heroin and Substance-Withdrawal-Syndrome

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

This study's main objective is to carry out a systematic review of the onset of psychotic symptoms after opioid withdrawal. The opiate dependence correlated to psychiatric symptoms has been well described.. Following the PRISMA methodology. The consecutive search strategy was applied: (morphine OR buprenorphine OR oxycodone OR tramadol OR fentanyl OR remifentanil OR opioids OR heroin OR methadone) AND (Psychosis OR psychotic symptoms OR schizophrenia).. 12 case reports, 3 series of cases, 2 clinical studies, and 2 reviews were found. It seems that the time association is present in all of them; symptoms appear days after the interruption of the opioid. Most of the articles reported are case reports that describe symptoms that appear after the suspension of the opioid substance; in most cases, the reintroduction of the opioid had therapeutic effects and provoked a remission of these symptoms. These preliminary findings indicate that opiates could have an antipsychotic effect; however, the literature is scarce. It is critical to consider, if needed, in opioid-dependent patients who start with psychosis after the opioid withdrawal the possible replacement or reintroduction of opioids to prevent further deterioration in the patient's mental status.. This study encompasses a comprehensive description of the literature concerning the possible not well-studied outcome of opioid withdrawal. There are some reports of temporal association between withdrawal and psychotic symptoms that improved after the reintroduction of the opioid; it could be taken into consideration in the clinical practice.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Morphine; Oxycodone; Psychotic Disorders; Substance Withdrawal Syndrome; Tramadol

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

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

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

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

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

Chinese herbal medicine has shown promise for heroin detoxification. This review extends a prior meta-analysis of Chinese herbal medicine for heroin detoxification, with particular attention to the time course of symptoms. Both English and Chinese databases were searched for randomized trials comparing Chinese herbal medicine to either alpha2-adrenergic agonists or opioid agonists for heroin detoxification. The methodological quality of each study was assessed with Jadad's scale (1-2 = low; 3-5 = high). Meta-analysis was performed with fixed- or random-effect models in RevMan software; outcome measures assessed were withdrawal-symptoms score, anxiety, and adverse effects of treatment. Twenty-one studies (2,949 participants) were included. For withdrawal-symptoms score relieving during the 10-day observation, Chinese herbal medicine was superior to alpha2-adrenergic agonists in relieving opioid-withdrawal symptoms during 4-10 days (except D8) and no difference was found within the first 3 days. Compared with opioid agonists, Chinese herbal medicine was inferior during the first 3 days, but the difference became non-significant during days 4-9. Chinese herbal medicine has better effect on anxiety relieving at late stage of intervention than alpha2-adrenergic agonists, and no difference with opioid agonists. The incidence of some adverse effects (fatigue, dizziness) was significantly lower for Chinese herbal medicine than for alpha2-adrenergic agonists (sufficient data for comparison with opioid agonists were not available). Findings were robust to file-drawer effects. Our meta-analysis suggests that Chinese herbal medicine is an effective and safety treatment for heroin detoxification. And more work is needed to determine the specific effects of specific forms of Chinese herbal medicine.

Topics: Adrenergic Agonists; Adult; Anxiety; Drugs, Chinese Herbal; Female; Heroin; Humans; Male; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Treatment Outcome

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

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

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

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

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

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

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

This paper reviews neonatal and developmental behavioral characteristics of children born to heroin- and methadone-addicted women. Evidence of behavioral effects is clearer and more consistent for the neonatal period than in later infancy and childhood. It has not been shown that additional risk for psychological disturbance in childhood is contributed by passive addiction in utero. Methodologic problems in this literature are described and suggestions for strategies and directions in research are offered.

Topics: Child Behavior Disorders; Developmental Disabilities; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome

Topics: Age Factors; Animals; Animals, Suckling; Behavior, Animal; Female; Heroin; Humans; Methadone; Mice; Morphine; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Substance Withdrawal Syndrome; Weaning

Topics: Abnormalities, Drug-Induced; Female; Fetal Alcohol Spectrum Disorders; Fetal Growth Retardation; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Nasopharynx; Phencyclidine; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

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

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

Topics: Alcoholism; Amphetamine; Aversive Therapy; Barbiturates; Heroin; Humans; Lysergic Acid Diethylamide; Methadone; Morphine Dependence; Psychodrama; Psychotherapy; Psychotherapy, Group; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Black or African American; Cannabis; Female; Heroin; Humans; Hypnotics and Sedatives; Lysergic Acid Diethylamide; Male; Middle Aged; Narcotics; Pentazocine; Sex Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents; United States

Topics: Amphetamine; Animals; Autistic Disorder; Behavior, Animal; Catecholamines; Child; Child Behavior; Child Behavior Disorders; Child, Preschool; Chlorpromazine; Clinical Trials as Topic; Dextroamphetamine; Female; Heroin; Humans; Hyperkinesis; Infant, Newborn; Infant, Newborn, Diseases; Learning; Liver; Maternal-Fetal Exchange; Phenothiazines; Placebos; Pregnancy; Pregnancy Complications; Psychopharmacology; Reticular Formation; Schizophrenia, Childhood; Substance Withdrawal Syndrome

Topics: Amphetamine; Antidepressive Agents; Barbiturates; Brain Chemistry; Dreams; Electroconvulsive Therapy; Electroencephalography; Ethanol; Eye Movements; Female; Heroin; Humans; Isocarboxazid; Male; Monoamine Oxidase Inhibitors; Neurons; Nialamide; Phenelzine; Protein Biosynthesis; Reserpine; Sleep; Sleep Stages; Sleep, REM; Substance Withdrawal Syndrome; Tranylcypromine

and purpose: The seeds of Sophora alopecuroides var. alopecuroides have attenuated the acute opium withdrawal syndrome in humans. Therefore, the efficacy and safety of a standardized extract of the plant for the treatment of acute heroin withdrawal syndrome was evaluated in abstinent heroin addicts.. The patients were randomized to take three 400 mg extract capsules (N = 50) or placebo (N = 50) once per day orally for eight days. The severity of withdrawal syndrome was assessed by the clinical opiate withdrawal scale (COWS) as the primary outcome measure at the baseline and on the days 3 and 8. The hepatic and renal functions and complete blood count were the secondary outcome measures tested at the baseline and end of the study.. The COWS score decreased in both groups after eight days, but the decrease was significantly higher in the experimental group (p < 0.001); the effect size of the decrease was 2.64. The groups had significant differences in the COWS scores on the days 3 and 8 (p < 0.001 for both). The extract had no significant effect on the other parameters. No side effect was noted.. The extract seems to alleviate acute heroin withdrawal syndrome safely.

Topics: Animals; Cattle; Female; Heroin; Humans; Seeds; Sophora; Substance Withdrawal Syndrome

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

We assessed the efficacy of pexacerfont, a CRF1 antagonist, for the treatment of withdrawal symptoms. In this randomized, double-blind, placebo-controlled clinical trial, male patients with amphetamine or opioid dependence, on the basis of the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR), in the age range 18-55 years, received either pexacerfont or placebo (300, 200, and 100 mg/day in the first, second, and third week, respectively). No antidepressants, behavioral interventions, or substitution therapy were administered. Candidates were excluded if they had DSM-IV-TR axis I or II disorders (other than depressive/anxiety disorders). The primary outcomes were difference in the distribution of positive urine test results for heroin and methamphetamine at the end of the trial, and the mean difference in the change in the Visual Analog Scale (VAS) score for craving from the baseline to the endpoint between the two groups. No significant difference was detected for urine test results, but a significant difference was observed for craving scores. Also, significant time×treatment interactions were found for all the scales including VAS craving, VAS temptation severity, frequency of temptation, Clinical Opiate Withdrawal Scale, Amphetamine Withdrawal Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory II. Our findings favor pexacerfont as a potential treatment for withdrawal from drug dependence; however, further comprehensive studies are warranted.

Topics: Adult; Central Nervous System Stimulants; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Monitoring; Heroin; Humans; Male; Methamphetamine; Middle Aged; Psychiatric Status Rating Scales; Pyrazoles; Receptors, Corticotropin-Releasing Hormone; Severity of Illness Index; Substance Abuse Detection; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Triazines; Visual Analog Scale

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

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

While exercise has been shown to reduce the negative effects of substance withdrawal symptoms, no research has investigated if Tai Chi, a traditional Chinese exercise, has similar effects. Here, we observed the physiological effects of Tai Chi on protracted abstinence syndrome (PAS) in female heroin addicts by comprehensively inspecting their immune system function, complete blood count, hepatic function and renal function. To determine the psychological effects, we used the Hamilton Rating Scale for Depression (HRSD) and the rating scale of heroin withdrawal symptoms. We recruited 70 heroin-addicted young women beginning to undergo withdrawal and randomly assigned them into two groups: one group received one-hour Tai Chi exercise every two days (Tai Chi group, n = 36) and the other group did not (control group, n = 34). Thirty-three patients finished this six-month trial. Numerous significant physiological differences were observed between all heroin-addicted subjects (n = 70) and age-matched healthy individuals (n = 18), suggesting a deleterious effect of drug addiction. There were improvements for certain physical parameters between the Tai Chi group (n = 17) and the control group (n = 16), although the differences were not statistically significant. We observed a small significant difference in psychological effects near the 60-day mark between the two groups. Taken together, our results suggest that Tai Chi might have a positive effect on PAS, which future studies can confirm by using an expanded sample size, longer trial time, and more sensitive and specific indicators of psychological and physiological health.

Topics: Adult; Female; Heroin; Humans; Substance Withdrawal Syndrome; Tai Ji; 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The purpose of this study was to conduct a cost-effectiveness analysis of detoxification from heroin using buprenorphine in a specialist clinic versus a shared care setting. A randomized controlled trial was conducted with a total of 115 heroin-dependent patients receiving a 5-day treatment regime of buprenorphine. The specialist clinic was a community-based treatment agency in inner-city Sydney. Shared care involved treatment by a general practitioner supplemented by weekend dispensing and some concurrent counselling at the specialist clinic. Quantification of resource use was limited to inputs for treatment provision. The primary outcome measure used in the economic analysis was the proportion of each group that completed detoxification and achieved an initial 7-day period of abstinence. Buprenorphine detoxification in the shared care setting was estimated to be 24 dollars more expensive per patient than treatment at the clinic, which had an average treatment cost of 332 dollars per patient. Twenty-three per cent of the shared care patients and 22% of the clinic patients reported no opiate use during the withdrawal period. These results suggest that the provision of buprenorphine treatment for heroin dependence in shared care and clinic appear to be equally cost-effective.

Topics: Adolescent; Adult; Aged; Buprenorphine; Community Mental Health Services; Cost-Benefit Analysis; Female; Heroin; Humans; Inactivation, Metabolic; Male; Middle Aged; Narcotic Antagonists; Substance Withdrawal Syndrome; Urban Population

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

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

Topics: Adolescent; Adult; Buprenorphine; Capsules; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heroin; Humans; Male; Middle Aged; Phytotherapy; Substance Withdrawal Syndrome

The study aimed to identify the range of buprenorphine doses required to comfortably alleviate symptoms in patients undergoing inpatient heroin withdrawal using a symptom-triggered titration dosing regime, and to identify the patient characteristics that impact upon the buprenorphine dose requirements. The study was conducted in two Australian inpatient withdrawal units, recruiting 63 dependent, injecting heroin users with no recent methadone treatment, dependence on other drugs, or other active medical or psychiatric conditions. In a single (patient) blinded case series, placebo or 2 mg sublingual buprenorphine tablets was administered four times a day according to severity of withdrawal (assessed with Subjective Opiate Withdrawal Scale). Up to 16 mg buprenorphine was available over the first 4 days of the admission, up to 8 mg on day 5, and placebo continued until day 6. Thirty-two subjects completed the dosing regime, with mean (+/-S.D.) daily doses of 3.8+/-2.8 on day 1, 5.8+/-3.2 on day 2, 4.8+/-3.3 on day 3, 2.3+/-2.6 on day 4, 0.8+/-1.3 on day 5, and a total dose of 17.4+/-9.7. Higher buprenorphine doses were required by those patients with more severe psychosocial dysfunction, women, those with more frequent heroin use, and those with more severe dependence on heroin at intake. A dosing regime using sublingual buprenorphine tablets for short inpatient heroin withdrawal is proposed.

Topics: Adolescent; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin; Humans; Male; Middle Aged; Narcotic Antagonists; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Titrimetry

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

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

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

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

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

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

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

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

A sample of 15 patients participating in an injectable methadone trial and of 15 patients in an oral methadone maintenance treatment, who admitted injecting part or all of their methadone take-home doses, were compared to 20 patients in maintenance treatment who use methadone exclusively by mouth. The present study confirms the poorer general health, the higher levels of emotional, psychological or psychiatric problems, the higher use of illicit drugs, and the higher number of problems related to employment and support associated with the use of the intravenous mode of administration of methadone. As expected, due to the shunt of metabolism in the gut wall and of the liver first-pass effect, higher concentration to dose ratios of (R)-methadone, which is the active enantiomer, were measured in the intravenous group (23% increase). This difference reached an almost statistically significant value (P = 0.054). This raises the question whether the effect of a higher methadone dose could be unconsciously sought by some of the intravenous methadone users.

Topics: Administration, Oral; Adult; Brief Psychiatric Rating Scale; Depressive Disorder; Dose-Response Relationship, Drug; Employment; Female; Health Status; Heroin; Humans; Injections, Intravenous; Male; Methadone; Schizophrenia; Self Administration; Severity of Illness Index; Substance Withdrawal Syndrome; Substance-Related Disorders

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

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

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

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

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

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

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

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

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

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

Lofexidine is an analogue of clonidine, an agonist at the alpha 2 noradrenergic receptor. Reports from preliminary open studies have suggested that it may be at least as effective as clonidine in the management of opiate withdrawal, and without the same limitation of postural hypotension. We report on a randomised double-blind comparison of lofexidine versus clonidine in the treatment of heroin withdrawal. A total of 80 hospitalized heroin addicts were randomly assigned to treatment with lofexidine or clonidine during in-patient opiate withdrawal. Maximum daily doses were 1.6 mg for lofexidine and 0.6 mg for clonidine. There was marked diurnal variation of withdrawal symptoms with severity being greatest at the daytime reading at 16.00 h and being markedly less at the night-time reading (recorded at 08.00 h). Lofexidine and clonidine were equally effective in treating the withdrawal syndrome. However, significantly more problems relating to hypotension were encountered with subjects on clonidine, with twice as many instances of withholding medication due to hypotension in the clonidine group. Better treatment retention rates were seen in the lofexidine group, although no difference was found in the proportion who had reached minimal symptom severity by the time of their discharge. We conclude that lofexidine and clonidine are equally effective, but with significantly fewer hypotensive problems with lofexidine. Further benefit from lofexidine may be possible with revised dosing regimens. Outpatient studies of lofexidine are now indicated.

Topics: Adult; Circadian Rhythm; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin; Humans; Hypotension, Orthostatic; Male; Narcotic Antagonists; Severity of Illness Index; Substance Withdrawal Syndrome

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

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

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

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

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

The usefulness of two alpha-2 adrenergic agonists (clonidine and guanfacine) and their comparative effectiveness were evaluated regarding the control of the opiates abstinence syndrome and the secondary effects, including development of cardiovascular abnormalities, in 88 parenteral heroin abusers admitted to two hospital units for the treatment of addiction. The patients were treated in a random, double blind fashion, with clonidine or guanfacine. In the study dosages, both drugs proved to be useful to control the abstinence syndrome. Nearly 70% of those treated with any of the two agonists were able to complete the treatment. When both drugs were compared, a higher degree of restlessness (p less than 0.01) was found among those treated with clonidine, although there were no differences in any other evaluated parameters to compare the degree of abstinence in each drug. The most commonly found side effects were orthostatism, lassitude, mental torpor and oral xerosis. These were independent of the drug used. There were no differences between both drugs regarding heart rate or blood pressure, although both parameters were significantly modified with the doses used in the study.

Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Blood Pressure; Clonidine; Double-Blind Method; Drug Evaluation; Female; Guanfacine; Guanidines; Heart Rate; Heroin; Hospitalization; Humans; Male; Phenylacetates; Random Allocation; Substance Withdrawal Syndrome

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

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

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

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

Topics: Clonidine; Double-Blind Method; Female; Heroin; Hospitalization; Hospitals, General; Humans; Male; Methadone; Methotrimeprazine; Random Allocation; Substance Withdrawal Syndrome

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

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

Clonidine and doxepin alleviate the symptoms of the opiate withdrawal syndrome. Clonidine was slightly more effective in controlling sweating, hot flushes, palpitations and nausea, and doxepin was slightly more effective in relieving the craving for opiates, lassitude and depression. Adverse effects such as sedation, dry mouth and falls in blood pressure occurred in both groups. There were six cases of collapse during treatment with high doses of doxepin, whereas only one subjective circulatory effect occurred in the clonidine group. At these high doses, doxepin may cause orthostatic hypotension via a peripheral alpha-receptor blockade. Clonidine reduced pulse rate whereas doxepin, with its anticholinergic action and indirectly via its alpha-receptor blocking action, raised it. Several patients in the doxepin group hat fits, as opposed to only one in the clonidine group. It is possible that the use of barbiturates had reduced the convulsive threshold in some of our patients. Overall, clonidine and doxepin were equipotent at adequate individual dose levels, and both were well tolerated. In this trial, serious side-effects occurred less often in the clonidine group.

Topics: Adolescent; Adult; Clinical Trials as Topic; Clonidine; Double-Blind Method; Doxepin; Female; Heroin; Humans; Male; Substance Withdrawal Syndrome

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

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

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

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

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Clinical Trials as Topic; Female; Heroin; Humans; Methadone; Nausea; Placebos; Propranolol; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Vomiting

Topics: Acetates; Administration, Oral; Adult; Amino Alcohols; Analysis of Variance; Benzene Derivatives; Clinical Trials as Topic; Codeine; Heroin; Humans; Illinois; Male; Methadone; Methylamines; Middle Aged; Placebos; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Work

Topics: Adult; Alcohols; Amphetamine; Barbiturates; Benzene Derivatives; Heroin; Humans; Injections, Intravenous; Male; Methadone; Methylamines; Morphine; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Animals; Chloral Hydrate; Clinical Trials as Topic; Diazepam; Heroin; Humans; Isonipecotic Acids; Mice; Substance Withdrawal Syndrome

Topics: Alcohols; Clinical Trials as Topic; Heroin; Humans; Methadone; Morphine Dependence; Placebos; Substance Withdrawal Syndrome

Topics: Amphetamine; Animals; Autistic Disorder; Behavior, Animal; Catecholamines; Child; Child Behavior; Child Behavior Disorders; Child, Preschool; Chlorpromazine; Clinical Trials as Topic; Dextroamphetamine; Female; Heroin; Humans; Hyperkinesis; Infant, Newborn; Infant, Newborn, Diseases; Learning; Liver; Maternal-Fetal Exchange; Phenothiazines; Placebos; Pregnancy; Pregnancy Complications; Psychopharmacology; Reticular Formation; Schizophrenia, Childhood; Substance Withdrawal Syndrome

Topics: Chlorpromazine; Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Phenobarbital; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Behavior; Clinical Trials as Topic; Heroin; Humans; Injections, Intravenous; Male; Methods; Morphine; Morphine Dependence; Placebos; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Carfentanil, as a fentanyl analogue, is a potent synthetic opioid. It has been controlled in many countries, and its emergence has been highlighted by many recent reports. However, although discriminative stimulus effects of carfentanil in rats had been reported, its abuse potential has not been fully evaluated. In this study, we evaluated the abuse potential of carfentanil via the tests of conditioned place preference (CPP), drug self-administration and naloxone-precipitated opioid withdrawal assay, compared with fentanyl and heroin. Carfentanil exhibited significant place preference at a minimum dose of 1 μg/kg in mice, whereas fentanyl and heroin induced significant place preference at the minimum doses of 100 μg/kg and 1000 μg/kg, respectively. In the drug-substitution test in heroin self-administered rats (50 μg/kg/infusion), carfentanil and fentanyl acquired significant self-administrations above saline levels from 0.05-0.1 and 0.1-10.0 μg/kg/infusion, respectively. Carfentanil induced the maximum number of infusions at 0.1 μg/kg, whereas fentanyl and heroin at 1 and 25 μg/kg, respectively. In short, carfentanil showed the highest potency to induce CPP and self-administration. Furthermore, repeated treatment with escalating doses of carfentanil, fentanyl or heroin induced typical withdrawal symptoms in mice, including a greater number of jumping and weight loss than saline group. This indicated that carfentanil could produce physical dependence similar to fentanyl and heroin. Taken together, the present study demonstrated the higher abuse potential of carfentanil compared with fentanyl and heroin. The rank order of abuse potential for these compounds is carfentanil > fentanyl > heroin.

