a result the evaluation instruments were changed from a detailed scientific project to a routine monitoring system. The process for developing this monitoring system is described.. The questionnaires and assessment instruments were restyled with staff of the treatment agencies. Indicators measuring quality of treatment and measures from the future national statistic on the addiction support system were integrated into admission, course and discharge questionnaires. Currently a system for feedback to treatment agencies is being developed.. All 21 treatment agencies are participating in the monitoring. Assessment quality is high.. The described monitoring should provide continuous delivery of basic relevant data on patients.

Topics: Adult; Evidence-Based Medicine; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Substance Abuse Detection; Switzerland

Criticism of methadone treatment abounds in all countries where this intervention is available. Although such criticism is often justified, it is critical to recognize that methadone is the most effective, safe, and cost-effective intervention available, is supported by innumerable studies, and provides considerable benefit to drug users, their families and communities. The major causes of the pervasive deficiencies of methadone treatment is the severe and consistent under-funding and hostile environment, both inevitable by-products of the global commitment over recent decades to an expensive, ineffective, and often counter-productive drug policy overly reliant on supply reduction. Methadone treatment is often criticized by drug war supporters not because of its limitations, but because its very effectiveness highlights the meagre benefits of supply reduction. The compelling arguments to expand pharmacotherapies for heroin dependence by rigorously evaluating prescription heroin treatment should not be based on the real or perceived deficiencies of methadone treatment. Rather, these arguments should be based on the need to provide evidence-based treatment for drug users which has the capacity, range of options, and quality expected in other health care services. The paramount aim should be to improve the current deplorable rates of death, disease, crime, and severe distress now evident in an increasing number of countries.

Topics: Attitude; Canada; Heroin; Humans; Methadone; Opioid-Related Disorders; Substance Abuse, Intravenous

Although methadone treatment has been available in North America for decades, only a small proportion of opiate addicts (some 25% of estimated opiate users in Canada) are receiving methadone treatment. Many users have tried methadone treatment, often multiple times, but leave treatment prematurely. Others would not consider it as a worthwhile treatment option for themselves. This exploratory study examines regular opiate users' attitudes towards and experiences with methadone treatment in Canada, primarily setting out to determine what makes methadone an unsuccessful or even an undesirable treatment option for considerably large groups of opiate users. This empirical effort to explore the limitations of existing methadone treatment comes at an appropriate time, when alternative forms of opiate pharmacotherapy treatment are being proposed in Canada as complementary modes of intervention that hope to address the shortcomings of methadone treatment. The rationale for this study were feasibility questions and development efforts for a clinical trial in North America evaluating the effectiveness of using injectable opioids (heroin, dilaudid) in attracting and engaging treatment-resistant opiate users into treatment. Data for this exploratory qualitative study was collected in 1999 through a series of focus groups involving 47 treatment-experienced and treatment-naive opiate users in Vancouver, Montreal, and Toronto, with the objective of identifying key themes and issues on the described topic as a basis for further systematic research.

Topics: Adult; Attitude; Focus Groups; Heroin; Humans; Methadone; Middle Aged; North America; Opioid-Related Disorders; Substance Abuse, Intravenous

The present paper describes the type and prevalence of co-morbid psychiatric disorders in a group of opioid dependent addicts.. In 17 Swiss centres for heroin-assisted treatment 85 opiate addicts were assessed at entry using the SKID interview.. Lifetime prevalence of co-morbid Axis I or Axis II disorders was 86 %. Most frequently patients were diagnosed with a personality disorder (58 %). Second frequently were mood disorders with a prevalence of 55 %, followed by anxiety disorders with a prevalence of 26 %.. The high prevalence of co-morbid psychiatric disorders indicate the urgent necessity to further develop and adapt health services for opioid addicts.

Topics: Adult; Alcoholism; Cocaine-Related Disorders; Comorbidity; Cross-Sectional Studies; Diagnosis, Dual (Psychiatry); Female; Heroin; Heroin Dependence; Humans; Male; Mental Disorders; Opioid-Related Disorders; Psychiatric Status Rating Scales; Rehabilitation Centers; Substance-Related Disorders; Switzerland

This paper reviews the current practice of injectable opiate treatment (IOT) in the United Kingdom, i.e. the "British system" of prescribing injectable heroin and methadone, and considers some of the clinical and ethical issues it raises. There is very limited research evidence supporting either the safety or effectiveness of IOT as practised in Britain. In particular there is almost no evaluation of long-term outcomes of IOT, which is of potential concern given the possibility of some patients remaining indefinitely in IOT, the risk of vascular complications, and its higher cost compared with oral maintenance. It would be easy to assess this controversial intervention as in need of further research. However, striving towards best practice in IOT involves more than generating evidence. The likelihood of a patient receiving IOT in the United Kingdom appears to be influenced more by the personal inclinations of prescribers than by outcome data (if any), or identified community needs for access to IOT. The author asks is this good clinical practice and is it sustainable? The "British system" needs to modernise itself consistent with international paradigms of continuous quality improvement, and the NHS's own agenda of clinical governance.