Topics: Analgesics, Opioid; Animals; Fentanyl; Heroin; Mice; Naloxone; Rats; Substance Withdrawal Syndrome

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

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

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

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

The aim of the current study was to test the hypothesis that unconditioned and conditioned opioid withdrawal enhance memory consolidation through overlapping neural systems. The reported experiments focussed on noradrenaline (NA) and corticotrophin-releasing factor (CRF) because of their known involvement in both opioid withdrawal and memory consolidation. Male Sprague-Dawley rats were implanted with subcutaneous osmotic mini-pumps releasing 3.5 mg/kg/day heroin and received injections of 3 mg/kg naloxone (NLX) to precipitate withdrawal. NLX was preceded by 0.1-0.6 mg/kg lofexidine (LOF) (alpha-2 adrenergic agonist) or 10-20 mg/kg antalarmin (ANT) (CRF1 receptor antagonist), and all injections were administered immediately after (i.e., post-training method) the sample phase of the spontaneous object recognition memory task. The same procedure was repeated 7 days after removal of the mini-pumps. To establish conditioned withdrawal, heroin-exposed rats were confined for 2 h in a context (CS+) following injections of 3 mg/kg NLX and in another context (CS-) following vehicle injections. Seven days after removal of mini-pumps, the effects of immediate post-sample exposure to the CS+ (and CS-) preceded by 0.6 mg/kg LOF or 20 mg/kg ANT were assessed. It was found both LOF and ANT blocked the enhancement of object memory by post-sample NLX administration and by exposure to the CS+. These results suggest that pharmacological and psychological withdrawal impact memory storage by activating overlapping NA and CRF systems.

Topics: Adrenocorticotropic Hormone; Analgesics, Opioid; Animals; Corticotropin-Releasing Hormone; Heroin; Male; Memory Consolidation; Naloxone; Narcotics; Norepinephrine; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Substance Withdrawal Syndrome

Drug withdrawal elicits immune responses that contribute to the development of withdrawal symptoms and relapse. The understanding of the immunologic dynamics after drug withdrawal is limited, precluding the finding of promising immune intervention measures. Here, we performed cytokine and multiplex immune profiling in heroin, methamphetamine (METH) and ephedrine users after withdrawal and identified the correlation between cytokines and other immune parameters. We showed that broad and strong inflammatory responses occurred at the early stage after drug withdrawal, and the inflammatory responses showed a downtrend with the extension of withdrawal time. Notably, immune dysregulation remained through and may last longer than 12 months after withdrawal in heroin and METH users. Our findings suggest that cytokines, immune cells, complement and immunoglobulin form a complex immune network that regulates immune responses after withdrawal. These data provide a reference for future scientific research and drug research and development.

Topics: Cytokines; Drug Users; Heroin; Humans; Inflammation; Male; Methamphetamine; Substance Withdrawal Syndrome

The development of substance use disorders involves long-lasting adaptations in specific brain areas that result in an elevated risk of relapse. Some of these adaptations are regulated by the mTOR network, a signalling system that integrates extracellular and intracellular stimuli and modulates several processes related to plasticity. While the role of the mTOR network in cocaine- and alcohol-related disorders is well established, little is known about its participation in opiate use disorders.. To use a heroin self-administration and a withdrawal protocol that induce incubation of heroin-seeking in male rats and study the associated effects on the expression of several genes related to the mTOR system and, in the specific case of Rictor, its respective translated protein and phosphorylation.. We found that heroin self-administration elicited an increase in the expression of the genes Igf1r, Igf2r, Akt2 and Gsk3a in the basolateral complex of the amygdala, which was not as evident at 30 days of withdrawal. We also found an increase in the expression of Rictor (a protein of the mTOR complex 2) after heroin self-administration compared to the saline group, which was occluded at the 30-day withdrawal period. The activation levels of Rictor, measured by the phosphorylation rate, were also reduced after heroin self-administration, an effect that seemed more apparent in the protracted withdrawal group.. These results suggest that heroin self-administration under extended access conditions modifies the expression profile of activators and components of the mTOR complexes and show a putative irresponsive mTOR complex 2 after withdrawal from heroin use.

Topics: Amygdala; Animals; Heroin; Male; Rats; Rats, Inbred Lew; Self Administration; Substance Withdrawal Syndrome; TOR Serine-Threonine Kinases

The coronavirus disease 2019 (COVID-19) has highlighted the scope of heroin dependence and need for evidence-based treatment amongst marginalised people in South Africa. Acute opioid withdrawal management without maintenance therapy carries risks of increased morbidity and mortality. Due to the high costs of methadone, Tshwane's Community Oriented Substance Use Programme (COSUP) used tramadol for opioid withdrawal management during the initial COVID-19 response.. To describe demographics, route of heroin administration and medication-related experiences amongst people accessing tramadol for treatment of opioid withdrawal.. Three community-based COSUP sites in Mamelodi (Tshwane, South Africa).. A retrospective cross-sectional study was conducted. Data were collected using an interviewer-administered paper-based tool between April and August 2020. Descriptive statistics were used to analyse data.. Of the 220 service users initiated onto tramadol, almost half (n = 104, 47%) were not contactable. Fifty-eight (26%) people participated, amongst whom most were male (n = 55, 95%). Participants' median age was 32 years. Most participants injected heroin (n = 36, 62.1%). Most participants experienced at least one side effect (n = 47, 81%) with 37 (64%) experiencing two or more side effects from tramadol. Insomnia occurred most frequently (n = 26, 45%). One person without a history of seizures experienced a seizure. Opioid withdrawal symptoms were experienced by 54 participants (93%) whilst taking tramadol. Over half (n = 38, 66%) reported using less heroin whilst on tramadol.. Tramadol reduced heroin use but was associated with withdrawal symptoms and unfavourable side effects. Findings point to the limitations of tramadol as opioid withdrawal management to retain people in care and the importance of access to first-line opioid agonists.Contribution: This research contributes to the limited data around short-acting tramadol for opioid withdrawal management in the African context, with specific focus on the need for increased access to opioid agonists for those who need them, in primary care settings.

Topics: Adult; Analgesics, Opioid; Communicable Disease Control; COVID-19; Cross-Sectional Studies; Female; Heroin; Humans; Male; Methadone; Narcotics; Retrospective Studies; Substance Withdrawal Syndrome; Tramadol

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

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

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

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

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

There is significant comorbidity of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms underlying the relationship between chronic opioid use and withdrawal and development of PTSD are poorly understood. Our previous work identified that chronic escalating heroin administration and withdrawal can produce enhanced fear learning, an animal model of hyperarousal, and is associated with an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β). However, other cytokines, such as TNF-α, work synergistically with IL-1β and may have a role in the development of enhanced fear learning. Based on both translational rodent and clinical studies, TNF-α has been implicated in hyperarousal states of PTSD, and has an established role in hippocampal-dependent learning and memory. The first set of experiments tested the hypothesis that chronic heroin administration followed by withdrawal is capable of inducing alterations in DH TNF-α expression. The second set of experiments examined whether DH TNF-α expression is functionally relevant to the development of enhanced fear learning. We identified an increase of TNF-α immunoreactivity and positive cells at 0, 24, and 48 h into withdrawal in the dentate gyrus DH subregion. Interestingly, intra-DH infusions of etanercept (TNF-α inhibitor) 0, 24, and 48 h into heroin withdrawal prevented the development of enhanced fear learning and mitigated withdrawal-induced weight loss. Overall, these findings provide insight into the role of TNF-α in opioid withdrawal and the development of anxiety disorders such as PTSD.

Topics: Animals; Etanercept; Fear; Heroin; Hippocampus; Learning; Male; Rats, Sprague-Dawley; Signal Transduction; Substance Withdrawal Syndrome; Tumor Necrosis Factor-alpha; Weight Loss

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

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

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

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

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

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

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

Converging evidence suggests opioid abuse can increase the incidence and severity of post-traumatic stress disorder (PTSD) in clinical populations. Interestingly, opioid withdrawal alone can produce symptoms similar to those of PTSD. Despite this association, the neural mechanisms underlying the relationship of opioid abuse, withdrawal, and PTSD is poorly understood. Our laboratory has investigated the neurobiological underpinnings of stress-enhanced fear learning (SEFL), an animal model of PTSD-like symptoms. We have previously shown that, in SEFL, a severe footshock induces an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β), and subsequent fear learning is blocked by DH IL-1 receptor antagonism (IL-1RA). Given that opioids and stress engage similar neuroimmune mechanisms, the present experiments investigate whether the same mechanisms drive heroin withdrawal to induce a PTSD-like phenotype. First, we tested the effect of a chronic escalating heroin dose and withdrawal regimen on fear learning and found it produces enhanced future fear learning. Heroin withdrawal also induces a time-dependent, region-specific increase in IL-1β and glial fibrillary acidic protein (GFAP) immunoreactivity within the dentate gyrus of the DH. IL-1β was significantly colocalized with GFAP, indicating astrocytes may be involved in increased IL-1β. Moreover, intra-DH infusions of IL-1RA 0, 24, and 48 h into heroin withdrawal prevents the development of enhanced fear learning but does not alter withdrawal-induced weight loss. Collectively, our data suggests heroin withdrawal is sufficient to produce enhanced fear learning, astrocytes may play a role in heroin withdrawal-induced IL-1β, and DH IL-1 signaling during withdrawal mediates the development of heroin withdrawal-enhanced fear learning.

Topics: Analgesics, Opioid; Animals; Fear; Heroin; Hippocampus; Interleukin-1beta; Learning; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Substance Withdrawal Syndrome

Electroacupuncture (EA) has effective analgesic effects. Our previous study demonstrated that the upregulation of P2X3 receptors in the dorsal root ganglia (DRG) might participate in heroin withdrawal-induced hyperalgesia. The aim of this study is to further explore whether 2 Hz EA reduces heroin relapse associated with its analgesic effect and whether P2X3 receptors in the DRG are involved in this process. 2 Hz EA was adopted to treat the heroin SA rats in the present study. Heroin-seeking and pain sensitivity were evaluated. The expression of P2X3 receptors in the DRG was detected. Our results showed that compared with the control group, the reinstatement, thermal hyperalgesia, and mechanical allodynia of the heroin-addicted group were increased significantly. The expression of P2X3 receptors in the DRG was increased markedly. After being treated using 2 Hz EA, reinstatement was reduced, hyperalgesia was decreased, and the upregulated expression of P2X3 receptors in the DRG had decreased significantly compared to that in the heroin-addicted group. Consequently, our results indicated that 2 Hz EA was an effective method for treating heroin-induced hyperalgesia and helping prevent relapse, and the potential mechanism might be related to the downregulation of P2X3 receptor expression in the DRG.

Topics: Animals; Electroacupuncture; Ganglia, Spinal; Gene Expression Regulation; Heroin; Hyperalgesia; Neuralgia; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2X3; Substance Withdrawal Syndrome

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

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

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

Skin and soft tissue infections (SSTIs) are prevalent among people who inject heroin (PWIH). Delays in seeking health care lead to increased costs and potential mortality, yet the barriers to accessing care among PWIHs are poorly understood.. We administered a quantitative survey (N = 145) and conducted qualitative interviews (N = 12) with PWIH seeking syringe exchange services in two U.S. cities.. 66% of participants had experienced at least one SSTI. 38% reported waiting two weeks or more to seek care, and 57% reported leaving the hospital against medical advice. 54% reported undergoing a drainage procedure performed by a non-medical professional, and 32% reported taking antibiotics that were not prescribed to them. Two of the most common reasons for these behaviors were fear of withdrawal symptoms and inadequate pain control, and these reasons emerged as prominent themes in the qualitative findings. These issues are often predicated on previous negative experiences and exacerbated by stigma and an asymmetrical power dynamic with providers, resulting in perceived barriers to seeking and completing care for SSTIs.. For PWIH, unaddressed pain and withdrawal symptoms contribute to profoundly negative health care experiences, which then generate motivation for delaying care SSTI seeking and for discharge against medical advice. Health care providers and hospitals should develop policies to improve pain control, manage opioid withdrawal, minimize prejudice and stigma, and optimize communication with PWIH. These barriers should also be addressed by providing medical care in accessible and acceptable venues, such as safe injection facilities, street outreach, and other harm reduction venues.

Topics: Abscess; Adult; Cross-Sectional Studies; Female; Heroin; Humans; Male; Middle Aged; Pain; Pain Management; Patient Acceptance of Health Care; Prejudice; Retrospective Studies; Social Stigma; Soft Tissue Infections; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

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

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal.

Topics: Animals; Brain-Derived Neurotrophic Factor; Heroin; Nerve Growth Factors; Neurotrophin 3; Rats, Sprague-Dawley; RNA, Messenger; Substance Withdrawal Syndrome

BACKGROUND The aim of this study was to explore how changes in the expression of BDNF in MLDS change the effect of BDNF on dopamine (DA) neurons, which may have therapeutic implications for heroin addiction. MATERIAL AND METHODS We established a rat model of heroin addiction and observed changes in the expression of BDNF, DA, dopamine receptor (DRD), dopamine transporter (DAT), and other relevant pathways in NAc. We also assessed the effect of BDNF overexpression in the NAc, behavioral changes of heroin-conditioned place preference (CPP), and naloxone withdrawal in rats with high levels of BDNF. We established 5 adult male rat groups: heroin addiction, lentivirus transfection, blank virus, sham operation, and control. The PCR gene chip was used to study gene expression changes. BDNF lentivirus transfection was used for BDNF overexpression. A heroin CPP model and a naloxone withdrawal model of rats were established. RESULTS Expression changes were found in 20 of the 84 DA-associated genes in the NAc of heroin-addicted rats. Weight loss and withdrawal symptoms in the lentivirus group for naloxone withdrawal was less than in the blank virus and the sham operation group. These 2 latter groups also showed significant behavioral changes, but such changes were not observed in the BDNF lentivirus group before or after training. DRD3 and DAT increased in the NAc of the lentivirus group. CONCLUSIONS BDNF and DA in the NAc are involved in heroin addiction. BDNF overexpression in NAc reduces withdrawal symptoms and craving behavior for medicine induced by environmental cues for heroin-addicted rats. BDNF participates in the regulation of the dopamine system by acting on DRD3 and DAT.

Topics: Animals; Brain-Derived Neurotrophic Factor; Dopamine; Dopamine Plasma Membrane Transport Proteins; Gene Expression Regulation; Heroin; Male; Nucleus Accumbens; Plasmids; Rats, Sprague-Dawley; Receptors, Dopamine; Sequence Analysis, DNA; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Tyrosine 3-Monooxygenase

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

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

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

Kratom use in the West has increased recently, yet the prevalence and motives for use among individuals with a history of substance use disorder (SUD) have not been fully examined. Kratom has been documented as a means of treating chronic pain, mitigating drug dependence, and easing withdrawal symptoms, yet it is unclear if substance users are utilizing kratom as a self-medication. Abuse liability, side effects, and overall appeal of kratom remain uncertain.. In April 2017, an anonymous survey regarding kratom use and motivations was completed by clients enrolled in a 12-Step-oriented residential program. 500 respondents with a self-reported history of SUD completed the survey.. 20.8% of respondents endorsed lifetime kratom use and 10.2% reported past-12-month use. Kratom-users were younger (=32.1 vs. 35.9, p<0.001) and were more versatile substance users. A majority (68.9%) of kratom-users reported having used the drug as a means of reducing or abstaining from non-prescription opioids (NPO) and/or heroin, and 64.1% reported using kratom as a substitute for NPO/heroin. 18.4% of kratom-users reported using the drug due to a disability or chronic pain. One-third of kratom-users stated that kratom was a helpful substance and that they would try it again. However, kratom was not preferred and was indicated as having less appeal than NPO, heroin, amphetamines, and Suboxone.. Among substance users, kratom use may be initiated for a variety of reasons, including as a novel form of harm-reduction or drug substitution, particularly in the context of dependence and withdrawal from other substances.

Topics: Amphetamines; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Heroin; Humans; Motivation; Prevalence; Residential Treatment; Self Medication; Self Report; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

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 mammalian basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) comprise a functionally interconnected circuit that is critical for processing opiate-related associative memories. In the opiate-naïve state, reward memory formation in the BLA involves a functional link between dopamine (DA) D1 receptor (D1R) and extracellular signal-related kinase 1/2 (ERK1/2) signaling substrates, but switches to a DA D2 (D2R)/Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα)-dependent memory substrate following chronic opiate exposure and spontaneous withdrawal. Using conditioned place preference (CPP) in rats paired with molecular analyses, we examined the role of intra-mPFC CaMKII, ERK and DAergic activity during the formation of opiate associative memories, and how opiate exposure state may regulate the functions of these molecular memory pathways. We report that the role of CaMKIIα signaling is functionally reversed within the BLA-mPFC pathway depending on opiate exposure state. Thus, in the opiate-naïve state, intra-mPFC but not intra-BLA blockade of CaMKII signaling prevents formation of opiate reward memory. However, following chronic opiate exposure and spontaneous withdrawal, the role of CaMKII signaling in the BLA-mPFC is functionally reversed. This behavioral memory switch corresponds to a selective increase in the expression of D2R and CaMKIIα, but not other calcium/calmodulin-related molecules, nor D1R expression levels within the mPFC.

Topics: Amygdala; Analgesics, Opioid; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Conditioning, Psychological; Heroin; Male; Memory; Neural Pathways; Prefrontal Cortex; Random Allocation; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Signal Transduction; Spatial Behavior; Substance Withdrawal Syndrome

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

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

It has been suggested that withdrawal from sugar produces a set of symptoms that resemble those observed following withdrawal from opiate drugs.. This study explored naltrexone-induced withdrawal in animals pre-exposed to acute, chronic, and intermittent high fructose corn syrup (HFCS) or acute and chronic heroin administration.. Experiment 1 examined conditioned place avoidance (CPA) induced by different doses of naltrexone (0.01-1 mg/kg) in naïve male Sprague-Dawley rats. In experiment 2, rats received continuous or intermittent home cage HFCS access (0 or 50 %) prior to conditioning with 1 mg/kg naltrexone. In experiment 3, HFCS ingestion was increased by food restriction and rats were conditioned with 3 mg/kg naltrexone. In experiment 4, the timing and quantity of HFCS ingestion (0, 0.5, 1, 2 g/kg) was controlled by intragastric administration, and rats were conditioned with 1 mg/kg naltrexone. In experiment 5, rats received acute (2 mg/kg) or chronic heroin (3.5 mg/kg/day) prior to conditioning with 1 mg/kg naltrexone.. Administration of naltrexone produced moderate conditioned place avoidance in naïve rats. Importantly, acute, continuous, and intermittent HFCS pre-exposure did not significantly amplify this effect, but acute and chronic heroin pre-exposure did.. As assessed by CPA, these results in rats fail to support the hypothesis that an opioid antagonist can precipitate similar affective withdrawal states following pre-exposure to sugars and opiates.

Topics: Animals; Avoidance Learning; Conditioning, Operant; Dose-Response Relationship, Drug; Food Deprivation; Heroin; High Fructose Corn Syrup; Naltrexone; Narcotic Antagonists; Narcotics; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome

The present study was designed to investigate the effect of a methanolic extract of Morinda citrifolia Linn. fruit (MMC) on the rewarding effect of heroin in the rat conditioned place preference (CPP) paradigm and naloxone-precipitated withdrawal in mice. In the first experiment, following a baseline preference test (preconditioning score), the rats were subjected to conditioning trials with five counterbalanced escalating doses of heroin versus saline followed by a preference test conducted under drug-free conditions (post-conditioning score) using the CPP test. Meanwhile, in the second experiment, withdrawal jumping was precipitated by naloxone administration after heroin dependence was induced by escalating doses for 6 days (3×/ day). The CPP test results revealed that acute administration of MMC (1, 3, and 5 g/kg body weight (bw), p.o.), 1 h prior to the CPP test on the 12th day significantly reversed the heroin-seeking behavior in a dose-dependent manner, which was similar to the results observed with a reference drug, methadone (3 mg/kg bw, p.o.). On the other hand, MMC (0.5, 1, and 3 g/kg bw, p.o.) did not attenuate the heroin withdrawal jumps precipitated by naloxone. These findings suggest that the mechanism by which MMC inhibits the rewarding effect of heroin is distinct from naloxone-precipitated heroin withdrawal.

Topics: Animals; Behavior, Animal; Conditioning, Psychological; Fruit; Heroin; Male; Mice, Inbred ICR; Models, Animal; Morinda; Naloxone; Plant Extracts; Rats, Sprague-Dawley; Reinforcement, Psychology; Reward; Substance Withdrawal Syndrome; Substance-Related Disorders

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

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

The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence.

Topics: Animals; Central Amygdaloid Nucleus; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking Behavior; Drug-Seeking Behavior; Feeding Behavior; Heroin; Heroin Dependence; Locomotion; Male; Narcotics; Orexin Receptor Antagonists; Orexin Receptors; Rats, Wistar; RNA, Messenger; Self Administration; Substance Withdrawal Syndrome; Time Factors

Opiate addiction is a brain disorder emerging through repeated intoxication and withdrawal episodes. Epidemiological studies also indicate that chronic exposure to opiates may lead in susceptible individuals to the emergence of depressive symptoms, strongly contributing to the severity and chronicity of addiction. We recently established a mouse model of heroin abstinence, characterized by the development of depressive-like behaviors following chronic heroin exposure.. While genetic factors regulating immediate behavioral responses to opiates have been largely investigated, little is known about their contribution to long-term emotional regulation during abstinence. Here, we compared locomotor stimulation and physical dependence induced by heroin exposure, as well as emotional dysfunction following abstinence, across mice strains with distinct genetic backgrounds.. Mice from three inbred strains (C57BL/6J, Balb/cByJ, and 129S2/SvPas) were exposed to an escalating chronic heroin regimen (10-50 mg/kg). Independent cohorts were used to assess drug-induced locomotor activity during chronic treatment, naloxone-precipitated withdrawal at the end of chronic treatment, and emotional-like responses after a 4-week abstinence period.. Distinct behavioral profiles were observed across strains during heroin treatment, with no physical dependence and low locomotor stimulation in 129S2/SvPas. In addition, different behavioral impairments developed during abstinence across the three strains, with increased despair-like behavior in 129S2/SvPas and Balb/cByJ, and low sociability in 129S2/SvPas and C57BL/6J.. Our results indicate that depressive-like behaviors emerge during heroin abstinence, whatever the severity of immediate behavioral responses to the drug. In addition, inbred mouse strains will allow studying several aspects of mood-related deficits associated with addiction.

Topics: Animals; Arousal; Emotions; Heroin; Heroin Dependence; Male; Mice; Mice, Inbred Strains; Motor Activity; Naloxone; Social Behavior; Substance Withdrawal Syndrome

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

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

To analyse drug users' views and experiences of naloxone during emergency resuscitation after illicit opiate overdose to identify (i) any evidence of harm caused by excessive naloxone dosing ('over-antagonism'); and (ii) implications for the medical administration of naloxone within contemporary emergency settings.. Re-analysis of a large qualitative data set comprising 70 face-to-face interviews conducted within a few hours of heroin/opioid overdose occurring, observations from hospital settings and a further 130 interviews with illicit opiate users. Data were generated between 1997 and 1999.. Emergency departments, drug services and pharmacies in two Scottish cities.. Two hundred illicit opiate users: 131 males and 69 females.. Participants had limited knowledge of naloxone and its pharmacology, yet described it routinely in negative terms and were critical of its medical administration. In particular, they complained that naloxone induced acute withdrawal symptoms, causing patients to refuse treatment, become aggressive, discharge themselves from hospital and take additional street drugs to counter the naloxone effects. Participants believed that hospital staff should administer naloxone selectively and cautiously, and prescribe counter-naloxone medication if dosing precipitated withdrawals. In contrast, observational data indicated that participants did not always know that they had received naloxone and hospital doctors did not necessarily administer it incautiously.. Opiate users in urban Scotland repeatedly report harm caused by naloxone over-antagonism, although this is not evident in observational data. The concept of contemporary legend (a form of folklore that can be based on fact and provides a means of communicating and negotiating anxiety) helps to explain why naloxone has such a feared reputation among opiate users.

Topics: Adolescent; Adult; Analgesics, Opioid; Drug Overdose; Emergency Service, Hospital; Emergency Treatment; Female; Heroin; Humans; Iatrogenic Disease; Male; Middle Aged; Naloxone; Narcotic Antagonists; Patient Satisfaction; Qualitative Research; Scotland; Substance Withdrawal Syndrome; Treatment Refusal; Young Adult

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction.

Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Behavior, Animal; Benzazepines; Central Nervous System Stimulants; Clonidine; Heroin; Male; Mice; Motor Activity; Naloxone; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Substance Withdrawal Syndrome

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer.

Topics: Adult; Delay Discounting; Emotional Intelligence; Female; Heroin; Heroin Dependence; Humans; Impulsive Behavior; Intelligence; Male; Middle Aged; Reward; Substance Withdrawal Syndrome; Young Adult

It has been proposed that relapse vulnerability in previously dependent individuals results from augmentation of drug-induced reinforcement due to repeated associations between the interoceptive properties of the drug and reduction of acute withdrawal distress.. To test this hypothesis, male Sprague-Dawley rats self-administered 0.05 mg/kg/inf heroin on continuous reinforcement (CR) and progressive ratio (PR) schedules. During this period, they also received injections of vehicle or escalating doses of heroin. Following tests of naloxone-precipitated withdrawal, as well as a drug-free period (4 days), and extinction (9 sessions), they were pre-treated with vehicle or yohimbine (0.5mg/kg, IV) and tested for resumption of heroin self-administration (0.05 mg/kg/inf) on CR and PR schedules, or tested for reinstatement in extinction conditions.. Increased self-administration on the CR schedule was observed in the heroin-injected rats, but no group differences were observed on the PR schedule, in spite of greater signs of withdrawal precipitated by naloxone in the heroin-injected rats. More importantly, there were no group differences in resumption of heroin self-administration, and this was not altered by yohimbine.. These results suggest that relapse vulnerability cannot be uniquely ascribed to enhanced reinforcing action of drugs; contextual and other conditioning factors must play a role in modulating resumption of drug intake after abstinence.

Topics: Animals; Dose-Response Relationship, Drug; Extinction, Psychological; Heroin; Heroin Dependence; Male; Naloxone; Rats; Reinforcement Schedule; Self Administration; Substance Withdrawal Syndrome; Yohimbine

Topics: Health Resources; Heroin; Heroin Dependence; Humans; Nursing Homes; Opiate Substitution Treatment; Patient Care Team; Rehabilitation Centers; Substance Withdrawal Syndrome; Switzerland

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of opiate addiction. Both increased and decreased serum BDNF levels have been reported in heroin addicts. Moreover, the role of BDNF in heroin-dependent patients during withdrawal has not been studied. This study aimed to explore the differences in serum BDNF levels of heroin addicts and healthy controls, and investigate the changes of serum BDNF levels in heroin addicts at baseline and at one month after heroin cessation. Seventy-two heroin-dependent patients and ninety age- and gender-matched healthy controls were enrolled in this study. We measured serum BDNF levels at baseline (both heroin addicts and healthy controls) and one month after heroin cessation (heroin addicts only). A total of 37 (51.4%) heroin addicts completed the one-month study. We found that baseline serum BDNF levels were significantly higher in heroin addicts compared to controls (F=36.5, p=0.001). There was no difference in serum BDNF levels among heroin addicts at baseline and one month after heroin cessation (F=1.101, p=0.301). These results indicate that BDNF may play a critical role in the course of opiate addiction and withdrawal.

Topics: Adult; Brain-Derived Neurotrophic Factor; Case-Control Studies; Female; Heroin; Heroin Dependence; Humans; Male; Substance Withdrawal Syndrome

Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse.

Topics: Animals; Antidepressive Agents, Second-Generation; Depression; Disease Models, Animal; Dorsal Raphe Nucleus; Fluoxetine; Heroin; Heroin Dependence; Male; Memory Disorders; Memory, Short-Term; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Narcotics; Receptors, Opioid, kappa; Receptors, Opioid, mu; Social Behavior; Spatial Memory; Substance Withdrawal Syndrome

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

Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats.. Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks. The selective mGluR5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 5, 15 and 50 nmol per side) was then microinjected into the NAc core or shell 10 min before a heroin-seeking test induced by context, cues or heroin priming.. Microinjection of MPEP into the NAc shell dose-dependently decreased the heroin seeking induced by context, cues or heroin priming. In contrast, microinjection of MPEP into the NAc core did not alter the heroin seeking induced by cues or heroin priming. In addition, microinjection with MPEP (15 nmol per side) in the NAc shell reversed both the percentage of open arms entries (OE%) and the percentage of time spent in open arms (OT%) after heroin withdrawal. Microinjection of MPEP (50 nmol per side) in the striatum as a control location did not affect the heroin seeking behavior. Microinjection of MPEP in the 3 locations did not change the locomotion activities.. Blockade of mGluR5 in NAc shell in rats specifically suppresses the relapse to heroin-seeking and anxiety-like behavior, suggesting that mGluR5 antagonists may be a potential candidate for the therapy of heroin addiction.

Topics: Analgesics, Opioid; Animals; Anxiety; Behavior, Animal; Cues; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Excitatory Amino Acid Antagonists; Heroin; Heroin Dependence; Locomotion; Male; Nucleus Accumbens; Pyridines; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5; Recurrence; Self Administration; Substance Withdrawal Syndrome; Time Factors

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

Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

Topics: Acoustic Stimulation; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Analysis of Variance; Animals; Clonidine; Conditioning, Operant; Corticotropin-Releasing Hormone; Disease Models, Animal; Heroin; Male; Narcotics; Norepinephrine; Psychoacoustics; Pyrimidines; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2; Reflex, Startle; Self Administration; Substance Withdrawal Syndrome; Time Factors; Yohimbine

It is known that heroin dependence and withdrawal are associated with changes in the hypothalamic-pituitary-adrenal (HPA) axis. The objective of these studies in rats was to systematically investigate the level of HPA activity and response to a heroin challenge at two time points during heroin withdrawal, and to characterize the expression of associated stress-related genes 30 min after each heroin challenge. Rats received chronic (10-day) intermittent escalating-dose heroin administration (3 × 2.5 mg/kg/day on day 1; 3 × 20 mg/kg/day by day 10). Hormonal and neurochemical assessments were performed in acute (12 h after last heroin injection) and chronic (10 days after the last injection) withdrawal. Both plasma ACTH and corticosterone levels were elevated during acute withdrawal, and heroin challenge at 20 mg/kg (the last dose of chronic escalation) at this time point attenuated this HPA hyperactivity. During chronic withdrawal, HPA hormonal levels returned to baseline, but heroin challenge at 5 mg/kg decreased ACTH levels. In contrast, this dose of heroin challenge stimulated the HPA axis in heroin naïve rats. In the anterior pituitary, pro-opiomelanocortin (POMC) mRNA levels were increased during acute withdrawal and retuned to control levels after chronic withdrawal. In the medial hypothalamus, however, the POMC mRNA levels were decreased during acute withdrawal, and increased after chronic withdrawal. Our results suggest a long-lasting change in HPA abnormal responsivity during chronic heroin withdrawal.

Topics: Acute Disease; Adrenocorticotropic Hormone; Animals; Chronic Disease; Corticosterone; Heroin; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Pro-Opiomelanocortin; Rats; Rats, Inbred F344; Substance Withdrawal Syndrome

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

Topics: Administration, Inhalation; Adult; Echocardiography; Electrocardiography; Heroin; Humans; Male; Myocardial Stunning; Narcotics; Substance Withdrawal Syndrome; Takotsubo Cardiomyopathy

Topics: Arrhythmias, Cardiac; Excitatory Amino Acid Antagonists; Heroin; Humans; Ibogaine; Male; Narcotics; Self Medication; Substance Withdrawal Syndrome; Young Adult

Heroin addiction is characterized by recurrent cycles of drug use, abstinence, and relapse. It is likely that neurobiological changes during chronic heroin exposure persist across withdrawal and impact behavioral responses to re-exposure. We hypothesized that, after extended withdrawal, heroin-withdrawn rats would express behavioral tolerance and/or sensitization in response to heroin re-exposure and that these responses might be associated with altered mu-opioid receptor (MOPr) activity.. Male Fischer rats were exposed chronically to escalating doses of heroin (7.5-75 mg/kg/day), experienced acute spontaneous withdrawal and extended (10-day) abstinence, and were re-exposed chronically to heroin. Homecage behaviors and locomotor activity in response to heroin, as well as somatic withdrawal signs, were recorded. Separate groups of rats were sacrificed after extended abstinence and MOPr expression and G-protein coupling were analyzed using [(3)H]DAMGO and [(35)S]GTPγS assays.. The depth of behavioral stupor was lower during the initial days of heroin re-exposure compared to the initial days of the first exposure period. Behavioral responses (e.g., stereotypy) and locomotion were elevated in response to heroin re-exposure at low doses. Rats conditioned for heroin place preference during the chronic re-exposure period expressed heroin preference during acute withdrawal; this preference was stronger than rats conditioned during chronic heroin exposure that followed chronic saline and injection-free periods. Extended withdrawal was associated with increased MOPr expression in the caudate-putamen and frontal and cingulate cortices. No changes in G-protein coupling were identified.. Aspects of tolerance/sensitization to heroin are present even after extended abstinence and may be associated with altered MOPr density.

Topics: Animals; Behavior, Addictive; Behavior, Animal; Dose-Response Relationship, Drug; Drug Tolerance; Heroin; Heroin Dependence; Male; Motor Activity; Rats; Rats, Inbred F344; Receptors, Opioid, mu; Substance Withdrawal Syndrome

Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely correlates of sensitivity to behavioral reinforcement in rats: physical withdrawal and locomotor sensitization.. Adolescent (35 days old at start) and adult (79 days old) male Sprague-Dawley rats were administered escalating doses of heroin, increasing from 1.0 to 8.0 mg/kg (i.p.) every 12 h, across 13 days. Somatic signs of spontaneous withdrawal were scored 12 and 24 h after the last injection, and then every 24 h for 5 days; locomotion was recorded concurrently. Challenge injections of heroin (1 mg/kg i.p.) were given at four points: as the first of the escalating doses (day 1), at days 7 and 13 during the escalating regimen, and after 12 days of forced abstinence. Body mass and food intake were measured throughout experimentation.. A heroin withdrawal syndrome was not observed among adolescents as it was among adults, including somatic signs as well as reduced locomotion, body mass, and food intake. On the other hand, heroin-induced locomotor sensitization did not differ across ages.. Reduced withdrawal is consistent with the attenuated reinforcing effects of heroin among adolescent male rats that we reported previously. Thus, it is possible that adolescent rats could reveal important neuroprotective factors for use in treatment of heroin dependence.

Topics: Aging; Animals; Body Weight; Dose-Response Relationship, Drug; Eating; Heroin; Heroin Dependence; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome

In humans, hyperalgesia, tolerance and anxiety disorders are common symptoms during heroin withdrawal syndrome. Significant evidence supports a role of NMDA receptors in these phenomena. Because polyamines may positively modulate the functioning of NMDA receptors and mainly originate from dietary intake, one hypothesis is that a polyamine deficient diet (PD diet) may reduce withdrawal symptoms. To address this question, we investigated the ability of a PD diet to prevent or to alleviate some symptoms of withdrawal syndrome as hyperalgesia, and increased anxiety-like behaviour in rats receiving 14 once daily subcutaneous heroin injections. Here, we show that a PD diet has both preventive and curative properties for reducing certain signs of withdrawal such as hyperalgesia, tolerance and increased anxiety-like behaviour observed in rats fed with a standard diet. Moreover, in heroin-withdrawn rats which were returned to basal pain sensitivity level, hyperalgesia following acute analgesia induced by a single heroin dose was observed in heroin-treated rats fed with standard diet, not in rats fed with a PD diet. Similarly, a stress-induced hyperalgesia induced by a non-nociceptive environmental stress session was observed in heroin-treated rats fed with standard diet. In contrast, a stress-induced analgesia was observed in heroin-treated rats fed with a PD diet, as it was observed in non heroin-treated rats. Since a PD diet for several weeks did not induce appreciable side-effects in rats, these preclinical results suggest that a PD diet could be an effective strategy for improving the relief of certain negative emotional states of heroin withdrawal syndrome and to allow reducing other medications generally used, such as opioid maintenance drugs.

Topics: Analgesics, Opioid; Animals; Anxiety; Diet; Disease Models, Animal; Drug Tolerance; Heroin; Hyperalgesia; Male; Maze Learning; Memory, Short-Term; Motor Activity; Pain Measurement; Polyamines; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome

To date, it has been difficult to address the issue of sexual functioning and drug use, and many approaches to it have basic problems and methodological errors.. The present cross-sectional study compared the sexual functioning scores of a group of drug users with those of a group of nondrug users. It explored the relationship between drug abstinence and sexual functioning.. A sample of 905 males participated in this study (549 met the substance dependence criteria and 356 were controls). All of them were assessed with the Changes in Sexual Functioning Questionnaire-Drugs version.. The assessment was conducted from September 2009 to January 2011. The clinical sample was evaluated in nine different substance abuse treatment facilities.. Results show that, overall, all dimensions (pleasure, desire, arousal, and orgasm) were moderately impaired. Yet, differences regarding preferred substance were observed. Pleasure and orgasm were the two areas most significantly impaired. In these areas, all drugs seemed to negatively affect sexual functioning. However, desire and arousal were not affected by all the substances. In addition, at least after 2 weeks of drug abstinence, no relationship was found between drug abstinence and improvement in sexual functioning. The sample studied had an average of 1 year of drug abstinence and was found to have poorer sexual functioning than the control group.. Therefore, these results seem to contradict those that argue that drug use only impairs sexual functioning temporarily. Moreover, they suggest that sexual functioning does not improve just by stopping drug use.