Topics: Analgesics, Opioid; Ethics, Medical; Heroin; Humans; Injections; Methadone; Opioid-Related Disorders; Professional Practice; United Kingdom

Asian countries adjacent to the Golden Triangle and their neighbors have witnessed an evolution in "drug abuse" from traditional opium smoking to heroin eating, smoking, and finally heroin injection. A recent study of 630 heroin users was conducted in China's Yunnan Province, located close to the Golden Triangle. Data collected between August 1997 and February 1998 indicate injecting heroin users, in comparison to noninjectors, were more likely to have used drugs for a longer period of time, and to use drugs more frequently everyday. Other major differences existed between urban and rural subjects, especially highlighting differences between men and women. Women comprised a much higher proportion of urban subjects than rural subjects. Rural injectors were much more likely to be male, but urban injectors were almost evenly split between men and women. The emerging epidemic of heroin use in China and the continuing substance abuse problem in the United States provide an opportunity for collaborative research of mutual benefit.

Topics: Acquired Immunodeficiency Syndrome; Adult; Catchment Area, Health; China; Demography; Female; Heroin; HIV Seropositivity; Humans; Incidence; India; Male; Opioid-Related Disorders; Opium; Recurrence; Thailand

Topics: Adult; Chronic Disease; Cost-Benefit Analysis; Crime; Female; Follow-Up Studies; Government Programs; Heroin; Humans; Male; Narcotics; Opioid-Related Disorders; Program Evaluation; Prospective Studies; Rehabilitation; Socioeconomic Factors; Switzerland

Traditional indications for the prescription of opioids to addicts are continuous opioid abuse despite qualified addiction treatment or temporary substitution treatment, if temporarily detoxification is not possible due to external circumstances. These criteria are demonstrated by an historical example, the treatment of the opioid addicted Swiss author Friedrich Glauser (1896-1938). From a modern public health perspective, however, opioid abuse is mainly conceptualised as risk behaviour with aversive consequences for the individual abuser and the public. These consequences should be reduced by prescription of hygienically safe heroin. In this concept, the failure of former addiction treatment is not a necessary condition for heroin prescription. Difficulties in reaching an agreement about indications for heroin prescription are partially results of inherent contradictions between an individual centered traditional medical concept and a public health concept about the goals of opioid addiction treatment.

Topics: Adult; Drug Prescriptions; Heroin; History, 20th Century; Humans; Male; Narcotics; Opioid-Related Disorders; Switzerland

Topics: Heroin; Humans; Injections, Intravenous; Opioid-Related Disorders; Substance Abuse Treatment Centers; Switzerland; Treatment Outcome

Heroin-assisted substitution treatment for severely opioid-dependent drug users has been available in Switzerland since 1994. Our aim was to ascertain the feasibility, safety, and efficacy of this treatment.. We did a cohort study in 21 community outpatient treatment centres. We assessed 1969 opioid-dependent drug users, who began heroin-assisted substitution treatment between January, 1994, and December, 2000, to ascertain admission and discharge patterns, and patient characteristics. We also followed up a subset of 237 patients who began treatment between Jan 1, 1994, and March 31, 1995, and who stayed with the programme for at least 18 months. We used questionnaires, interviews, and medical examinations done at entry and after 6, 12, and 18 months to assess somatic and mental health, social integration, and treatment outcomes.. More than 70% (1378) of patients remained in treatment for more than a year. Treatment showed positive effects with respect to health and social outcomes. A long stay in treatment was related to a higher chance of starting abstinence-oriented therapy than a short stay.. Heroin-assisted substitution treatment might be an effective option for chronically addicted patients for whom other treatments have failed.

Topics: Adult; Counseling; Feasibility Studies; Female; Heroin; Humans; Injections, Intravenous; Length of Stay; Male; Narcotics; Opioid-Related Disorders; Substance Abuse Treatment Centers; Switzerland; Treatment Outcome

In a series of licit and illicit drug-related deaths, qualitative and quantitative analyses on extracts of adipose tissue and skin were performed by GC/MS. In all cases, the adipose tissue was found to contain drugs at concentrations lower than, approximately equal to, or even greater than the concentrations of the same analytes found in the blood, which may reflect a consequence of long-term chronic exposure, or acute intoxication, or some combination of both. Approximately one cubic inch of skin with adipose tissue was removed from the mid to lower abdominal region adjacent to the midline incision during autopsy. The drugs were recovered from the specimens following incubation and alkaline, acidic, and alkaline chloroform back extraction of one to three grams of tissue. Deuterated analogs of the analytes were added to the matrix at the beginning of the incubation period. Cocaine and free morphine (from heroin) were readily identified in several cases. The presence of these illicit drugs in adipose tissue raises significant forensic questions, especially the use of 'sweat patches' to monitor recent cocaine or heroin use in chronic drug users.