Topics: Adult; Alcoholism; Arousal; Cocaine; Drug Synergism; Ethanol; Follow-Up Studies; Heroin; Humans; Illicit Drugs; Libido; Male; Middle Aged; Orgasm; Pleasure; Sexual Dysfunction, Physiological; Sexuality; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Substance-Related Disorders

Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin's incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence.. Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals' behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded.. Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs.. Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior.

Topics: Animals; Behavior, Addictive; Conditioning, Psychological; Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Male; Motivation; Rats; Rats, Inbred F344; Substance Withdrawal Syndrome

Drug-dependent people exhibit biases when evaluating discrete emotional facial expressions. Little is known about how drug abusers process multiple expressions presented simultaneously. The present study investigated the number perception of schematic emotional expressions by abstinent heroin abusers.. Eighty-four heroin abstainers with varied lengths of abstinence (short-term, mid-term, and long-term) and twenty healthy controls were examined. A method of limits was deployed to obtain estimates (points of subjective equality) of perceived numbers of schematic faces (expressing positive, neutral, or negative emotion).. Major results include the following: 1) heroin-abstinent participants showed significantly lower points of subjective equality for negative and neutral faces, but not for positive faces, compared to control participants; 2) heroin-abstinent participants showed lower points of subjective equality for negative faces and higher ones for positive faces when compared to neutral faces, while no such differences were found in control participants.. Heroin abusers demonstrate an exaggerated perception of number when exposed to negative expressions, even after a period of abstinence as long as 10 months. In addition, the current results could also reflect an underestimated perception of number during exposure to positive expressions and a heightened baseline for neutral expressions, or the attribution of negative valence to neutral expressions by heroin abusers.

Topics: Adult; Emotions; Facial Expression; Female; Heroin; Humans; Male; Mathematics; Pattern Recognition, Visual; Perceptual Disorders; Photic Stimulation; Substance Withdrawal Syndrome; Time Factors; Young Adult

Evidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues.. Rats were trained to self-administer heroin for 12 days, underwent extinction training for 12 days followed by two weeks in their home cages. Then the conditioned cues were introduced for the reinstatement of heroin-seeking.. The reinstatement of heroin-seeking induced by cues was attenuated by the administration of galantamine (0, 0.3, 1 or 3mg/kg, i.p.) in a dose-dependent manner. In contrast, galantamine only at the dose of 3mg/kg could inhibit the reinstatement of sucrose-seeking. Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats. The inhibition of drug-seeking by galantamine was reversed by pretreatment with scopolamine (0.5mg/kg) but not with mecamylamine (3mg/kg) or scopolamine methobromide (1mg/kg). Moreover, the microinjection of galantamine into the LDT blocked cue-induced heroin-seeking, while the microinjection of scopolamine into the LDT reversed the inhibitory effect of galantamine on drug-seeking behavior.. The results suggest that cholinergic transmission in the LDT may play a critical role in heroin-seeking behavior induced by cues and that galantamine may have the beneficial effect of blocking heroin-seeking behavior, which is mediated through its actions on the muscarinic receptors.

Topics: Animals; Behavior, Animal; Cholinergic Antagonists; Cholinesterase Inhibitors; Cues; Drug-Seeking Behavior; Extinction, Psychological; Galantamine; Heroin; Mecamylamine; Motor Activity; Narcotics; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Scopolamine; Self Administration; Substance Withdrawal Syndrome; Ventral Tegmental Area

Once dependent on alcohol or opioids, negative affect may accompany withdrawal. Dependent individuals are hypothesized to "self-medicate" in order to cope with withdrawal, which promotes escalated alcohol and drug use.. The current study aimed to develop a reliable animal model to assess symptoms that occur during spontaneous alcohol and opioid withdrawal.. Dependence was induced using intermittent alcohol exposure or pulsatile heroin delivery and assessed for the presence of withdrawal symptoms during acute withdrawal by measuring somatic signs, behavior in the forced swim test (FST), and air-puff-induced 22-kHz ultrasonic vocalizations (USVs). Additional animals subjected to 8 weeks of alcohol vapor exposure were evaluated for altered somatic signs, operant alcohol self-administration, and 22-kHz USV production, as well as performance in the elevated plus maze (EPM).. During spontaneous withdrawal from pulsatile heroin or intermittent alcohol vapor, animals displayed increased somatic withdrawal signs, FST immobility, and 22-kHz USV production but did not show any behavioral change in the EPM unless the duration of alcohol exposure was extended to 4 weeks. Following 8 weeks of alcohol vapor exposure, animals displayed somatic withdrawal signs, escalated alcohol self-administration, and increased 22-kHz USVs.. These paradigms provide consistent methods to evaluate the behavioral ramifications, and neurobiological substrates, of alcohol and opioid dependence during spontaneous withdrawal. As immobility in the FST and percent open-arm time in the EPM were dissociable, with 22-kHz USVs paralleling immobility in the FST, assessment of air-puff-induced 22-kHz USVs could provide an ethologically valid alternative to the FST.

Topics: Affect; Alcoholism; Animals; Conditioning, Operant; Disease Models, Animal; Ethanol; Heroin; Heroin Dependence; Male; Maze Learning; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome; Swimming; Time Factors; Vocalization, Animal

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

To investigate and compare the integrity of white matter in heroin-addicted and healthy control subjects at different abstinent time using diffusion tensor imaging.. We performed voxelwise analysis of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in 35 currently abstinent heroin abusers who were divided into long-term group (n = 17) and short-term group (n = 18) and 17 healthy volunteers. Measurements of FA and ADC of the identified regions (genu and splenium of corpus callosum, bilateral frontal lobe) were obtained from all subjects.. The FA at callosal splenium was higher in the long-term group than in the short-term group (P < 0.05). The FA at left prefrontal cortex was higher in the short-term group than in the long-term group (P < 0.05). No significant difference in ADC was found among the 3 groups. The education history had a positive correlation with the FA value on the gena of corpus callosum (r = 0.402, P = 0.017). Months of abstinence had a negative correlation with left frontal FA (r = -0.366, P = 0.03) and a positive correlation with splenium FA (r = 0.348, P = 0.04).. Heroin abuse seems to alter white matter microstructure differentially in long-term and short-term heroin addicts. This study will contribute to the current literature by examining the quality of white matter fiber structure in heroin abstinence.

Topics: Adult; Aged; Brain; Corpus Callosum; Diffusion Magnetic Resonance Imaging; Female; Follow-Up Studies; Frontal Lobe; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Male; Middle Aged; Substance Withdrawal Syndrome; Young Adult

To investigate the effects of purine nucleotide on the expressions of follicle-stimulating hormone (FSH) and luteotrophic hormone (LH) and the ultrastructures of the distal somatotrophic and gonadotrophic cells in the pituitary gland of heroin-addicted and -withdrawal rats.. Ninety-two male Wistar rats were randomly divided into a control group (ip saline for 14 d), a nucleotide group (ip AMP and GMP for 10 d), a heroin group (ip heroin for 10 d), a heroin + nucleotide group (ip AMP and GMP + heroin for 10 d), a 3 d withdrawal group (ip heroin for 10 d and killed at 14 d), a 9 d withdrawal group (ip heroin for 10 d and killed at 20 d), a 3 d nucleotide group (ip nucleotide for 3 d after 10 d heroin administration and killed at 14 d), and a 9 d nucleotide group (ip nucleotide for 9 d after 10 d heroin administration and killed at 20 d). Changes in the mRNA expressions of FSH and LH in the pituitary gland of the rats were analyzed by semi-quantitative RT-PCR, and alterations in the ultrastructures of the distal somatotrophic and gonadotrophic cells were observed under the microscope.. The expression of FSH mRNA was significantly increased in the nucleotide, heroin + nucleotide, 3 d nucleotide and 9 d nucleotide groups (0.099 +/- 0.018, 0.177 +/- 0.046, 0.151 +/- 0.030 and 0.184 +/- 0.028) as compared with the control group (0.045 +/- 0.009) (P < 0.01); and so was that of LH mRNA in the heroin + nucleotide, 3 d nucleotide and 9 d nucleotide groups (0.950 +/- 0.169, 0.990 +/- 0.171 and 0.960 +/- 0.147) in comparison with the control group (0.700 +/- 0.099) (P < 0.01). In the heroin group, the nuclei of the distal somatotrophic and gonadotrophic cells exhibited morphological abnormality, unclear membrane, slightly pyknotic matrix, marginal and agglutinated heterochromatin, dilated rough endoplasmic reticula, swollen mitochondria, broken and vacuolated cristae in the cytoplasm, obviously decreased number of secretory granules, and myelin bodies in some cells. However, the heroin + nucleotide group showed no significant changes in the ultrastructures of somatotrophic and gonadotrophic cells compared with the control group.. Short-term use of heroin does not obviously affect the expressions of FSH and LH mRNA in the pituitary gland of rats, while heroin + nucleotide, or nucleotide following heroin withdrawal can enhance their expressions significantly. Heroin damages the ultrastructures of the distal somatotrophic and gonadotrophic cells in the pituitary gland of male rats, and purine nucleotide can diminish or inhibit this damage.

Topics: Animals; Follicle Stimulating Hormone; Gene Expression; Heroin; Heroin Dependence; Luteinizing Hormone; Male; Pituitary Gland; Purine Nucleotides; Rats; Rats, Wistar; Substance Withdrawal Syndrome

Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving.. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed.. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P < 0.01, and r = -0.36, P < 0.01, respectively) and after controlling for the effects of potential confounders (β = -0.38, P < 0.01, and β = -0.42, P < 0.01, respectively).. Cholesterol could be associated with the cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

Topics: Adult; Body Mass Index; Cholesterol; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Motivation; Narcotics; Opiate Substitution Treatment; Recurrence; Risk Factors; Statistics as Topic; Substance Withdrawal Syndrome; Surveys and Questionnaires

The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems.

Topics: Animals; Antioxidants; Ceruloplasmin; Glutathione; Heroin; Heroin Dependence; Lipid Peroxidation; Male; Malondialdehyde; Melatonin; Naloxone; Nitrates; Nitrites; Oxidative Stress; Rats; Rats, Sprague-Dawley; Selenium; Substance Withdrawal Syndrome; Vitamin E

Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were paired with a tone-light cue) and tested for cue-induced heroin-seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time-dependent increases in extinction responding were associated with time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens. Additionally, acute accumbens (but not VTA) GDNF injections (12.5 µg/side) administered 1-3 hours after the last heroin self-administration training session enhanced the time-dependent increases in extinction responding after withdrawal. However, the time-dependent increases in extinction responding after withdrawal were not associated with changes in GDNF protein expression in VTA and accumbens. Additionally, interfering with endogenous GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies (600 ng/side/day) into VTA or accumbens had no effect on the time-dependent increases in extinction responding. In summary, heroin self-administration and withdrawal regulate VTA and accumbens GDNF mRNA expression in a time-dependent manner, and exogenous GDNF administration into accumbens but not VTA potentiates cue-induced heroin seeking. However, based on the GDNF protein expression and the anti-GDNF monoclonal neutralizing antibodies manipulation data, we conclude that neither accumbens nor VTA endogenous GDNF mediates the incubation of heroin craving.

Topics: Animals; Association Learning; Cues; Extinction, Psychological; Glial Cell Line-Derived Neurotrophic Factor; Heroin; Heroin Dependence; Male; Narcotics; Nucleus Accumbens; Rats; Rats, Long-Evans; RNA, Messenger; Substance Withdrawal Syndrome; Ventral Tegmental Area

In a rat model of context-induced relapse to heroin, we identified sparsely distributed ventral medial prefrontal cortex (mPFC) neurons that were activated by the heroin-associated context. Selective pharmacogenetic inactivation of these neurons inhibited context-induced drug relapse. A small subset of ventral mPFC neurons formed neuronal ensembles that encode the learned associations between heroin reward and heroin-associated contexts; re-activation of these neuronal ensembles by drug-associated contexts during abstinence provoked drug relapse.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Heroin; Heroin Dependence; Nerve Net; Neurons; Prefrontal Cortex; Rats; Secondary Prevention; Substance Withdrawal Syndrome

The prevalence of opioid abuse and dependence has been on the rise in just the past few years. Animal studies indicate that extended access to heroin produces escalation of intake over time, whereas stable intake is observed under limited-access conditions. Escalation of drug intake has been suggested to model the transition from controlled drug use to compulsive drug seeking and taking. Here, we directly compared the pattern of heroin intake in animals with varying periods of heroin access. Food intake was also monitored over the course of escalation. Rats were allowed to lever press on a fixed-ratio 1 schedule of reinforcement to receive intravenous infusions of heroin for 1, 6, 12, or 23h per day for 14 sessions. The results showed that heroin intake in the 12 and 23h groups markedly increased over time, whereas heroin intake in the 1h group was stable. The 6h group showed a significant but modest escalation of intake. Total heroin intake was similar in the 12 and 23h groups, but the rate of heroin self-administration was two-fold higher in the 12h group compared with the 23h group. Food intake decreased over sessions only in the 12h group. The 12 and 23h groups showed marked physical signs of naloxone-precipitated withdrawal. These findings suggest that 12h heroin access per day may be the optimal access time for producing escalation of heroin intake. The advantages of this model and the potential relevance for studying drug addiction are discussed.

Topics: Animals; Behavior, Animal; Disease Models, Animal; Drug-Seeking Behavior; Heroin; Heroin Dependence; Humans; Male; Naloxone; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome; Time Factors

Research on heroin withdrawal has primarily been done clinically, thus focussing on symptom severity, physiological manifestations, and how withdrawal impairs normal functioning. However, there is little scientific knowledge on how heroin withdrawal affects injection behaviour. This paper explores how withdrawal episodes heighten unsafe injection practices and how some long-term injectors manage such risks.. We interviewed 32 injection drug users in New York City who had been injecting drugs for 8-15 years (21 HIV and HCV uninfected; 3 HIV and HCV infected; and 8 singly infected with HCV). We used in-depth life history interviews to inquire about IDUs' life history, injection practices and drug use behaviour over time. Analysis used grounded theory techniques.. Withdrawal can enhance risk by undermining IDUs' willingness to inject safely; increasing the likelihood of attending risky settings; raising the number of injection partners; and seeking ad hoc partners for drug or needle sharing. Some IDUs have developed practices to cope with withdrawal and avoid risky practices (examples include carrying clean needles to shooting galleries and sniffing rather than injecting). Strategies to avoid withdrawal include back up methods, resorting to credit, collaborating with others, regimenting drug intake, balancing drug intake with money available, and/or resorting to treatment.. Withdrawal periods can heighten risky injection practices. Some IDUs have applied strategies to avoid withdrawal or used practices to cope without engaging in risky practices. These behaviours might in turn help IDUs prevent an infection with hepatitis C or HIV.

Topics: Adaptation, Psychological; Health Knowledge, Attitudes, Practice; Hepatitis C; Heroin; HIV Infections; Humans; Risk Factors; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

The neural and psychological mechanisms underlying vulnerability to drug addiction are poorly understood. Although a number of animal models have been developed to investigate vulnerability to stimulant addiction, few have considered how vulnerability traits such as impulsivity predict hallmark features of heroin addiction including the escalation of drug intake and increased propensity for relapse following protracted abstinence.. The aim of this study was to investigate whether high impulsivity in rats predicts the propensity to escalate intravenous heroin self-administration and to relapse following an extended withdrawal period from heroin.. High (HI)- and low (LI)-impulsive rats, defined by the extent of premature responding on the 5-choice serial reaction time test (5-CSRTT), were catheterized and allowed to self-administer heroin (40 μg/100 μl/infusion). After 5 days of short access (1 h/day) to heroin, rats were then given extended (6 h/day) access to heroin for 18 consecutive days.. High impulsivity predicted neither a greater tendency to acquire heroin SA nor an increased escalation of heroin self-administration. Moreover, high impulsivity was not associated with an increased propensity to relapse after protracted withdrawal from heroin. Nevertheless, marked inter-individual differences in the escalation of heroin self-administration were observed.. Although high impulsivity on the 5-CSRTT has been shown to predict loss of control over cocaine intake, this does not generalize to a loss of control over heroin self-administration. These findings suggest important distinctions in vulnerability mechanisms underlying cocaine and heroin addiction with trait-like impulsivity playing a role in stimulant but not opiate addiction.

Topics: Analgesics, Opioid; Animals; Attention; Behavior, Addictive; Behavior, Animal; Conditioning, Operant; Cues; Extinction, Psychological; Heroin; Heroin Dependence; Infusions, Intravenous; Male; Rats; Recurrence; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome; Time Factors

Opioid withdrawal can produce a constellation of physiological and behavioral signs, including an increase in opioid self-administration. Different mechanisms mediate different withdrawal signs, and the present study used pharmacologic tools to assess mechanisms underlying withdrawal-associated increases in opioid reinforcement. Five rhesus monkeys were rendered heroin dependent via daily 21-h heroin self-administration sessions. One hour after each heroin self-administration session, monkeys chose between heroin (0-0.1 mg/kg per injection) and food (1 g pellets) during 2-h choice sessions. Under these conditions, heroin maintained a dose-dependent increase in heroin choice, such that monkeys responded primarily for food when low heroin doses were available (0-0.01 mg/kg per injection) and primarily for heroin when higher heroin doses were available (0.032-0.1 mg/kg per injection). Periods of spontaneous withdrawal were intermittently introduced by omitting one 21-h heroin self-administration session, and test drugs were administered during these withdrawal periods. Untreated withdrawal robustly increased heroin choice during choice sessions. Withdrawal-associated increases in heroin choice were completely suppressed by the mu opioid agonist morphine (0.032-0.32 mg/kg/h, i.v.), but not by the alpha-2 noradrenergic agonist clonidine (0.01-0.1 mg/kg/h, i.v.), the dopamine/norepinephrine releaser amphetamine (0.032-0.1 mg/kg/h, i.v.), or the kappa-opioid antagonist 5'-guanidinonaltrindole (1.0 mg/kg, i.m.). The corticotropin-releasing factor 1 antagonist antalarmin (1.0-10 mg/kg per day, i.m.) produced a morphine-like suppression of withdrawal-associated increases in heroin choice in one of three monkeys. These results suggest that mechanisms of withdrawal-associated increases in the relative reinforcing efficacy of opioid agonists may be different from mechanisms of many other somatic, mood-related, and motivational signs of opioid withdrawal.

Topics: Adrenergic Agents; Adrenergic Agonists; Amphetamine; Animals; Behavior, Addictive; Choice Behavior; Clonidine; Dopamine Agents; Dose-Response Relationship, Drug; Food; Heroin; Heroin Dependence; Macaca mulatta; Male; Morphine; Narcotic Antagonists; Pyrimidines; Pyrroles; Receptors, Corticotropin-Releasing Hormone; Self Administration; Substance Withdrawal Syndrome

Topics: Adult; Analgesics, Opioid; Aorta; Blood Pressure; Buprenorphine; Female; Hemodynamics; Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

A high incidence of relapse can be triggered by exposure to conditioned cues previously associated with heroin. Extended access to drug and withdrawal are thought to affect the motivation for drug seeking.. The present study evaluated how different periods of training to self-administer heroin and different periods of withdrawal affected drug seeking.. Following 1 to 14 days of heroin self-administration, rats were left in the home environment for 1 or 14 days. Subsequently, rats were evaluated for extinction of nose poke during the first hour after being returned to the training apparatus. One hour later, a conditioned stimulus was presented to initiate cue-induced reinstatement.. Extending the training period from 1 to 14 days caused an escalation of reinstatement of drug seeking induced by conditioned cues. Increasing the withdrawal period from 1 to 14 days produced a similar increase in reinstatement of drug seeking induced by cues. Reinstatement of drug seeking induced by cues was augmented by pretreatment with naltrexone (1, 5 mg/kg) 24 h prior to reinstatement on day 1, but not at 14 days of withdrawal from heroin self-administration.. These experiments demonstrate that increasing the duration of either heroin self-administration or the withdrawal periods from heroin self-administration augments the reinstatement induced by cues that were associated previously with heroin reinforcement. Additionally, we provide one of the first demonstrations that opiate withdrawal induces heroin seeking, as assessed in the reinstatement model.

Topics: Animals; Behavior, Addictive; Behavior, Animal; Conditioning, Operant; Cues; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Exploratory Behavior; Heroin; Heroin Dependence; Male; Naltrexone; Narcotic Antagonists; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Secondary Prevention; Self Administration; Substance Withdrawal Syndrome

The study evaluated the adulterants in a specimen of illicit street heroin supplied under strict control by the Pakistan Anti-Narcotic Force. It also examined the effects of Hypericum perforatum L. extracts on the naloxone-induced heroin withdrawal syndrome. The GC-MS analysis of the specimen showed that in addition to heroin (37.8%), the sample also contained caffeine (8.4%), phenobarbitone (12.7%), 6-acetyl codeine (5.3%), 6-acetyl morphine (10.9%) and noscapine (15.8%). Administration of the heroin to rats for 8 days induced physical withdrawal signs of abdominal constriction, diarrhoea and vocalization on touch after naloxone treatment. Aqueous Hypericum perforatum extracts (20 mg/kg twice daily chronically or as a single acute dose 90 min before naloxone) given orally to the heroin dependent rats attenuated abdominal constrictions both acutely and chronically while the hydroethanol and ethanol extracts were only effective in acutely treated animals. Diarrhoea was ameliorated by the hydroethanol and ethanol extracts following acute or chronic heroin treatment while the aqueous extract failed to show any effect. Vocalization on touch during withdrawal was reduced by all the extracts either chronically or acutely with the exception of chronic treatment with hydroethanol extracts. The findings suggest that Hypericum perforatum is capable of reducing the physical signs of opiate withdrawal.

Topics: Animals; Diarrhea; Gas Chromatography-Mass Spectrometry; Heroin; Hypericum; Naloxone; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome; Vocalization, Animal

Dependence can develop during chronic opioid use, and the emergence of withdrawal might promote drug taking.. This study examined how chronic morphine administration or withdrawal modified self administration of heroin or cocaine.. Four monkeys responded under a fixed ratio 10 schedule to receive i.v. infusions of heroin (0.56-560 microg/kg/infusion) or cocaine (1-100 microg/kg/infusion). Monkeys received morphine twice daily; the final dose was 10 mg/kg/12 h. Dose-effect curves for heroin or cocaine were determined in 150-min sessions throughout morphine administration and during temporary suspension when withdrawal signs were also monitored. Heroin dose-effect curves and withdrawal signs were determined daily following termination of morphine administration.. Before monkeys received morphine, heroin, and cocaine maintained responding with unit doses of 1.78 microg/kg of heroin and 10 microg/kg/injection of cocaine resulting in, on average, 13.4 and 20.8 infusions, respectively. When monkeys received morphine daily, self administration of heroin and cocaine decreased to, on average, 3.1 and 11.3 infusions, respectively. Responding for heroin or cocaine recovered following temporary (17-53 h) suspension of morphine administration. The number of heroin infusions and total withdrawal signs increased when morphine administration was terminated. Withdrawal signs peaked 3-4 days after morphine; however, the number of infusions remained elevated for 8 weeks.. Changes in self administration responding did not precisely covary with signs of withdrawal and responding for small doses of heroin persisted long after discontinuation of morphine, suggesting that non-pharmacologic (e.g., conditioned reinforcing) effects might contribute to the maintenance of lever pressing under these conditions.

Topics: Animals; Cocaine; Conditioning, Operant; Dose-Response Relationship, Drug; Female; Heroin; Macaca mulatta; Male; Morphine Dependence; Narcotics; Reinforcement Schedule; Self Administration; Substance Withdrawal Syndrome

The aim of the present study was to investigate the changes in the pituitary-thyroid axis (PTA) and the time course of the hormonal alterations in subjects with opioid dependence after abstinence. Blood samples from in-patients with opioid dependence and age- and sex-matched healthy controls were collected. The severity of opioid abuse and of withdrawal symptoms was assessed. Results were compared between patients with opioid dependence (n = 30) and healthy controls (n = 30). We found that free triiodothyronine and free thyroxine levels were comparable with healthy controls while thyroid-stimulating hormone (TSH) was lower in patients in acute opioid abstinence period. Also, TSH levels in patients remained lower than controls after 30 days of abstinence. These results indicate that PTA function is altered in opioid-dependent subjects. These data highlight the importance of screening the thyroid function for individuals with chronic opioid dependence.

Topics: Adult; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Male; Narcotics; Pituitary Gland, Anterior; Reference Values; Substance Withdrawal Syndrome; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

The juxtacapsular bed nucleus of the stria terminalis (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of the amygdala. Here we show a form of long-term potentiation of the intrinsic excitability (LTP-IE) of jcBNST neurons in response to high-frequency stimulation of the stria terminalis. This LTP-IE, which was characterized by a decrease in the firing threshold and increased temporal fidelity of firing, was impaired during protracted withdrawal from self-administration of alcohol, cocaine, and heroin. Such impairment was graded and was more pronounced in rats that self-administered amounts of the drugs sufficient to maintain dependence. Dysregulation of the corticotropin-releasing factor (CRF) system has been implicated in manifestation of protracted withdrawal from dependent drug use. Administration of the selective corticotropin-releasing factor receptor 1 (CRF(1)) antagonist R121919 [2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine)], but not of the CRF(2) antagonist astressin(2)-B, normalized jcBNST LTP-IE in animals with a history of alcohol dependence; repeated, but not acute, administration of CRF itself produced a decreased jcBNST LTP-IE. Thus, changes in the intrinsic properties of jcBNST neurons mediated by chronic activation of the CRF system may contribute to the persistent emotional dysregulation associated with protracted withdrawal.

Topics: Animals; Cocaine; Ethanol; Heroin; Long-Term Potentiation; Rats; Rats, Wistar; Self Administration; Septal Nuclei; Substance Withdrawal Syndrome

Although morphine and heroin analgesia is mediated by mu-opioid receptors encoded by the MOR-1 gene, distinct isoforms are involved. Both opioids also induce dependence by acting at mu-opioid receptors, but which variants are utilized is not known. Here, we assayed morphine and heroin analgesia and dependence in mice treated with antisense oligodeoxynucleotides (AO) targeting MOR-1 exons 1-4. Whereas AOs targeting exons 1 and 4 blocked morphine analgesia, those targeting exons 2 and 3 blocked heroin analgesia. Neither morphine nor heroin analgesia was compromised 5 days after the last AO injection. In morphine and heroin dependent mice, only exon 1 AO significantly reduced jumping incidence during naloxone (50mg/kg) precipitated withdrawal. Neither analgesia nor withdrawal jumping was attenuated in controls pretreated with saline or a mismatch oligodeoxynucleotide control sequence. While these data confirm previous reports that morphine and heroin analgesia are not mediated by a single mu-opioid receptor, both opiates nonetheless apparently induce dependence via a mu-opioid receptor isoform containing exon 1. For heroin, the possibility that analgesia and dependence are mediated by distinct mu-opioid receptor isoforms offers the prospect of developing potent opiate analgesics possessing reduced dependence liability.

Topics: Analgesia; Analgesics, Opioid; Analysis of Variance; Animals; Exons; Heroin; Heroin Dependence; Hot Temperature; Male; Mice; Morphine; Morphine Dependence; Motor Activity; Naloxone; Narcotic Antagonists; Oligonucleotides, Antisense; Pain Measurement; Protein Isoforms; Receptors, Opioid, mu; Substance Withdrawal Syndrome

Heroin use and withdrawal cause abnormality in the endocrine system. However, the time course of neuroendocrine alterations in heroin addicts during pharmacologically unassisted withdrawal is still unclear.. To investigate alterations in cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), leptin, and neuropeptide Y (NPY) during the first month of abstinence in heroin addicts.. Twelve heroin addicts and eight matched healthy control subjects were recruited for this study. The neuroendocrine alterations and self-reported heroin craving, anxiety, and depression in heroin addicts were assessed at different time points (days 3, 10, and 30) of first month of abstinence from heroin use.. Self-reported heroin craving, anxiety, and depression in heroin addicts decreased gradually during the first month of abstinence. The cortisol levels increased from abstinence day 3 to 30, while ACTH and beta-EP levels decreased over this period in heroin addicts. The leptin and NPY levels were significantly decreased on days 3 and 10 but had normalized on day 30 of abstinence. A positive correlation between cortisol level and heroin craving, anxiety, and depression was observed, while a negative correlation was observed between beta-EP level and craving and anxiety and between leptin and depression and NPY and anxiety.. Abnormal alterations in the neuroendocrine system, including levels of cortisol, ACTH and beta-EP persist throughout the first month of abstinence. These results suggest that neuroendocrine system dysfunctions in heroin abusers is independent of the acute and protracted withdrawal syndromes, and may thus contribute to relapse to heroin use.

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; Anxiety; beta-Endorphin; Case-Control Studies; Depression; Heroin; Heroin Dependence; Humans; Hydrocortisone; Leptin; Male; Neuropeptide Y; Neurosecretory Systems; Patient Selection; Psychiatric Status Rating Scales; Radioimmunoassay; Substance Withdrawal Syndrome; Time Factors

A previous study has shown that the stress responsive neurohormone arginine vasopressin (AVP) is activated in the amygdala during early withdrawal from cocaine. The present studies were undertaken to determine whether (1) AVP mRNA levels in the amygdala or hypothalamus, as well as hypothalamic-pituitary-adrenal (HPA) activity, would be altered during chronic intermittent escalating heroin administration (10 days; 7.5-60 mg/kg/day) or during early (12 h) and late (10 days) spontaneous withdrawal; (2) foot shock stress would alter AVP mRNA levels in the amygdala or hypothalamus in rats withdrawn from heroin self-administration (7 days, 3 h/day, 0.05 mg/kg/infusion); and (3) the selective V1b receptor antagonist SSR149415 (1 and 30 mg/kg, intraperitoneal) would alter heroin seeking during tests of reinstatement induced by foot shock stress and by heroin primes (0.25 mg/kg), as well as HPA hormonal responses to foot shock. We found that AVP mRNA levels were increased during early spontaneous withdrawal in the amygdala only. This amygdalar AVP mRNA increase was no longer observed at the later stage of heroin withdrawal. Foot shock stress increased AVP mRNA levels in the amygdala of rats withdrawn from heroin self-administration, but not in heroin naïve rats. Behaviorally, SSR149415 dose-dependently attenuated foot shock-induced reinstatement and blocked heroin-induced reinstatement. Finally, SSR149415 blunted the HPA activation by foot shock. Together, these data in rats suggest that stress responsive AVP/V1b receptor systems (including the amygdala) may be critical components of the neural circuitry underlying the aversive emotional consequences of drug withdrawal, as well as the effect of negative emotional states on drug-seeking behavior.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Corticosterone; Exploratory Behavior; Heroin; Heroin Dependence; Male; Rats; Rats, Inbred F344; Receptors, Vasopressin; RNA, Messenger; Substance Withdrawal Syndrome

Although the repercussion of chronic treatment with large amounts of opioids on cognitive performance is a matter of concern, the effects of opioid drugs on passive avoidance learning have been scarcely studied. Here, we analyzed the effects of prolonged administration of heroin and methadone, as well as the impact of suffering repeated episodes of withdrawal on fear-motivated learning using the passive avoidance test. Mice received chronic treatment (39 days) with methadone (10 mg/kg/24 h), associated or not with repeated withdrawal episodes, or with heroin (5 mg/kg/12 h). Our results show that, regardless of the type of treatment received, all mice displayed similar basal thermal nociceptive thresholds during 25 days of treatment. In the hot plate test, both methadone and heroin induced antinociception 30 min after drug administration. The analgesic effect was absent when measured 4 h after heroin and 12 h after methadone. Pain behavioural responses elicited by growing intensities of electric shock, applied on day 28th of treatment, were similar in all groups of mice. Our results indicate that chronic opioid treatment had promnesic effects on passive avoidance behaviour in mice, unrelated to changes in the nociceptive state.

Topics: Analysis of Variance; Animals; Avoidance Learning; Behavior, Animal; Drug Administration Schedule; Fear; Heroin; Male; Methadone; Mice; Mice, Inbred C57BL; Narcotics; Sensory Thresholds; Statistics, Nonparametric; Substance Withdrawal Syndrome; Time Factors

In the accompanying paper, we described incubation of heroin-seeking behavior in rats following 14 days of abstinence. To gain an understanding of genomic changes that accompany this behavioral observation, we measured the expression of genes previously reported to respond to drugs of abuse. Specifically, after 1 or 14 days of abstinence, mRNA expression was measured for 11 genes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) immediately following a single 90 min extinction session. Additionally, the role of contingency was examined in control rats that received yoked, response-independent heroin administration. Gene expression was quantified by real-time quantitative PCR. Expression of five genes (Arc, EGR1, EGR2, Fos, and Homer1b/c) was changed in the mPFC. EGR1 and EGR2 expression was increased following the 90 min extinction session in a contingency-specific manner and this increase persisted through the 14 days of abstinence. Fos expression was also increased after 1 and 14 days of abstinence, but at 14 days this increase was response-independent (i.e., it occurred in both the rats with a history of heroin self-administration and in the yoked controls). Arc expression increased following the extinction session only in rats with a history of heroin self-administration and only when tested following 1, but not 14, days of abstinence. Homer 1 b/c decreased after 14 days of enforced abstinence in rats that received non-contingent heroin. Expression of only a single gene (EGR2) was increased in the NAc. These data demonstrate that behavioral incubation is coincident with altered levels of specific transcripts and that this response is contingently-specific. Moreover, EGR1 and EGR2 are specifically upregulated in self-administering rats following extinction and this finding persists through 14 days of abstinence, suggesting that these genes are particularly associated with the incubation phenomenon. These latter observations of persistent changes in gene expression following abstinence may reflect molecular correlates of relapse liability.

Topics: Animals; Behavior, Animal; Body Weight; Central Nervous System; Cues; Drinking; Extinction, Psychological; Gene Expression; Heroin; Heroin Dependence; Male; Narcotics; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA; Substance Withdrawal Syndrome

Opioid receptor agonists can enhance some effects of cannabinoid receptor agonists, and cannabinoid receptor agonists can enhance some effects of opioid receptor agonists; however, the generality of these interactions is not established.. This study examined interactions between the discriminative stimulus and antinociceptive effects of mu opioid receptor agonists and Delta(9)-tetrahydrocannabinol (THC) in rhesus monkeys.. Neither heroin nor morphine (intravenous (i.v.) or subcutaneous (s.c.)) altered the discriminative stimulus effects of THC in monkeys (n = 5) discriminating 0.1 mg/kg THC i.v. In contrast, THC (s.c.) markedly attenuated the discriminative stimulus effect of morphine and heroin in nondependent monkeys (n = 4) discriminating 1.78 mg/kg morphine s.c. Doses of THC that attenuated the discriminative stimulus effects of morphine in nondependent monkeys failed to modify the discriminative stimulus effects of morphine in morphine-dependent (5.6 mg/kg/12 h) monkeys (n = 4) discriminating 0.0178 mg/kg naltrexone s.c. THC also failed to modify the discriminative stimulus effects of naltrexone in morphine-dependent monkeys or the effects of midazolam in monkeys (n = 4) discriminating 0.32 mg/kg midazolam s.c. Doses of THC (s.c.) that attenuated the discriminative stimulus effects of morphine in nondependent monkeys enhanced the antinociceptive effects of morphine (s.c.) in nondependent monkeys. While mu receptor agonists did not alter the discriminative stimulus effects of THC, THC altered the effects of mu receptor agonists in a context-dependent manner.. That the same doses of THC enhance, attenuate, or do not affect morphine, depending on the condition, suggests that attenuation of morphine by THC can result from perceptual masking rather than common pharmacodynamic mechanisms or pharmacokinetic interactions.

Topics: Analgesics; Analgesics, Opioid; Animals; Data Interpretation, Statistical; Discrimination, Psychological; Dose-Response Relationship, Drug; Dronabinol; Drug Interactions; Female; Heroin; Hot Temperature; Hypnotics and Sedatives; Macaca mulatta; Male; Midazolam; Morphine; Morphine Dependence; Naltrexone; Narcotic Antagonists; Pain Measurement; Receptors, Opioid, mu; Substance Withdrawal Syndrome

This study used heroin self-administration to investigate incubation of goal-directed heroin-seeking behavior following abstinence. Male Sprague-Dawley rats self-administered heroin on a fixed ratio 10 (FR10) schedule of reinforcement with licking of an empty spout serving as the operant behavior during 14 daily 3 h sessions. After this acquisition period, all rats received a 90 min extinction session following either 1 day or 14 days of home cage abstinence. When the extinction session occurred after only 1 day of home cage abstinence, rats with a history of heroin self-administration divided their responses equally between the previously "active" and "inactive" spouts. However, when the extinction session occurred following 14 days of home cage abstinence, the rats exhibited marked goal-directed heroin-seeking behavior by licking more on the previously "active" than "inactive" spout. These findings demonstrate that heroin-seeking behavior incubates over time, resulting in goal-directed heroin-seeking behavior in rats following 14 days but not 1 day of abstinence. Moreover, this facilitatory effect occurred in response to a different training schedule, lower total drug intake, and shorter periods of daily access than previously reported with heroin.

Topics: Animals; Conditioning, Operant; Extinction, Psychological; Goals; Heroin; Heroin Dependence; Male; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Self Administration; Substance Withdrawal Syndrome; Water Deprivation

Buprenorphine has been approved for heroin detoxification, but little is known about its impact on everyday practice. Concerns about buprenorphine include expense, limited knowledge about its use, patient limits, and social and clinical attitudes regarding opioid treatment for heroin dependence. On the other hand, randomized clinical trials suggest that buprenorphine is superior to clonidine with regard to withdrawal symptom relief. In June 2004, a community-based residential medical detoxification center switched from clonidine to buprenorphine treatment for all new and returning heroin clients. This study is a retrospective chart review of subject outcomes with clonidine (n = 100) versus buprenorphine (n = 100). Bivariate analysis suggested few cohort differences in pretreatment demographics and client characteristics. In contrast, buprenorphine was significantly associated with increased length of stay and treatment completion. The positive associations between buprenorphine and both treatment completion and length of stay persisted and were slightly enhanced after regression analysis adjusted for potential confounders. Additionally, clinical staff reported better subject engagement in treatment and psychosocial group sessions. This single-site study is an example of successful integration of an evidence-based treatment into community-based practice.