Topics: Adipose Tissue; Cocaine; Cocaine-Related Disorders; Deuterium; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Morphine; Narcotics; Opioid-Related Disorders; Radiopharmaceuticals; Skin; Substance Abuse Detection; Sweat

Opiate reinforcement has been hypothesized to be mediated by an inhibition of mesolimbic gamma-aminobutyric acid (GABA) release that subsequently disinhibits ventral tegmental area (VTA) dopamine neurons. In support of this hypothesis, this study demonstrates that when administered directly into the lateral ventricle, the VTA, or the ventral pallidum, but not the nucleus accumbens, gamma-vinyl-GABA (GVG, an irreversible GABA-transaminase inhibitor, 20-50 microg) dose dependently blocked heroin (0.06 mg/kg) self-administration (SA), as assessed by an increase in heroin SA at low doses of GVG and an initial increase followed 1 to 2 h later by a blockade of heroin SA at higher GVG doses. This effect lasted 3 to 5 days. In drug-naïve rats, intra-VTA GVG pretreatment also prevented or delayed acquisition of heroin SA for 2 days. This GVG effect was prevented or reversed by systemic or intra-VTA pretreatment with the GABA(B) antagonist 2-hydroxysaclofen, but not the GABA(A) antagonist bicuculline. Similarly, coadministration of heroin with aminooxy-acetic acid (1-4 mg/kg) or ethanolamine-O-sulfate (50-100 mg/kg), two reversible GABA transaminase inhibitors, dose dependently reduced heroin reinforcement. Coadministration of (+/-)-nipecotic acid (0.1-5 mg/kg) with heroin, or intra-VTA or -ventral pallidum pretreatment with (+/-)-nipecotic acid (10 microg) or NO-711 (2 microg), two GABA uptake inhibitors, significantly increased heroin SA behavior, an effect also blocked by systemic 2-hydroxysaclofen, but not bicuculline. Taken together, these experiments, for the first time, demonstrate that pharmacological elevation of mesolimbic GABA concentration blocks heroin reinforcement by activating GABA(B) receptors, supporting the GABAergic hypothesis of opiate reinforcement and the incorporation of GABA agents in opiate abuse treatment.

Topics: 4-Aminobutyrate Transaminase; Animals; Baclofen; Behavior, Animal; Bicuculline; Enzyme Inhibitors; GABA Antagonists; GABA-A Receptor Antagonists; GABA-B Receptor Antagonists; gamma-Aminobutyric Acid; Globus Pallidus; Heroin; Injections, Intraventricular; Lateral Ventricles; Male; Microinjections; Narcotics; Neurotransmitter Uptake Inhibitors; Nucleus Accumbens; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Self Administration; Telencephalon; Ventral Tegmental Area; Vigabatrin

The purpose of this study was to investigate fatal poisonings among drug addicts in 1997 and to compare the results to similar investigations from 1985 and 1991.. All fatal intoxications among drug addicts in Denmark in 1997, investigated at the three Institutes of Forensic Medicine in Denmark.. The number of fatal intoxications increased by 32% from 1991 to 1997, mainly outside the metropolitan area, The average age increased from 32 to 36 years. The proportion of heroin/morphine intoxications increased from 57% to 71%. The most commonly used drugs were as in 1991 heroin/morphine, diazepam and methadone. The frequency of cocaine increased from one positive case in 1991 to 14% positive cases in 1997.. This study showed an increasing number of fatal intoxications and changes in drug abuse pattern and place of death since 1991.

Topics: Adolescent; Adult; Analgesics, Opioid; Cause of Death; Denmark; Drug Overdose; Female; Forensic Medicine; Heroin; Humans; Male; Methadone; Middle Aged; Morphine; Opioid-Related Disorders; Substance-Related Disorders

A total of 95 Caucasian opioid-dependent patients were followed over a one-year period in an outpatient methadone treatment program. The frequency of the TaqI A(1) allele of the D(2) dopamine receptor (DRD2) gene was 19.0% in these patients compared with 4.6% in controls free of past and current alcohol and other drug abuse and free of family history of alcohol and other drug abuse (p = 0.009). Twenty-two of these patients dropped out of the methadone program (Group A), 54 had a successful treatment (Group B), and 19 had a poor treatment (Group C) outcome. The frequency of the A(1) allele was highest in Group C (42.1%), followed by Group A (22.7%) and was lowest in Group B (9.3%). The more than fourfold higher frequency of the A(1) allele in the poor treatment outcome group compared with the successful treatment outcome group was significant (p = 0.00002). Moreover, the average use of heroin (grams/day) during the year prior to study entry was more than twice as great in patients with the A(1)(+) allele (A(1)/A(1) or A(1)/A(2) genotype) than those with the A(1)(-) allele (A(2)/A(2) genotype) (A(1)(+) allele = 0.55 +/- 0. 10, A(1)(-) allele = 0.25 +/- 0.05; p = 0.003). The results indicate that DRD2 variants are predictors of heroin use and subsequent methadone treatment outcome and suggest a pharmacogenetic approach to the treatment of opioid dependence.