Topics: Acute Disease; Adult; Buprenorphine; Clonidine; Diffusion of Innovation; Female; Heroin; Heroin Dependence; Humans; Length of Stay; Male; Middle Aged; Narcotics; Oregon; Patient Acceptance of Health Care; Retrospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

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

Opioid overdose, which is commonly associated with opioid induced respiratory depression, is a problem with both therapeutic and illicit opioid use. While the central mechanisms involved in the effects of opioids are well described, it has also been suggested that a peripheral component may contribute to the effects observed. This study aimed to further characterise the effects of the peripherally acting naloxone methiodide on the respiratory, analgesic and withdrawal effects produced by various opioid agonists. A comparison of the respiratory and analgesic effects of morphine, methadone and heroin in male Swiss-Albino mice was conducted and respiratory depressive ED(80) doses of each opioid determined. These doses (morphine 9 mg/kg i.p., methadone 7 mg/kg i.p., and heroin 17 mg/kg i.p.) were then used to show that both naloxone (3 mg/kg i.p.) and naloxone methiodide (30-100 mg/kg i.p.) could reverse the respiratory and analgesic effects of these opioid agonists, but only naloxone precipitated withdrawal. Further investigation in female C57BL/6J mice using barometric plethysmography found that both opioid antagonists could reverse methadone induced decreases in respiratory rate and increases in tidal volume. Its effects do not appear to be strain or sex dependent. It was concluded that naloxone methiodide can reverse the respiratory and analgesic actions of a variety of opioid agonists, without inducing opioid withdrawal.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Drug Interactions; Female; Heroin; Male; Methadone; Mice; Mice, Inbred C57BL; Morphine; Naloxone; Plethysmography, Whole Body; Quaternary Ammonium Compounds; Respiration; Respiratory Insufficiency; Substance Withdrawal Syndrome

To investigate the effect of heroin on purine nucleotides catabolism, a rat model of heroin administration and withdrawal was established. Concentrations of uric acid, creatinine, and urea nitrogen in plasma and ADA in plasma, brain, liver, and small intestine were tested. When two heroin administration groups were compared with the control group, the concentrations of plasma uric acid and ADA in plasma, brain, liver, and small intestine increased, whereas the plasma urea nitrogen concentrations in two heroin administration groups and the plasma creatinine concentration in the 3-day heroin administration group did not increase. It seemed that heroin exposure for a short time did not affect renal clearance rate notably. When two withdrawal groups were compared with two heroin administration groups, the concentrations of plasma uric acid and ADA in liver and small intestine decreased, but there was no significant reduction in ADA concentrations of the brain, while the plasma ADA concentrations in the two withdrawal groups were significantly higher than those of two heroin administration groups. When the two withdrawal groups were compared with the control group, there was no significant difference in the concentrations of plasma uric acid and ADA in liver and small intestine, while the concentrations of ADA in plasma and brain were still higher than those of the control group. The results imply that heroin administration may enhance the catabolism of purine nucleotides in the brain and other tissues by increased concentration of ADA and the effect may last for a long time in the brain.

Topics: Adenosine Deaminase; Animals; Brain; Disease Models, Animal; Heroin; Heroin Dependence; Male; Purine Nucleotides; Rats; Rats, Wistar; Substance Withdrawal Syndrome; Urea; Uric Acid

The prevalence of cocaine use in opioid-dependent individuals is reportedly high, and the associated negative health and social consequences are severe and well documented. Sensitization of the reinforcing effects of cocaine has been demonstrated following noncontingent opioid exposure in animals; however, no preclinical studies have investigated the impact of opioid self-administration on cocaine's reinforcing effects.. Experiments were designed to investigate whether access to heroin self-administration altered the subsequent reinforcing effects of cocaine.. Baseline responding for cocaine under a progressive ratio schedule was first established. Heroin was then self-administered under a 24-h discrete-trials procedure (DT5; access to heroin five times per hour). Subsequently, cocaine-maintained responding was reassessed.. Here we demonstrate that 10 days of DT5 heroin self-administration (50 microg/kg per infusion) resulted in an increase in cocaine's reinforcing effects at several doses across the cocaine dose-effect curve (0.38-3.0 mg/kg per infusion). These increases were relatively long lasting, exceeding the time course of a mild withdrawal syndrome.. The DT5x10-day history of heroin self-administration resulted in an upward shift in the cocaine dose-effect curve, suggesting that DT5 heroin self-administration produced an increase in potency and sensitization of the maximal effectiveness with which cocaine functions as a reinforcer. The present experiments contribute to a growing amount of preclinical evidence suggesting an impact of opioid exposure on the reinforcing effects of cocaine, which may partially explain the high incidence of cocaine use in opioid-dependent individuals.

Topics: Animals; Cocaine; Dose-Response Relationship, Drug; Heroin; Male; Narcotics; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome

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

Several medications are approved for treatment of opiate abuse, but determinants of their clinical effectiveness are not completely understood. States of opiate dependence or withdrawal may constitute one important set of determinants. To test this hypothesis, the effects of naloxone, buprenorphine, and methadone were assessed on choice between heroin and food in nondependent rhesus monkeys and in heroin-dependent monkeys undergoing withdrawal. A choice procedure was used to permit dissociation of medication effects on the relative reinforcing properties of heroin from nonselective effects on response rates. In nondependent monkeys, increasing unit doses of heroin (0-0.1 mg/kg/injection) maintained dose-dependent increases in heroin choice. Chronic 5-day treatment with naloxone (0.01-0.32 mg/kg/h) or buprenorphine (0.01-0.1 mg/kg/day) produced dose-dependent rightward shifts in heroin choice dose-effect curves, whereas chronic methadone (0.1-0.56 mg/kg/h) had little effect on heroin choice up to doses that suppressed responding. In heroin-dependent monkeys, opiate withdrawal produced overt abstinence signs as well as increases in heroin choice, manifested as leftward shifts in heroin choice dose-effect curves. The withdrawal-associated increases in heroin choice suggest that opiate withdrawal increased the relative reinforcing efficacy of heroin in comparison with food, an effect that may be related to relapse in humans. Methadone prevented withdrawal-associated increases in heroin choice, whereas buprenorphine was less effective. These findings suggest that agonist medications such as methadone may derive their clinical utility from their ability to attenuate withdrawal-associated increases in opiate reinforcement. Moreover, this procedure may be useful for exploring mechanisms underlying withdrawal-associated increases in opiate reinforcement and for testing candidate medications.

Topics: Animals; Buprenorphine; Disease Models, Animal; Feeding Behavior; Heroin; Heroin Dependence; Macaca mulatta; Male; Methadone; Naloxone; Self Administration; Substance Withdrawal Syndrome

The authors investigated the impact of conditioned withdrawal on drug seeking by training rats to work for a heroin infusion on a seeking-taking schedule, which required responding on a seeking lever in order to gain the opportunity to self-administer the drug by a single response on a taking lever. Following the establishment of opiate dependence, a conditioned stimulus (CS) that had been previously paired with naloxone-precipitated withdrawal suppressed heroin seeking in extinction. However, when the rats had prior experience of heroin taking in the presence of the withdrawal CS, drug seeking was elevated in the presence of this stimulus. The authors conclude that the conditioned motivation of drug seeking in withdrawal depends on previous association of the CS with drug taking.

Topics: Animals; Conditioning, Psychological; Food Preferences; Heroin; Male; Motivation; Naltrexone; Narcotic Antagonists; Rats; Substance Withdrawal Syndrome; Sucrose; Time Factors

Aspects of drug withdrawal may become conditioned to previously neutral environmental stimuli via classical conditioning processes. Nevertheless, the significance of conditioned withdrawal effects in motivating drug intake remains largely unexplored. Here, we investigated the effects of conditioned withdrawal in modulating heroin consumption and brain reward sensitivity in rats. Rats intravenously self-administered heroin (20 microg/infusion) during 0 h (control), 1 h (nondependent), or 23 h (dependent) sessions and had daily intracranial self-stimulation (ICSS) thresholds assessed. ICSS thresholds remained stable and unaltered in control rats. In nondependent rats, heroin self-administration induced a transient activation of reward systems, reflected in lowering of ICSS thresholds. In dependent rats, heroin intake escalated across sessions and was associated with a gradual decrease in reward sensitivity, reflected in progressively elevated ICSS thresholds. Thus, as dependence develops, heroin may be consumed not only for its acute reward-facilitating effects, but also to counter persistent deficits in reward sensitivity. In nondependent rats, the opioid receptor antagonist naloxone (30 microg/kg) increased heroin consumption and reversed heroin-induced lowering of ICSS thresholds, effects resistant to classical conditioning. In contrast, in dependent rats naloxone (30 microg/kg) increased heroin consumption and also elevated ICSS thresholds above their already elevated baseline levels (i.e., precipitated withdrawal). Most importantly, stimuli repeatedly paired with naloxone-precipitated withdrawal provoked heroin consumption and elevated ICSS thresholds in dependent rats. Thus, conditioned stimuli predicting the onset of heroin withdrawal, and hence the reward deficits coupled with this state, may play a critical role in provoking craving and relapse in human opiate addicts.

Topics: Animals; Conditioning, Classical; Disease Models, Animal; Electric Stimulation; Heroin; Heroin Dependence; Male; Naloxone; Narcotic Antagonists; Rats; Reward; Self Stimulation; Substance Withdrawal Syndrome

The purpose of this study was the evaluation of clinical heroin symptoms and buprenorphine drug addiction in the withdrawal period with the purpose of their comparison, study of parameters of bone metabolism in the both groups. In the study group were included 40 patients with heroin and 27 with buprenorphine addiction in the period of abstinence. Our investigations have shown, that in the both groups, among clinical symptoms ossalgias, arthralgias and mialgias attributes to the expressed dysfunction of vegetative system, were most prominent. Decrease of sexual functions was found in half of inspected patients. Biochemical investigations have shown intensive clearance of calcium with the urine that indicates intensifying resorbtion processes in the bone tissue. Symptoms of hypogonadism were accompanied by the decrease of the level of testosterone in the blood. Parameters of mineral consistency of the bone tissue was decreased both in patients with heroin and buprenorphine addiction.

Topics: Behavioral Symptoms; Biomarkers; Bone and Bones; Bone Density; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Dependence; Pain; Radiography; Substance Withdrawal Syndrome

Topics: Administration, Inhalation; Asthma; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome

Heroin has been shown to elevate dopamine (DA) level. It is well known that an increase in DA oxidative metabolism leads to increased reactive oxygen species (ROS) formation, and thus, ROS have been frequently associated with neuronal cell death due to damage to carbohydrates, amino acids, phospholipids, and nucleic acids. This study investigated whether there are oxidative stress and effects of exogenous antioxidants in heroin-administered mice. The heroin-dependent mice model was made via intraperitoneal injection. Oxidative damage of DNA, protein, and lipid was measured by analysis of single cell electrophoresis, the 2,4-dinitrophenylhydrazine method, and thiobarbituric acid method respectively. The activities of antioxidative enzymes and total antioxidant capacity were assayed by spectrophotometry. After administration with heroin, the mice not only showed decrease of total antioxidant capacity in serum and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione (GSH) peroxidase in brain, but also exhibited the oxidative damages of DNA, protein and lipid. On the other hand, exogenous antioxidants could restrain the oxidative stress, even alleviate withdrawal syndrome in heroin-administered mice. Our results also imply a possibility that ROS may participate in the whole process of dependence and withdrawal of heroin. Therefore, strategies of blocking oxidative stress may be useful in the development of therapy for opiate abuse.

Topics: Animals; Antioxidants; Brain; Brain Chemistry; Catalase; DNA Damage; Female; Glutathione Peroxidase; Heroin; Heroin Dependence; Injections, Intraperitoneal; Injections, Subcutaneous; Lymphocytes; Male; Malondialdehyde; Mice; Naloxone; Narcotic Antagonists; Narcotics; Oxidative Stress; Substance Withdrawal Syndrome; Superoxide Dismutase

Topics: Animals; Conditioning, Classical; Disease Models, Animal; Electric Stimulation; Heroin; Heroin Dependence; Male; Naloxone; Narcotic Antagonists; Rats; Reward; Self Stimulation; Substance Withdrawal Syndrome

Recent data from our laboratory have demonstrated that appetitive drug memories undergo protein synthesis-dependent reconsolidation in the basolateral amygdala (BLA), an area important in the formation of emotional memories. We here investigated the importance of the BLA in the reconsolidation of opiate conditioned withdrawal memories. Rats with bilateral cannulas implanted in the BLA were trained to respond for heroin (0.12 mg/kg, i.v.) under a seeking-taking schedule, which required responding on a seeking lever to gain the opportunity to self-administer heroin by a single response on a taking lever. After induction of opiate dependence with subcutaneously implanted, heroin-filled osmotic minipumps (3 mg x kg(-1) x d(-1) heroin), rats received five consecutive pairings of a conditioned stimulus (CS) (tone, light, and odor compound) paired with naloxone (0.10 mg/kg, s.c.)-precipitated withdrawal. We replicated our previous findings that heroin seeking is suppressed in the presence of the withdrawal-associated CS. However, infusion of Zif268 antisense oligodeoxynucleotide into the BLA before reactivation of the CS-withdrawal association abolished this conditioned suppression in a reactivation-dependent manner. We also report that reconsolidation of CS-withdrawal memories upregulates Zif268 protein in the basolateral but not central nucleus of the amygdala and that Zif268 knockdown occurs selectively in the BLA. These results demonstrate that drug withdrawal memories undergo protein synthesis-dependent reconsolidation in the BLA and suggest a common mechanism for the reconsolidation of both appetitive and aversive drug memories.

Topics: Amygdala; Animals; Behavior, Addictive; Conditioning, Psychological; Early Growth Response Protein 1; Heroin; Heroin Dependence; Male; Memory; Rats; Substance Withdrawal Syndrome

The alteration of peripheral blood T-and B-lymphocyte proliferative responses were determined during different periods of withdrawal in heroin (Hw) and heroin / bhang (HBw) addicts. The results clearly demonstrated a significant decrease in the response of T- lymphocytes to PHA-stimulation and secretion of IL-2 in both Hw and HBw addicts. The in vitro presence of naloxone induced further inhibition of the PHA proliferative response and IL-2 production. Our data also indicated a significant suppression of IFN-gamma levels by human blood lymphocytes from Hw and HBw addicts. Additionally, a significant suppression of IFN-gamma production was demonstrated in the presence of naloxone. Moreover, IL-4 production was suppressed in Hw, but not in HBw groups and the in vitro presence of naloxone did not affect the level of IL-4 in both groups. However, IL-10 production was significantly increased in both groups accompanied by a significant suppression of IL-10 secretion in the presence of naloxone. In contrast, IL-5 levels stimulated by PHA showed a significant increase in both groups, while no significant effect of naloxone could be observed. Our results suggested that heroin administration can cause measurable suppression of some components of the human cellular immune system. The results further demonstrated that the immunsuppressive effect observed after heroin use are naloxone-mediated and suggested that activation of the adrenal gland is one potential mechanism for this effect.

Topics: Adrenocorticotropic Hormone; Adult; B-Lymphocytes; Heroin; Heroin Dependence; Humans; Hydrocortisone; Interferon-gamma; Interleukins; Lymphocyte Activation; Male; Naloxone; Narcotic Antagonists; Phytohemagglutinins; Substance Withdrawal Syndrome; T-Lymphocytes

The role of heroin-related stimuli in motivating the resumption of heroin use is not fully understood.. The objective was to characterize the relative importance of drug-related contextual stimuli, discriminative stimuli (DS), or discrete conditioned stimuli (CSs) on drug seeking when rats were reintroduced into the operant context after withdrawal.. Nose-poke responding by male rats was reinforced with intravenous heroin (0.05 mg/kg per infusion, 4-h session daily) under a progressive ratio schedule of reinforcement for 14 days. Each session began with the illumination of a green light in the active hole that served as DS. Each earned heroin injection was paired with a 5-s compound cue light and the sound of the infusion pump that served as the discrete CSs.. Response rates of heroin seeking induced by the contextual stimuli were comparable to the average rates of responding during self-administration training, but rates induced by either DS or CSs were greater than those induced by the contextual stimuli alone (P<0.05). The responding induced by contingent presentations of CSs was higher than that of DS after extinction of instrumental behavior. The drug seeking induced by CSs can be maintained after 3 days extinction with DS in the original context, although the responding elicited by DS cannot be recovered after 3 days of extinction with CSs.. The relapse to drug seeking can be elicited separately by environmental cues, heroin-predictive DS, or discrete CSs in the same rat after withdrawal.

Topics: Analgesics, Opioid; Animals; Cues; Disease Models, Animal; Extinction, Psychological; Heroin; Heroin Dependence; Infusions, Intravenous; Male; Rats; Rats, Sprague-Dawley; Recurrence; Reinforcement Schedule; Self Administration; Signal Detection, Psychological; Substance Withdrawal Syndrome; Time Factors

To make technical standard of acupuncture manipulation for acupuncture treatment of heroin withdrawal syndrome.. Two hundred and twenty cases of heroin withdrawal syndrome were randomly divided into an acupuncture group of 111 cases and a control group of 109 cases. They were respectively treated with acupuncture and oral administration of lofexidine hydrochloride, and their therapeutic effects were observed.. The heroin dependence (acute stage) were effectively withdrawn in the two groups. The treatment group in change of total scores for withdrawal symptoms before and after treatment, the total scores for withdrawal symptoms at the 4th and 5th days, treatment of insomnia and the score for self-Hamilton Anxiety Scale and the score after at the 4th day was superior to the control group (P < 0.05, P < 0.01, P < 0.001).. Acupuncture has a satisfactory, rapid, safe and reliable clinical therapeutic effect.

Topics: Acupuncture Therapy; Anxiety; Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

This paper describes the process evaluation of an out-patient detoxification service (ODS) established by Drug Health Services (DHS) to increase the supervised withdrawal options for substance users in a Sydney metropolitan Area Health Service. The ODS aimed to provide a safe and effective supervised withdrawal to substance users who were at low risk of severe withdrawal, engage those with severe dependence in further treatment and increase the involvement of general practitioners (GPs) in the medical care of ODS clients. During its first 10 months of operation, the ODS received 199 inquiries, assessed 82 individuals and admitted 76 clients for detoxification. Withdrawal treatment proceeded without complications and within the expected time frames. Fifty-four clients completed withdrawal, 10 ceased treatment, 10 remained in treatment without completing withdrawal and two were transferred elsewhere. Clients who injected substances (mainly heroin) daily at admission, compared to others, were less likely to complete withdrawal and more likely to use a range of non-prescribed substances during withdrawal. One-fifth of clients went on to further treatment with DHS, attending at least once. Overall, the ODS met its goals, providing a safe and effective supervised withdrawal to local residents, especially women, young people and those withdrawing from benzodiazepines who had significant substance dependence, impairment and previous alcohol and other drug (AOD) treatment. Non-injecting substance users benefited most from the ODS in terms of withdrawal completion and ongoing treatment. The level of GP involvement in the conjoint care of ODS clients remained constant over time. The development and expansion of the ODS are discussed.