Topics: Adult; Alleles; Analgesics, Opioid; Analysis of Variance; DNA; Female; Follow-Up Studies; Gene Frequency; Genotype; Heroin; Humans; Male; Methadone; Opioid-Related Disorders; Receptors, Dopamine D2

The pharmacokinetics and pharmacodynamics of high-dose intravenous (i.v.), oral and rectal diacetylmorphine (diamorphine, heroin, DAM) preparations were compared.. Two heroin-dependent patients participating in a heroin-assisted treatment program received single or repeated doses of 200 - 690 mg DAM i.v., orally (capsules, controlled-release tablets) and rectally. Plasma and urine profiles of DAM and metabolites were monitored by high-performance liquid chromatography and gas chromatography mass spectrometry, flash and high effects by visual analog scaling (VAS).. DAM was only detectable in plasma after i.v. administration. With a t 1/2 beta of 1.3 - 2.2 min it was rapidly desacetylated to 6-acetylmorphine which was further metabolized to morphine and its 3- and 6-O-glucuronide. Morphine-3-glucuronide was the dominating metabolite in plasma and urine independent of the administration route. Oral and rectal doses and dosage intervals were adequate to produce flash and high effects without any cardiovascular and respiratory side-effects nor withdrawal symptoms.. Oral and rectal DAM should further be tested and validated on a wider patient group for the non-invasive, long-term application of high-dose DAM within heroin-assisted treatment programs as alternative to the harmful i.v. application.

Topics: Administration, Oral; Adult; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Opioid-Related Disorders; Pilot Projects; Suppositories

To examine trends in treated opiate misuse and identify factors associated with route of heroin use.. Cross-sectional survey.. Services providing addiction treatment in Dublin.. Individuals making their first ever contact seeking treatment for current opiate misuse, between January 1991 and December 1996.. Data on socio-demographics and current drug use.. The study population was 3981. Over the 6-year period, there was a 330% increase in the number of new attenders. The proportion of females increased. The mean age of first opiate use declined and users began presenting earlier in their opiate-using careers, causing a decline in the age profile of new attenders. Heroin users were more likely to smoke (chase) rather than inject after 1994 (odds ratio 3.3, 95% confidence interval 2.4-4.5). Apart from year of presentation, the other significant independent predictors of chasing as the preferred route of heroin use were being in employment, shorter history of use, less frequent use, younger age, longer period in education and absence of polydrug use. Gender did not independently predict route of use.. Ireland has joined the growing number of European countries witnessing a movement towards heroin chasing. This has coincided with a surge in the number of people entering treatment. We are concerned that the greater acceptability of this route of use may be drawing increased numbers of individuals into heroin use.

Topics: Adult; Age Distribution; Cross-Sectional Studies; Drug Administration Routes; Female; Heroin; Humans; Ireland; Male; Opioid-Related Disorders; Sex Distribution; Substance Abuse, Intravenous

Reported are the results of a survey to assess the prevalence of illicit drug use among high-school students in Jamaica. A total of 2417 high-school students in 26 schools were covered: 1063 boys and 1354 girls of whom 1317 were grade-10 students (mean age 15.7 years) and 1100 were grade-11 students (mean age 16.8 years). Of the students, 1072 and 1345 were from rural and urban schools, respectively, while 1126 and 1291 were children of parents who were professionals and nonprofessionals, respectively. The following drugs were used by the students: marijuana (10.2%), cocaine (2.2%), heroin (1.5%) and opium (1.2%). Illicit drug use among males, urban students and children of professionals was higher than that among females, rural students and children of nonprofessionals, respectively.

Topics: Adolescent; Cocaine-Related Disorders; Female; Heroin; Humans; Jamaica; Male; Marijuana Abuse; Narcotics; Opioid-Related Disorders; Opium; Prevalence

The aim of the study was to determine indications and contraindications for prescription of neuroleptics in opium addiction and to study their influence on the state of the patients at different stages of the treatment. 197 patients were treated: 185 men aged 15-62 years and 12 women aged 16-35 years. The duration of the addiction was from 6 months to 18 years. It was found that therapy with neuroleptics is a necessary component of a combined treatment in the acute phase of the withdrawal syndrome and at the first stages of the following therapy. At the late stages the necessity of their administration decreased. An administration of sulpiride, alimemazine, periciazine, and thioridazine was more preferable; withdrawal psychoses were relieved with droperidol and haloperidol most effectively. In a period of antirelapse maintenance therapy administration of sulpiride, periciazine and thioridazine is indicated. Application of the preparations of prolonged action in contraindicated because of the possibility of neurolepsy development. It is emphasized that neuroleptics fail to stop a drive to narcotics and are not suitable to correct sleep.

Topics: Adolescent; Adult; Antipsychotic Agents; Chronic Disease; Contraindications; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Recurrence; Substance Withdrawal Syndrome

A 17-year-old girl was found dead in a public toilet with fresh needle puncture marks. She was 18-20 weeks pregnant with a male fetus. Drug screening of her blood and urine indicated recent heroin use. Chronic drug use was confirmed by hair analysis. Amniotic fluid as well as fetal and maternal tissues and body fluids were analyzed by GC/MS and HPLC. All the fetal specimens were investigated, and the following levels of drugs were found: 6-monoacetyl-morphine (blood: 152 ng/g; amniotic fluid: 128 ng/g; brain: 140 ng/g; lung: 110 ng/g; liver: 2 ng/g; kidney: 40 ng/g), morphine (blood: 1360 ng/g; amniotic fluid: 604 ng/g; brain: 710 ng/g; lung: 1030 ng/g; liver: 2060 ng/g; kidney: 1100 ng/g), codeine (blood: 70 ng/g; brain: 60 ng/g; lung: 60 ng/g; liver: 90 ng/g; kidney: 70 ng/g), and morphine-3-glucuronide (amniotic fluid: 209 ng/g; brain: 170 ng/g; lung: 325 ng/g; kidney: 231 ng/g). Morphine-6-glucuronide was present in the maternal circulation but could not be detected in the fetal circulation.

Topics: Adolescent; Amniotic Fluid; Autopsy; Body Fluids; Codeine; Fatal Outcome; Female; Fetus; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Humans; Male; Maternal-Fetal Exchange; Morphine Derivatives; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Tissue Distribution

In this study a rat self-administration model was used to examine the effects of training dose and time in the session on the dose-effect curve for heroin. Doses of heroin lower than 5.4 microg/inf maintained higher rates of drug intake in animals trained with 5.4 microg/inf compared to 18 microg/inf. Doses greater than 5.4 microg/inf maintained similar rates of intake in both groups of animals. The dose-response curve was shifted downward and to the right as the session progressed for animals trained with 5.4 microg/inf of heroin; however, the shift in the dose-intake curve over the session was less pronounced when the training dose was 18 microg/inf. Naltrexone and naltrindole were administered to animals in which responding was engendered with infusions of 5.4 microg of heroin to determine the effects of these antagonists in the context of time is the session. The potency of naltrexone decreased across the 4 h of the session with a time course that was consistent with literature reports on the elimination kinetics of naltrexone in rat brain. In contrast, there was not a significant interaction between naltrindole dose and session time. Therefore, the rates of heroin intake in rats are dependent not only upon the dose available for self-administration, but upon the session time and training dose as well.

Topics: Animals; Dose-Response Relationship, Drug; Heroin; Male; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Rats; Rats, Inbred F344; Self Administration; Time Factors

Topics: Acute Disease; Administration, Inhalation; Fatal Outcome; Heroin; Humans; Male; Middle Aged; Opioid-Related Disorders; Pancreatitis

NEUROFILAMENT (NF) proteins, the major components of the neuronal cytoskeleton, have been shown to represent previously unknown targets for the chronic effects of morphine in rats. This study was designed to evaluate the abundance of immunoreactive NF-L (68 kDa) proteins in post-mortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. Levels of NF-L proteins were assessed by immunoblotting techniques. Levels of immunoreactive NF-L proteins were markedly decreased (47%, n = 17) in the frontal cortex. The reduced abundance of brain NF-L proteins was not related to the post-mortem delay or to the plasma concentrations of opiates, suggesting that the observed changes represent a specific long-term effect of opiate drugs. Because of the functions associated with NF proteins (e.g. axonal transport), this finding suggests that opiate drugs may induce neuronal damage after chronic abuse in humans.

Topics: Adult; Blotting, Western; Cerebral Cortex; Drug Overdose; Female; Heroin; Humans; Male; Methadone; Molecular Weight; Neurofilament Proteins; Opioid-Related Disorders

Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance abuse. Substance abuse is associated with novelty seeking, a heritable human personality trait which may be influenced by alleles of the dopamine D4 (DRD4) gene exon III VNTR. Consequently Kotler et al analysed the DRD4 VNTR in opiate-dependent subjects from Israel, and found a significant excess of the 7-repeat allele. We have attempted to replicate this finding using a Han Chinese case-control sample of 121 heroin-dependent subjects and 154 normal controls. We found two 7-repeat alleles which occurred exclusively in the patient group, and overall there was an excess of longer alleles, which did not reach significance (chi 2 = 7.04; P = 0.07). When the D4 VNTR was divided into 'long' (5-7 repeats) and 'short' (2-4 repeats), a significant excess of long alleles was observed in the patient group (P = 0.023, one-tailed), with an odds ratio of 2.30 (95% CI 1.07-4.93). We conclude that our findings support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for heroin abuse.