Topics: Adolescent; Adult; Anxiety; Benzodiazepines; Cannabis; Depression; Ethanol; Evaluation Studies as Topic; Female; Heroin; Humans; Male; Middle Aged; New South Wales; Outpatients; Stress, Physiological; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Substance-Related Disorders

Young and middle-aged CBA mice were injected with "street" heroin in increasing doses for 14 days. Volume density of perisinusoid argirophilic fibers increased in both age groups (the increase being more pronounced in middle-aged mice), while the levels of spontaneous, LPS- and ConA-stimulated splenocyte proliferation decreased in young mice. Six months after heroin discontinuation further progress of liver fibrosis was observed in young mice.

Topics: Age Factors; Animals; Cells, Cultured; Concanavalin A; Fibrosis; Heroin; Lipopolysaccharides; Liver; Mice; Mice, Inbred CBA; Spleen; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

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

Using a rat relapse model, recent studies reported time dependent increases in cocaine seeking induced by re-exposure to cocaine cues, but not cocaine itself, over withdrawal periods of up to 3 months.. In the present study, we explored the time course of cocaine seeking induced by priming injections of heroin over the first 3 months of withdrawal from cocaine.. Rats were trained to self-administer intravenous cocaine for 6 h/day over a period of 10 days. Cocaine seeking induced by heroin priming was then assessed in different groups of rats after 1 day, and 1 and 3 months of withdrawal from cocaine. During the test day, rats were first given six 1-h extinction sessions. Subsequently, reinstatement of cocaine seeking induced by non-contingent saline and heroin injections (0.125 and 0.25 mg/kg, s.c.) was assessed during three 1-h sessions.. As in previous studies, extinction responding was substantially greater after 1 and 3 months of withdrawal than after 1 day. More importantly, we also found that the effect of heroin priming on reinstatement of cocaine seeking is time dependent, with higher responding occurring after 1 and 3 months than after 1 day.. The present results replicate previous findings on the time dependent increases in resistance to extinction after withdrawal from cocaine, and further indicate that the duration of the drug withdrawal period is a critical modulator of the effect of heroin priming on cocaine seeking. These data may have implications for the treatment of cocaine relapse induced by other drugs.

Topics: Animals; Behavior, Addictive; Cocaine; Conditioning, Operant; Disease Models, Animal; Drug Administration Schedule; Extinction, Psychological; Forecasting; Heroin; Injections, Intravenous; Injections, Subcutaneous; Male; Rats; Rats, Long-Evans; Recurrence; Self Administration; Substance Withdrawal Syndrome; Time Factors

An evaluation of time perception in drug addicts was carried out in 12 s intervals, using 10 attempts with up to 0.1 s precision. Eighty-two heroin addicts in abstinent and post abstinent periods have been observed, the results being compared to 52 healthy controls. During the first two days after admission to the hospital (abstinent syndrome development), time intervals values were lower in patients than in controls, reaching a precision of recalling 12s, with a following exceeding of this index. On day 15-16, time perception returned to precise level (post abstinent period). Depending on drug addiction duration and individual features of brain hemisphere asymmetry, changes in subjective time perception were revealed in the study.

Topics: Adolescent; Adult; Brain; Functional Laterality; Heroin; Heroin Dependence; Hospitalization; Humans; Length of Stay; Male; Severity of Illness Index; Substance Withdrawal Syndrome; Time Factors

Environmental stimuli and conditioned cues associated with heroin can induce drug-seeking behavior, but how heroin lapse interacts with cues is unclear. Rats were trained to nose-poke for i.v. heroin for 14 days and then tested for heroin seeking after withdrawal from heroin self-administration. Heroin seeking induced by cues persisted over several weeks after withdrawal, and the responding was not easily extinguished after 4 weeks withdrawal. A single injection of heroin (250 micro g/kg) enhanced the responding at early stage of withdrawal, but a low dose of heroin (50, 250 micro g/kg) suppressed the responding induced by contextual or conditioned cues at 4 weeks of withdrawal. The results suggest that prolonged withdrawal may increase the risk of relapse to heroin seeking.

Topics: Animals; Conditioning, Operant; Cues; Disease Models, Animal; Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Male; Rats; Rats, Sprague-Dawley; Recurrence; Reward; Risk Factors; Self Administration; Substance Withdrawal Syndrome; Time Factors

Working memory (WM) and attentional deficits have been implicated in the pathophysiology of both obsessive-compulsive disorder (OCD) and opioid addiction. The P300 component of event-related potentials (ERPs) is considered as an index of on-line updating of WM and/or attentional operations involved in this function. The present study aimed at comparing the P300 elicited during a WM test in patients with prolonged heroin abstinence, those with OCD and healthy controls, in order to demonstrate possibly common underlying psychophysiological mechanisms.. The P300 component was evaluated during the anticipatory period of a WM test in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 OCD patients, and 20 healthy subjects matched for age, sex and educational level.. The two patient groups showed a considerable reduction of the P300 amplitudes, located at the right frontal area as compared with healthy controls. The abstinent heroin addicts exhibited a significantly lower P300 amplitude at central frontal areas and a significantly higher P300 amplitude at the left occipital region relative to the other two groups. Furthermore, the abstinent group showed a notable delay of P300 latency relative to controls and OCD patients at the right occipital region. Moreover, the OCD patients manifested a significant prolongation of P300 located at the central prefrontal area, relative to addicts and healthy controls.. These findings point to considerable WM and/or attentional deficits in the long-term abstinent syndrome of heroin misuse and OCD associated with distributed and prefrontal cortical circuits, respectively. Furthermore, the present findings suggest that both OCD and long-term abstinent heroin addicts may share a common impairment of WM and/or attention involving or affecting the right prefrontal areas.

Topics: Adult; Attention; Event-Related Potentials, P300; Female; Heroin; Humans; Male; Memory; Obsessive-Compulsive Disorder; Reaction Time; Substance Withdrawal Syndrome

Topics: Adolescent; Comorbidity; Drug Tolerance; Heroin; Heroin Dependence; Humans; Mental Disorders; Narcotics; Practice Guidelines as Topic; Substance Withdrawal Syndrome; Treatment Outcome; United States

We report on a series of patients with acute strabismus related to heroin and methadone intake or withdrawal, discuss possible mechanisms involved in this clinical picture and make recommendations for work-up and referral.. Retrospective study.. Five patients presented with acute esotropia within days of heroin withdrawal, and two patients developed exotropia related to heroin or methadone intake. Neurological work-up and neuroimaging was non-contributory in all four patients who were examined.. Acute esotropia with double vision is a disturbing side effect of heroin withdrawal, and, similarly, acute exotropia may be related to heroin intake. In the absence of focal neurological signs, further work-up is not mandatory. Referral to a specialised orthoptic service is beneficial in offering the patient symptomatic treatment and reassurance, thus supporting successful withdrawal therapy.

Topics: Adult; Diplopia; Esotropia; Female; Heroin; Humans; Male; Methadone; Narcotics; Retrospective Studies; Substance Withdrawal Syndrome

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

The purpose of this study was to determine the significance of chronic opioid exposure on the level of heroin self-administration in the rat. Rats were divided into morphine (M, subcutaneous morphine pellets) and placebo (P, subcutaneous placebo pellets) groups and self-administered several different doses of heroin during daily limited access 1-h sessions and prolonged access 8-h sessions. No effects on heroin self-administration occurred when the rats were implanted with morphine pellets and allowed to self-administer heroin in a limited access paradigm (1-h group). However, rats with morphine pellet implantation showed a rapid escalation (Days 0-3 post-pellet) in heroin self-administration in the more prolonged access group (8 h group) compared to placebo-pelleted animals also with 8-h access. Ultimately, placebo-pelleted 8-h exposed animals showed an escalation in heroin self-administration but this effect was delayed until Days 16-18 post-pellet. These results suggest that passive administration of morphine sufficient to produce and maintain dependence facilitates escalation in heroin intake.

Topics: Animals; Dose-Response Relationship, Drug; Drug Implants; Heroin; Heroin Dependence; Male; Morphine; Narcotics; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome

Topics: Esotropia; Exotropia; Health Care Costs; Heroin; Humans; National Health Programs; Nystagmus, Pathologic; Reoperation; State Medicine; Strabismus; Substance Withdrawal Syndrome; United States; Vision, Monocular

Esotropia during opiate withdrawal is a new clinical syndrome that has only recently been reported in the literature.. Clinical case series.. Five patients with acute esotropia during opiate withdrawal are presented. In four there was evidence of underlying hyperopia and/or other strabismogenic features.. The precise cause of esotropia with heroin withdrawal is uncertain. Most (and possibly all) of these patients have one or more objective strabismogenic features, and these are probably a large factor in the causation.

Topics: Acute Disease; Adult; Disease Susceptibility; Esotropia; Female; Heroin; Humans; Male; Substance Withdrawal Syndrome

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

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

We examined the role of withdrawal in relapse to drug-seeking and drug-taking by testing the effects of opiate abstinence on extinction behaviour in rats trained to self-administer heroin. Male Long-Evans rats responded for IV heroin under a heterogeneous chain (VI 120 s; FR 1) schedule in which "seeking" responses preceded a "taking" response which produced a drug infusion. Responding was then measured in extinction during acute (6, 12, and 24 hr) and prolonged (3, 6, 12, and 25 day) abstinence. Sucrose consumption and somatic withdrawal were assessed at each testing period. During acute abstinence, responses on the "drug-seeking" manipulandum increased at 24 hr, whereas responses on the "drug-taking" manipulandum increased at 6 hr. Both responses were elevated during the 12-day abstinence test. Sucrose consumption was reduced and somatic withdrawal scores were increased in opiate-experienced rats at each test period. Results suggest that heroin abstinence has different effects on drug-seeking and drug-taking and that these effects do not temporally coincide with somatic measures of opioid withdrawal.

Topics: Acute Disease; Animals; Conditioning, Operant; Disease Models, Animal; Extinction, Psychological; Heroin; Heroin Dependence; Male; Rats; Rats, Long-Evans; Self Administration; Substance Withdrawal Syndrome

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

Heroin beckons like the sweet seductive calls of Ulysses' sirens. The alluring nectar of the poppy seed, once experienced is not easy to escape. The greed for pleasure is endless. Gratification begets gratification. This paper explores issues and complications of treatment intervention in heroin addiction. The author is a general practitioner with 25 years experience and special interest in substance abuse medicine.

Topics: Australia; Combined Modality Therapy; Heroin; Humans; Prognosis; Rehabilitation; Risk Assessment; Risk-Taking; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

To report the possible effects of heroin withdrawal on binocular vision.. A case series of patients is presented in whom esotropia developed on cessation of heroin use.. In each case the esotropia was concomitant and prismatic correction restored binocular single vision. Intermittent spontaneous control occurred in one patient, the deviation resolved in one and one patient was lost to follow-up.. Heroin withdrawal should be considered as a cause of acute concomitant esotropia. However, an accurate history of other medication is needed to ensure that this is not the cause of decompensation.

Topics: Acute Disease; Adult; Esotropia; Female; Follow-Up Studies; Heroin; Humans; Male; Narcotics; Substance Withdrawal Syndrome

It is difficult to conceive that tolerance and sensitization processes, two apparently opposite phenomena, can concomitantly modify one given biological process, i.e., the processing of pain. We have shown recently that opiates produce not only analgesia but also long-lasting hyperalgesia in rats. This suggests that tolerance to the analgesic effect of an opiate, especially heroin, could be in part the result of an actual sensitization of pronociceptive systems. Here, we show that both magnitude and duration of heroin-induced delayed hyperalgesia increase with intermittent heroin administrations, leading to an apparent decrease in the analgesic effectiveness of a given heroin dose. Our observation that a small dose of heroin which is ineffective for triggering a delayed hyperalgesia in non-heroin-treated rats induced an enhancement in pain sensitivity for several days after a series of heroin administrations is in agreement with the sensitization hypothesis. The effectiveness of the opioid receptor antagonist naloxone to precipitate hyperalgesia in rats that had recovered their pre-drug nociceptive value after single or repeated heroin administrations indicates that heroin-deprived rats were in a new biological state associated with a high level balance between opioid-dependent analgesic systems and pronociceptive systems. Because the NMDA receptor antagonist dizocilpine maleate (MK-801) prevented both heroin-induced long-lasting enhancement in pain sensitivity and naloxone-precipitated hyperalgesia, these findings further suggest that tolerance, sensitization, and one withdrawal symptom, hyperalgesia, are issued from a neuroadaptive process in which NMDA systems play a critical role.

Topics: Animals; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Excitatory Amino Acid Antagonists; Heroin; Heroin Dependence; Hyperalgesia; Injections, Subcutaneous; Male; Naloxone; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome

The P600 component of event-related potentials, believed to be generated by anterior cingulate gyrus and basal ganglia, is considered as an index of aspects of second-pass parsing processes of information processing, having much in common with working memory (WM) systems. Moreover, dysfunction of these brain structures as well as WM deficits have been implicated in the pathophysiology of opioid addicts. The present study is focused on P600 elicited during a WM test in twenty heroin addicts with prolonged abstinence compared with an equal number of healthy controls. The results showed significantly prolonged latencies at right hemisphere, specifically at Fp2 abduction. Moreover, memory performance of patients did not differ from that of normal controls. These findings may indicate that abstinent heroin addicts manifest abnormal aspects of second-pass parsing processes as are reflected by the P600 latencies, elicited during a WM test. Additionally, the P600 might serve as a valuable investigative tool for a more comprehensive understanding of the neurobiological substrate of drug abuse.

Topics: Adult; Brain; Evoked Potentials; Female; Heroin; Heroin Dependence; Humans; Male; Memory; Reference Values; Substance Withdrawal Syndrome; Time Factors

Footshock stress reliably reinstates heroin seeking in rats, but the time course of the development of this effect following drug withdrawal is not known. Here we studied the effect of intermittent footshock stress on reinstatement of heroin seeking following different withdrawal periods (1-66 days). We also studied whether changes in corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) are correlated with this reinstatement after 1 day and 6 days of heroin withdrawal.. Rats were trained to self-administer heroin (9 h/day; 0.1 mg/kg per infusion) for 10 days. Tests for extinction behavior and footshock-induced reinstatement of heroin seeking were then conducted after 1, 6, 12, 25, or 66 days of heroin withdrawal. On the test day, rats were given five to ten 60-min extinction sessions until they reached the extinction criterion of less than 15 responses per 60 min on the lever previously associated with heroin. Rats were then exposed to intermittent foot-shock (0.8 mA; 10 min), and lever-pressing behavior was recorded for 120 min.. Reinstatement of lever-pressing behavior by footshock followed an inverted U-shaped curve with maximal responding after 6 days and 12 days of heroin withdrawal. Surprisingly, foot-shock did not reinstate lever-pressing behavior on day 1 of withdrawal. Lever pressing during extinction, prior to exposure to footshock, also followed an inverted U-shaped curve, with higher responding after 6, 12, and 25 days of heroin withdrawal. Finally, compared with control groups not exposed to shock, CRF mRNA levels in response to footshock were increased in the CeA (day 1 of withdrawal) and the dorsal BNST (day 1 and day 6), but not in the ventral BNST.. The duration of the heroin withdrawal period is an important factor in the manifestation of (1) footshock stress-induced reinstatement of heroin seeking and (2) extinction of the heroin-reinforced behavior. Finally, the time-dependent changes in footshock stress-induced reinstatement following withdrawal from heroin were not correlated with alterations in CRF mRNA in the CeA and BNST.

Topics: Animals; Behavior, Addictive; Brain; Corticotropin-Releasing Hormone; Extinction, Psychological; Heroin; Male; Narcotics; Rats; Rats, Long-Evans; Self Administration; Stress, Physiological; Substance Withdrawal Syndrome; Time Factors

The compulsive nature of heroin abuse has been attributed to the fact that drug self-administration enables an addict to escape from and avoid the severe withdrawal symptoms resulting from opiate dependence. However, studies of incentive learning under natural motivational states suggest an alternative hypothesis, that withdrawal from heroin functions as a motivational state that enhances the incentive value of the drug, thereby enabling it to function as a much more effective reward for self-administration. In support of this hypothesis, we show here that previous experience with heroin in withdrawal is necessary for subsequent heroin-seeking behavior to be enhanced when dependent rats once again experience withdrawal.

Topics: Animals; Avoidance Learning; Behavior, Animal; Heroin; Heroin Dependence; Male; Rats; Rats, Inbred Strains; Reward; Self Administration; Substance Withdrawal Syndrome

From July 1999 it became evident that a rising number of heroin users were presenting to the Dandenong Hospital Emergency Department with a rapid onset, florid opioid withdrawal syndrome following the intravenous injection of what they had believed to be heroin. We suspect that the injected substance was in fact naltrexone. This paper describes two such cases and reviews the literature on naltrexone. Recommendations regarding the management of the acute opioid withdrawal syndrome are made.

Topics: Acute Disease; Adult; Colic; Emergency Medical Services; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Naltrexone; Narcotics; Substance Withdrawal Syndrome; Vomiting

We explored the frequency of commencing opiate use by "chasing the dragon" to "come down" off Ecstasy and the stability of heroin smoking in young opiate takers by assessing 102 subjects in Dublin using a semistructured interview. Ninety-two subjects had used Ecstasy. Of these, 68 reported "chasing" to "come down" off Ecstasy at some point in their history and were found to have used Ecstasy more frequently and in larger amounts. Thirty-six reported that their first experience of using opiates was to "come down" off Ecstasy, 28 citing this as their main reason for commencement.Eighty-six of the 102 commenced opiates by "chasing" heroin, 61 of whom progressed to injecting after a mean of 2.9 years. This was associated with starting illicit drug use earlier, starting heroin earlier, and a history of using Ecstasy. Implications for service planners in developing responses to illicit drug use among adolescents are discussed.

Topics: Administration, Inhalation; Adolescent; Adult; Heroin; Heroin Dependence; Humans; Ireland; N-Methyl-3,4-methylenedioxyamphetamine; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

The use of naloxone hydrochloride (0.2-0.4 mg) in complex therapy of adolescent heroin addicts significantly prolonged the half-life of serum leu-enkephalin, slightly elevated the thresholds of thermal nociceptive reactions, and improved some clinical indices (considerably reduced drug addiction, eliminated affective disorders, etc.), which are important for deactualization of drug addiction and promoting remission.

Topics: Adolescent; Age Factors; Heroin; Humans; Male; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome; Substance-Related Disorders; Temperature; Time Factors

One of the treatment alternative of withdrawal symptoms of patients suffering from opiate dependence is to apply the clonidine in combination or itself. This remedy is not in commercial trade in our country. It is expectable according to the recent data analysing the effects of the alfa2 adreneregic agonist tizanidine that tizanidine has the similar protective effect as clonidine with the resembling target point. Based on this theory a research was done, in the course of which the i.v. heroin users who presented themselves at the Drug Outpatient Department of Buda between 1.10.1998-8.01.1999. were divided into two groups. The groups had got the usual detoxification treatment, but in the experimental group tizanidine were given in 3 x 8 mg/day dose too. Sixteen patients were in the tizanidine group, 10 patients were in the control group. The patients estimated the intensity of 7 symptoms of withdrawal (sweating, nervousness, insomnia, tremor, diarrhoea, muscle pain, drug craving) on a subjective scale day by day. The analysis showed that the tizanidine treatment decreased the intensity of the withdrawal symptoms in every symptom type examined. The ten days long acute withdrawal period were accomplished by all of the patients, but in the short course of the following (mean 9 and 11 weeks in the treated and the control groups respectively) there were three relapses in each group (3/16 in the treated and 3/10 in the control).