Topics: Adolescent; Adult; Aged; Asian People; Exons; Female; Genetic Linkage; Genotype; Heroin; Humans; Male; Middle Aged; Minisatellite Repeats; Opioid-Related Disorders; Receptors, Dopamine D2; Receptors, Dopamine D4

Topics: Acetylation; Heroin; Humans; Morphine; Opioid-Related Disorders

The measures taken by the National Government in 1991 against drug problems in Switzerland included new therapeutic experimentation; among others, it mentioned trials with diversified prescription of narcotics (including injectable heroin, morphine and methadone as well as smokable heroin and cocaine) to heroin-dependent persons with severe health and/or social problems. The number of persons receiving heroin is limited to 250, for a period not exceeding the end of 1996. The trials have to respond to scientific criteria of evaluation as well as to standards of comprehensive care. Research questions concern the feasibility, the efficacy and the cost effectiveness of trials in comparison with usual methadone maintenance programs. First trials started in Zurich, others are planned in Basle, Berne, Fribourg, Olten, Schaffhausen, Thun and Zug.

Topics: Clinical Trials as Topic; Cocaine; Drug Prescriptions; Female; Heroin; Humans; Male; Methadone; Morphine; Narcotics; Opioid-Related Disorders; Pilot Projects; Program Evaluation; Research Design

A study of 50 opiate addicts attending a London service for treatment of drug dependence found that 47 subjects had previously made at least one attempt at self-detoxification. These subjects reported 212 previous attempts. Although 30 subjects reported having managed to complete at least one attempt, the success rate per episode was low (24%). One of the most commonly reported methods, used by 28 subjects, involved an abrupt cessation of opiates ('cold turkey'). Of the drugs used in their attempts at self-detoxification, benzodiazepines were reported by 24 subjects and opiates by 20. Practical strategies such as distraction and avoidance were also used. Self-help detoxification materials for opiate addicts might be useful.

Topics: Adult; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Opioid-Related Disorders; Remission, Spontaneous; Self Care; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Topics: Heroin; Heroin Dependence; Hospitalization; Humans; Methadone; Neurologic Examination; Opioid-Related Disorders; Substance Withdrawal Syndrome

This study compares the withdrawal responses of methadone and heroin addicts during a ten-day in-patient detoxification programme with methadone. Contrary to suggestions in the literature, the methadone group reported more severe withdrawal symptoms during both the acute withdrawal phase and the recovery phase. There were no differences between the two groups in onset or duration of symptoms. Whereas there may be reasons to favour methadone as a maintenance drug, its use may lead to difficulties during withdrawal.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Substance Withdrawal Syndrome

One hundred and four drug addicts admitted to hospital during the period 1982-1986 were studied in order to evaluate whether detoxification from opiates in a protected environment had positive long-term results, namely a definitive rejection of the world of drugs. A follow-up of this population was carried out at the start of the current year and approximately 20% were found to be drug-free. Accumulated experience leads to the conclusion that hospitalisation may have a positive long-term outcome if a subject with proven motivation to "give up" is carefully selected, and if the subject is then inserted in a broader social health project.

Topics: Follow-Up Studies; Heroin; Heroin Dependence; Hospitalization; Humans; Italy; Longitudinal Studies; Methadone; Motivation; Opioid-Related Disorders; Therapeutic Community

The role of drug availability and psychological proneness in opioid addiction was examined using longitudinal data from the Drug Abuse Reporting Program (DARP). The sample included 424 addicts who were followed up and interviewed approximately 12 years after admission to treatment in the DARP, and for whom admission, during-treatment, and 6-year follow-up data were also available. Drug availability and proneness were both found to be important for drug use at any given time--from initial stages of addiction as well as in Year 12 of the follow-up--but proneness was rated as relatively more important for opioid use in the later stages of the addiction career. Proneness measures contributed more to the prediction of long-term drug use outcomes.

Topics: Adult; Ambulatory Care; Female; Follow-Up Studies; Heroin; Heroin Dependence; Hospitalization; Humans; Illicit Drugs; Male; Methadone; Narcotics; Opioid-Related Disorders; Social Environment; Therapeutic Community

A single intracerebral injection of oxytocin activated the behavior, increased the frequency and amount of hippocampal theta-rhythm whereas vasopressin elicited opposite effects during "open field" test in drug-dependent rats with implanted electrodes in different brain structures.

Topics: Animals; Behavior, Animal; Electroencephalography; Heroin; Hippocampus; Male; Opioid-Related Disorders; Oxytocin; Rats; Rats, Inbred Strains; Vasopressins

Topics: Alcoholism; Anxiety; Clonidine; Dextropropoxyphene; Heroin; Humans; Inactivation, Metabolic; Kinetics; Methadone; Mood Disorders; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Topics: Chromatography, Thin Layer; Codeine; Gas Chromatography-Mass Spectrometry; Heroin; Humans; Morphine; Narcotics; Opioid-Related Disorders

Topics: China; England; Heroin; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; Humans; India; Morphine; Opioid-Related Disorders; Opium; United States

This study examines the relationship between self-reported use of opiates and the dose of oral methadone found to be needed on admission to an in-patients drug dependence unit. The sample consisted of all opiate addicts admitted in a 12-month period. For methadone addicts there was a close relationship between the two dose measures: for heroin addicts there was no relationship. Users of illicit heroin who generally state doses in 'grammes', reported a mean daily dose of 312.5 mg, but needed only 43 mg of oral methadone. Mean values for methadone addicts were 56 mg self-reported use, and 49 mg needed on the drug unit. Some of the reasons for the discrepancy in the two doses for the heroin addicts are discussed and clinical implications with regard to prescribing for opiate addicts are drawn.

Topics: Adult; Female; Heroin; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders

Topics: Family; Female; Heroin; History, 20th Century; Humans; Opioid-Related Disorders; Politics; Prisons; Religion; Substance-Related Disorders; Therapeutic Community

The effects of ascending and descending doses of buprenorphine (0.014-0.789 mg/kg/day) and methadone (0.179-11.86 mg/kg/day) on opiate and food intake were studied in Macaque monkeys over 195 to 245 days. Food (1-g banana pellets) and i.v. drug self-administration (heroin 0.01 or 0.02 mg/kg/injection or Dilaudid 0.02 mg/kg/injection) were maintained on a second-order schedule of reinforcement [FR 4 (VR 16:S)]. Buprenorphine (0.282-0.789 mg/kg/day) produced a significant suppression of opiate self-administration at 2.5 to 7 times the dose shown to be effective in human opiate abusers (P less than .05-.001). Methadone (1.43-11.86 mg/kg/day) did not suppress opiate self-administration in four of five monkeys across a dose range equivalent to 100 to 800 mg/day in man. The distribution of opiate self-administration across drug sessions did not account for the absence of methadone suppression as monkeys took 43% of the total daily opiate injections during the first daily drug session, 2.5 hr after methadone administration. During buprenorphine maintenance, food intake remained stable or increased significantly above base-line levels. Methadone maintenance was associated with significant decrements in food intake in four of five monkeys. Buprenorphine appeared to be significantly more effective in suppressing opiate self-administration than methadone across the dose range studied. Buprenorphine had none of the toxic side effects (seizures, respiratory depression, profound psychomotor retardation) associated with high doses of methadone over 6 to 8 months of daily drug treatment. These data are consistent with clinical studies of buprenorphine effects on heroin self-administration in human opiate addicts.

Topics: Animals; Buprenorphine; Depression, Chemical; Disease Models, Animal; Feeding Behavior; Heroin; Humans; Hydromorphone; Macaca mulatta; Macaca nemestrina; Methadone; Morphinans; Opioid-Related Disorders; Self Administration

Within our study population of 100 women for whom 3,980 urine toxicology reports were accomplished, 98 percent were multi-drug users. This proportion is far greater than would have been calculated from the percent of urines that were positive for the drugs of abuse and is a more realistic estimate of the extent of the problem than is often reported. Despite this high percentage of multi-drug use, due to the uniqueness of our patient population (pregnant women), it is not possible to deny them pharmacologic therapy for their addiction. Therefore, the use of urine toxicology reports in our clinical setting has broader implications than adherence to the methadone regulations. These reports serve as excellent devices to assess newborn abstinence symptomatology, in addition to helping us monitor the physical and psychological status of our patients. The implications are that self-medication may be used to achieve a particular effect concomitant with methadone therapy. The effects are generally to enhance the action of methadone and to decrease undesirable side effects.

Topics: Amphetamine; Diazepam; Female; Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders; Pregnancy; Substance-Related Disorders

Topics: Female; Fetal Alcohol Spectrum Disorders; Fetal Diseases; Heroin; Humans; Methadone; Opioid-Related Disorders; Pregnancy; Substance-Related Disorders

Analgesic ED50 values were determined for s.c. morphine, etorphine, heroin and methadone in mice implanted for 3 days with etorphine pellets. Tolerance to morphine (9-fold) was greater than to the other agents (2- to 4-fold). These results agreed with the previously reported unidirectional non-cross-tolerance effect seen after morphine pellet implantation where tolerance to the hydrophilic agent (morphine) was greater than for the more lipophilic agents (etorphine and heroin). As greater tolerance was found to s.c. morphine than for i.c.v. morphine, this manifestation of tolerance was described as a dispositional tolerance. Experimentally, we were able to observe two additional manifestations of tolerance. After pellet removal, the ED50 values for s.c. morphine, heroin and methadone initially increased before returning to control values. Similarly, both morphine and etorphine ED50 values, after i.c.v. administration, initially increased after pellet removal. Because this second manifestation of tolerance occurred during the rapid disappearance of the tolerance-induction drug, it was called withdrawal tolerance. The third manifestation of tolerance, seen after 3 days of pellet implantation, was characterized by the animal's return to a normal nociceptive sensitivity (control tail-flick latency) in the continued presence of the narcotic pellet. Because this adjustment involved an adaptation by the mice to high brain concentrations of narcotic, this third manifestation of tolerance was designated as a physiologic or homeostatic tolerance. The lability of this new homeostatic state (physiologic tolerance) may be associated with an altered sensitivity to naloxone as evidenced by naloxone-induced jumping (precipitated withdrawal).

Topics: Animals; Dose-Response Relationship, Drug; Drug Implants; Drug Tolerance; Etorphine; Heroin; Humans; Male; Methadone; Mice; Morphine; Narcotics; Opioid-Related Disorders; Solubility; Substance Withdrawal Syndrome

Topics: Child Development; Female; Heroin; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Opioid-Related Disorders; Pregnancy; Substance Withdrawal Syndrome

Addicts who use illicit drugs despite receiving a maintenance prescription present a difficult management problem for drug dependence clinics. This study looks at a small group of such addicts and at their response to the provision of a temporary increase in their prescribed opiates. The results indicate that this increase led to a reduction in illicit drug use and to improvements in social functioning. These and other findings are discussed. It is suggested that clinics should be more prepared to consider such temporary increases, but the need for careful monitoring and for the involvement of more than one member of the treatment team is stressed.

Topics: Adult; Alcohol Drinking; Employment; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Methadone; Opioid-Related Disorders; Patient Compliance; Social Behavior

Topics: Adolescent; Black People; Choice Behavior; Codeine; Community Medicine; Crime; Heroin; Humans; Male; Opioid-Related Disorders; White People

The effects of long-acting narcotic agonist preparations on the severe withdrawal syndrome following abrupt cessation of daily injections of codeine phosphate were studied in rats. Twelve hours after the last codeine injections, one injection of either a high or low dose of the zinc tannate salt of heroin, levo-alpha-acetylmethadol (LAAM) or hydromorphone in slow-release vehicle (SRV) was administered. Body weight, core temperature and hyperirritability scores (Teiger, 1974) were recorded every 6 h for the next 3 days. With the exception of the group that received the lower dose of heroin zinc tannate, all drug-treated groups lost significantly less weight than the SRV controls. All rats injected with either LAAM or hydromorphone zinc tannate exhibited prolonged marked hyperthermia, but the low, the high dose heroin groups and the SRV groups showed no significant differences in diurnal temperature patterns. Rats treated with the narcotic agonists were generally less irritable, as indicated by lower Teiger scores. These results indicate that a single injection of heroin, LAAM or hydromorphone zinc tannate can ameliorate the characteristic and intense signs of abstinence following withdrawal from codeine.

Topics: Animals; Behavior, Animal; Body Temperature; Body Weight; Codeine; Delayed-Action Preparations; Heroin; Humans; Hydromorphone; Male; Methadone; Methadyl Acetate; Opioid-Related Disorders; Rats; Substance Withdrawal Syndrome; Zinc

The purpose of this paper is to examine the extent of Dilaudid use and characteristics of users in a population of individuals admitted to drug treatment programs over a four-year period. It was found that the number and rate of Dilaudid use had increased from 1% of those admitted in 1974 to 10% in late 1977. In comparison to other drug users, Dilaudid users were more likely to be white and middle-class. Dilaudid users were also likely to use the drug intravenously and to obtain it by street buys and to also use heroin. Data suggest that Dilaudid use is easily integrated into a heroin-using life style and may serve as a heroin substitute, and that Dilaudid users are a population that has characteristics similar to the type described as the Southern addict.

Topics: Adult; Analgesics, Opioid; Cross-Sectional Studies; Female; Florida; Heroin; Heroin Dependence; Humans; Hydromorphone; Injections, Intramuscular; Injections, Intravenous; Male; Opioid-Related Disorders; Social Class; Socioeconomic Factors; Substance-Related Disorders; Time Factors; White People

Heroin and morphine metabolites can be detected in hair with the use of commercially available radioimmunoassay reagents and with minor sample preparation. Hair samples obtained from morphine-treated mice and heroin users contained nanogram levels of the drug per milligram of hair (single human hair). The results of the hair analyses for all subjects admitting the use of heroin were positive, whereas the results of only 30% of thin-layer chromatographic urinanalyses of these same subjects were positive. In addition, differences in drug concentration for sections of hair near the scalp and near the distal end correlated with the length of time the drug had been used. These results exemplify the potential advantages of the use of hair analysis over urine and serum analyses in terms of accessibility, sample stability, and long-term retention of information.

Topics: Animals; Chromatography, Thin Layer; Forensic Medicine; Hair; Heroin; Heroin Dependence; Humans; Mice; Morphine; Morphine Dependence; Narcotics; Opioid-Related Disorders; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: Cocaine; England; Heroin; Opioid-Related Disorders; Substance-Related Disorders; Toxicology

Topics: Heroin; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Opioid-Related Disorders; Substance-Related Disorders