Topics: Acute Disease; Adult; Analgesics; Anticonvulsants; Case-Control Studies; Clonidine; Female; Heroin; Heroin Dependence; Humans; Male; Muscle Relaxants, Central; Narcotics; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Chlorpromazine; Diplopia; Heroin; Humans; Male; Substance Withdrawal Syndrome

The purpose of the current study was to assess neuropeptidergic alterations during a phase of the drug addiction cycle associated with drug craving as compared to a time period when the drug had been recently self-administered. Male Wistar rats were allowed to self-administer cocaine, heroin or saline for 6 h for 5 consecutive days. Immediately following the last self-administration session ('acute drug on board' state), and just before the next scheduled session ('drug expecting' state), the animals were decapitated and the levels of dynorphin A and B, [Met5]- and [Leu5]-enkephalin and substance P were measured in different brain areas. During the 'acute drug on board' state, peptide levels in animals that self-administered heroin or cocaine were not significantly changed. In contrast, during the 'drug expecting' state, heroin-treated animals had increased levels of dynorphin A, dynorphin B and [Met5]-enkephalin in the caudal striatum as compared to the cocaine- and saline-treated animals, and the level of [Leu5]-enkephalin was increased as compared to the cocaine-treated group. In the septum, an increase of [Met5]-enkephalin and substance P was observed in the animals expecting heroin as compared to the saline- and/or cocaine-treated animals. In the caudal striatum, substance P levels were elevated in the heroin- and cocaine-expecting animals. In conclusion, heroin, as compared to cocaine, appears to have a more pronounced effect on dynorphin, enkephalin and substance P levels in the caudal striatum and septum, especially during periods when self-administration of the drug is expected.

Topics: Animals; Behavior, Animal; Brain; Cocaine; Dynorphins; Enkephalins; Heroin; Injections, Intravenous; Male; Neuropeptides; Radioimmunoassay; Rats; Rats, Wistar; Self Administration; Substance P; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

The neurobiological mechanisms underlying the persistence of drug craving in detoxified addicts are still poorly understood.. The present study was designed to evaluate dopaminergic mechanisms in drug-seeking behaviour following long-term (>3 weeks) extinction of IV drug self-administration in rats.. To that end, we studied the effects of direct and indirect dopamine (DA) agonists on reinstatement of previously extinguished responding for heroin (50 microg/kg per injection; 14-15 daily 3-h sessions) and cocaine (500 microg/kg per injection; 10-11 daily 2-h sessions).. In animals with a cocaine history, priming with cocaine, the selective DA reuptake inhibitor GBR-12909 and the DA D2 receptor agonist quinpirole resulted in robust and selective reinstatement of non-reinforced nose poking behaviour in the previously drug-paired hole. In contrast, the D1 agonist SKF-82958 failed to reinstate responding and the non-selective DA agonist apomorphine even suppressed responding in these animals. In heroin-trained rats, heroin and GBR-12909 strongly reinstated responding, whereas all direct DA agonists were ineffective. Again, the two highest doses of apomorphine decreased responding in these animals. In a parallel study, the ability of DA ligands to express behavioural sensitization in animals pretreated with amphetamine or morphine was evaluated. Interestingly, all agonists that reinstated responding in the present study caused expression of locomotor sensitization and vice versa.. The differences between direct and indirect agonists indicate a clear, but complex, involvement of DA in drug-seeking behaviour long after detoxification. Moreover, the results show an important role of D2 receptor activation in the persistence of cocaine- but not heroin-seeking behaviour. Finally, the results from both studies suggest a relationship between drug-induced reinstatement and drug hyperresponsiveness in long-term abstinent rats.

Topics: Animals; Behavior, Addictive; Benzazepines; Cocaine; Dopamine Agonists; Dopamine Uptake Inhibitors; Heroin; Male; Narcotics; Piperazines; Quinpirole; Rats; Rats, Wistar; Receptors, Dopamine; Substance Withdrawal Syndrome

Non-dependent and dependent opiate users appear to be driven by two distinct motivational factors: the primary reinforcing properties of the drug, and the negative reinforcing effects associated with relieving the negative affective component of opiate withdrawal in the dependent state.. To investigate the motivational significance of opioid dependence on heroin self-administration (HSA) in rodents.. Rats were trained to self-administer heroin intravenously (0.06 mg/kg per infusion; FRI), and opiate dependence was induced by subcutaneous implantation of two morphine (75 mg base) pellets. Rats in a non-dependent control group received placebo pellets. Three days after pellet implantation, HSA was resumed in daily 3-h sessions until baseline criteria were met and testing was conducted with subcutaneous injections of vehicle or naloxone (0, 0.003, 0.01, 0.03 mg/kg) 115 min into the session.. Morphine-dependent rats significantly increased HSA upon 0.01 mg/kg naloxone treatment, but decreased response rates at 0.03 mg/kg. Placebo pellet-implanted rats increased heroin intake at the 0.01 and 0.03 mg/kg doses. In a second experiment, the HSA session was shortened to 1 h and the training dose reduced to 0.03 mg/kg per infusion in new groups of animals. HSA in placebo pellet-implanted rats was increased only following the highest dose of the antagonist, while dependent rats were still affected by naloxone doses of 0.003-0.03 mg/kg. When subjected to a progressive-ratio schedule (experiment 3), breaking point values in dependent animals were 198% above baseline.. The present study supports the hypothesis that dependence-induction by morphine-pellet implant in rats resulted in increased sensitivity to very small naloxone doses, as measured by changes in HSA. Taken together, these data suggest that opiate dependence, as measured by changes in sensitivity to naloxone, is a continuum which can contribute to the motivational state of drug-seeking.

Topics: Animals; Heroin; Illicit Drugs; Male; Morphine; Morphine Dependence; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome

Topics: Adult; Combined Modality Therapy; Female; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Moscow; Narcotics; Preoperative Care; Substance Withdrawal Syndrome; Surgical Procedures, Operative

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

To determine the relationship between severity of opiate withdrawal and prior heroin dose and route of administration (smoking versus intravenous injection).. Retrospective analysis of withdrawal data and assessment of associations with baseline variables including heroin dose, route of administration, duration of use, concomitant use of cocaine, severity of opiate dependence, previous treatment, sex or age.. Psychiatric inpatient unit specialized in withdrawal treatments.. Twenty-two opiate addicts injecting or smoking heroin who were abruptly withdrawn after admission.. Daily assessment of withdrawal severity with the Opiate Withdrawal Scale (OWS) during the first week after drug cessation.. Severity and duration of withdrawal symptoms were greater in injectors compared to smokers (with comparable doses) and also in patients with higher heroin dose. Heroin dose and route of administration were related significantly to total and maximum withdrawal scores and together accounted for about 50% of variance. Similar levels of total withdrawal distress were associated with approximately five times higher heroin consumption in chasers than in injectors.. The impact of heroin dose and route of administration on withdrawal severity is marked. The influence of the route of administration on withdrawal severity might be due to differences in bioavailability.

Topics: Adult; Biological Availability; Drug Administration Routes; Female; Heroin; Heroin Dependence; Humans; Male; Narcotics; Retrospective Studies; Severity of Illness Index; Smoking; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Topics: Adrenergic alpha-Agonists; Animals; Blood Pressure; Clonidine; Guanfacine; Heart Rate; Heroin; Heroin Dependence; Rats; Substance Withdrawal Syndrome; Time Factors

Topics: Emergency Service, Hospital; Heroin; Humans; Naltrexone; Narcotic Antagonists; Patient Discharge; Substance Withdrawal Syndrome

Dihydroetorphine is a novel opioid that is an extremely potent analgesic in rodents. The reinforcing potency was determined in rats trained to self-administer heroin and compared to those of fentanyl, heroin, 6-acetylmorphine and morphine for assessment of the abuse potential of dihydroetorphine using a procedure that determines the dose-effect curve in individual sessions. Dihydroetorphine produced a bimodal dose-effect curve similar to that of other opioids. Potency ratios were determined with morphine for the ascending and descending limbs of the dose-effect curve, as well as the dose that yielded maximal response rate. Fentanyl, heroin and 6-acetylmorphine were approximately 100, 8 and 2 times more potent than morphine in maintaining self-administration, respectively. Dihydroetorphine was roughly 1500 to 3000 times more potent than morphine, however, depending upon the limb of the dose-effect curve used for comparison. These potency ratios of dihydroetorphine to morphine were somewhat less than has been reported for analgesia assays, and therefore this compound may have some clinical advantages over other opioids. However, these studies indicate significant abuse liability for dihydroetorphine given its potency in maintaining self-administration in these animals.

Topics: Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Etorphine; Fentanyl; Heroin; Male; Morphine; Morphine Derivatives; Rats; Rats, Inbred F344; Substance Withdrawal Syndrome; Substance-Related Disorders

Blood pressure and heart rate were monitored in heroin addicts detoxified with guanfacine in an outpatient program. Retrospective analysis of the cardiovascular parameters from the addicts who failed this detoxification during the first 5 days of treatment (they consumed heroin within this period) showed that these patients experienced less hypotension and bradycardia when treated with the alpha 2-agonist than the group of successful patients. Therefore, the relapse to opiate use could be predicted, at least in some patients, by a minimal cardiovascular reaction to guanfacine. Opiate use was followed by significant increases in blood pressure and heart rate, as had happened in previous studies with clonidine-treated addicts. This finding further confirms a similarity between alpha 2-agonists adrenergic and opiates with regard to their cardiovascular effects.

Topics: Adrenergic alpha-Agonists; Blood Pressure; Guanfacine; Heart Rate; Heroin; Heroin Dependence; Humans; Male; Substance Withdrawal Syndrome

Craving is a significant factor in opiate addiction that is associated with drug-dependence and in relapse to drug use after treatment. In order to better understand the psychological and physiological mechanisms of craving for opiates, we have developed an imagery-based procedure using personal verbal descriptions of craving in abstinent opiate addicts. Thirteen opiate addicts in detoxification were required to imagine and describe their craving experiences while autonomic measures of heart rate and arterial pressure were taken. Subjects displayed a significant increase in systolic blood pressure and heart rate while describing drug craving compared with neutral descriptions. Furthermore, an increase in systolic blood pressure during imagery of craving descriptions compared with neutral descriptions was observed. These results provide preliminary evidence that imagery is powerful in eliciting craving for opiates, as indicated by subjective ratings and autonomic measures. The implications of the results of this paper for the cue-exposure paradigm and contemporary models of addiction are being discussed.

Topics: Adult; Arousal; Autonomic Nervous System; Blood Pressure; Heart Rate; Heroin; Heroin Dependence; Humans; Imagination; Male; Motivation; Narcotics; Pain Measurement; Patient Admission; Personality Inventory; Self Concept; Substance Withdrawal Syndrome

The similarity between opiate withdrawal and migraine (M) has been confirmed regarding increased monoamine sensitivity at the neuromuscular junction of the hand's dorsal vein as well as at the neuraxis where dopamine (DA) supersensitivity was observed. Similarities also included an increase in cAMP levels as a precocious sign in both M and opiate withdrawal. Particular attention has been devoted to the time-course of monoamine supersensitivity in M and in abstinence. It has been found that the maximum level of super-sensitivity occurs in M at the end of the M attack, whereas the maximum super-sensitivity is present at the very beginning of opiate abstinence. The inverse time-course of this phenomenon suggests that it could play some pathophysiological role in inducing the end of the M attack. Conversely, it can represent the expected transient result of a pharmacological denervation which ought to result in a supersensitivity of opioid-dependent neuron during withdrawal. In M, the super-sensitivity is wider, indeed, it involves more receptor types. This could be an indirect proof of the involvement of inhibitory pathways other than the opioidergic one.

Topics: Adult; Biogenic Monoamines; Female; Heroin; Humans; Male; Migraine Disorders; Substance Withdrawal Syndrome

Numerous studies reported in recent years have shown that withdrawal from chronic consumption of drugs induces high levels of anxiety, both in humans and in animal models. In the present study, we demonstrated that withdrawal from chronic consumption of either ethanol or heroin causes a significant increase in plasma nerve growth factor, suggesting that the resulting anxiety condition triggers the release of this molecule. Although the functional significance of this phenomenon needs to be better defined, it is hypothesized that the increased levels of circulating nerve growth factor might be involved in homeostatic adaptive and/or reparative mechanisms.

Topics: Adult; Aged; Alcohol Withdrawal Delirium; Alcoholism; Animals; Anxiety; Arousal; Corticotropin-Releasing Hormone; Female; Heroin; Heroin Dependence; Homeostasis; Humans; Male; Middle Aged; Nerve Growth Factors; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome

It is widely believed that opioid withdrawal symptoms contribute to relapse to opioid use, but relapse is highly probable in experienced users even after prolonged abstinence and during opioid maintenance therapy. We have found using an animal model of relapse, the reinstatement procedure, that the two events that reliably reinstate heroin-seeking behavior are reexposure to heroin, and brief exposure to footshock stress. Contrary to expectation, opioid antagonist-induced withdrawal does not reinstate heroin-seeking. We now report on reinstatement of heroin-seeking in rats trained to self-administer heroin and subsequently exposed to a maintenance dose of heroin via minipump and allowed to self-administer saline. With the minipump in, naloxone-induced withdrawal did not reinstate drug-seeking, a priming injection on heroin was only mildly effective, and footshock was highly effective. Twenty-four hours after removal of the minipump (spontaneous withdrawal), animals reinitiated heroin-seeking and, subsequently, both heroin and footshock reinstated heroin-seeking. In summary, brief exposure to stress reinstated heroin-seeking in both heroin-maintained and withdrawn animals. The heroin prime reliably reinstated drug-seeking only in the absence of the minipump; opioid "withdrawal," as such, did not reinstate drug-seeking behavior. Naloxone given to heroin-maintained animals induced withdrawal symptoms, caused a mild depression in the levels of dopamine and its metabolites in the nucleus accumbens septi (NAS), but did not reinstate drug-seeking. Reinstatement of heroin-seeking during spontaneous withdrawal was not accompanied by reductions in basal dopamine and its metabolites in NAS.

Topics: Animals; Electroshock; Heroin; Heroin Dependence; Infusion Pumps; Male; Microdialysis; Naloxone; Rats; Rats, Inbred Strains; Recurrence; Self Administration; Stress, Physiological; Substance Withdrawal Syndrome

The purpose of this study was to determine if cerebral blood flow (CBF) alterations are associated with discontinuation of heroin in chronic heroin users, and whether these alterations are reversible during abstinence. Ten physically healthy opioid-dependent males, hospitalized on an inpatient drug rehabilitation unit, were studied. Each patient had an initial single photon emission computed tomographic (SPECT) scan with the radiotracer technetium-99m-d,l-hexamethylpropyleneamine oxime (99mTc-HMPAO) 1 week after opiate discontinuation and a repeat scan 2 weeks later. The initial scans in 9 of the 10 subjects demonstrated significant, often discrete, perfusion defects, especially in the frontal, parietal, and temporal cortices. Two weeks later, repeat brain perfusion SPECT scans showed improvement in all nine subjects who had abnormal scans. Comparisons of the first scan with the second scan showed an increase in cortical uptake on the repeat SPECT study. All subjects had normal computed tomographic or magnetic resonance imaging scans. The results of this preliminary study suggest that the chronic use of opiates, like chronic use of cocaine, results in perfusion abnormalities without corresponding abnormalities on imaging studies of cerebral anatomy and morphology. This study also documents that these perfusion defects are partially reversible with short-term abstinence.

Topics: Adult; Brain; Cerebellum; Heroin; Humans; Male; Middle Aged; Substance Withdrawal Syndrome; Technetium Compounds; Tomography, Emission-Computed, Single-Photon

The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known to have been a heroin addict and to have taken other psychoactive substances, who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic examination showed generalized visceral congestion, edema and pulmonary anthracosis, chronic bronchitis and chronic active hepatitis. Toxicological findings included fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood), 84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine), 57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and 0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference to its therapeutic use and to reports of non-fatal GHB intoxication.

Topics: Adult; Fatal Outcome; Heroin; Heroin Dependence; Humans; Male; Sodium Oxybate; Substance Withdrawal Syndrome

Substance abuse is associated diagnostically with existing depression, pathological mourning of the traumatic event itself, with the inevitable experience of object loss, and loss of love. Inability to form object representation insures primitive lack of object constancy, resulting in pre-oedipal longing and neediness and malignant affect. Ambivalence towards the sadistic love objective is recognized and allows for a healthier, more complete period of mourning (Freud, 1917). Indeed, depression is banished from family acknowledgement in the service of homeostatic denial. This only reinforces the identified patient's feeling of unreality, shame and guilt over verbalizing the depression and the frequent underlying traumatic history. The enormous role of socio-economic stress is pervasive, yet the focus here is on individuals with complex dynamic constellations which are often ignored in the face of external factors. Addiction as attempt to self-medicate depression and trauma remains the overarching theme.

Topics: Adult; Depressive Disorder; Female; Heroin; Humans; Psychoanalytic Therapy; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Buprenorphine; Clinical Trials as Topic; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Quality of Life; Social Support; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

The researchers studied whether 2 separate motivational systems in the brain underlie the rewarding effects of morphine. The brainstem tegmental pedunculopontine nucleus (TPP) is involved in mediating the motivational effects of opiates in nondeprived (drug-naive) rats, whereas dopamine transmission is necessary in mediating the motivational effects of opiates in deprived rats (opiate withdrawal). The results show that heroin's motivational properties obey the same boundary between a nondeprived and a deprived motivational state. Bilateral ibotenic acid lesions of the TPP blocked the acquisition of a place preference for an environment paired with 0.05 mg/kg heroin (a dose that induces no withdrawal aversion) but had no effect on place preference for an environment paired with 0.5 mg/kg heroin (a dose that does induce withdrawal aversion). Dopamine antagonist pretreatment produced the opposite pattern of results.

Topics: Animals; Antipsychotic Agents; Avoidance Learning; Brain Mapping; Brain Stem; Conditioning, Classical; Dopamine; Dose-Response Relationship, Drug; Flupenthixol; Heroin; Heroin Dependence; Male; Motivation; Pimozide; Premedication; Rats; Rats, Wistar; Social Environment; Substance Withdrawal Syndrome; Synaptic Transmission

This paper reports the DHE substitution clinical trial in 38 heroin addicts. The CINA (Clinical Institute Narcotic Assessment) scale was used to assess physical dependence potential. The CINA scale contains 10 opioid withdrawal signs (nausea, vomiting, gooseflesh, sweating, restlessness, tremor, larcrimation, nasal congestion, yawning, changes in heart rate and systolic blood pressure) and 3 opiate withdrawal symptoms (abdominal pain, muscle pain and feeling hot or cold). For each subject admitted to the Drug Detoxification and Treatment Center his (her) status on each of the 13 items of CINA were immediately rated. Then, naloxone 0.4 mg was injected iv to precipitate withdrawal symptoms and at 5, 10, 15 min after the naloxone injection, the CINA score of each patient was rated again. The differences among the scores of pre- and post-naloxone injection is a measurement of the degree of withdrawal symptoms. Then, a single dose of DHE was administered sublingually to each patient, all withdrawal symptoms disappeared. These results show that DHE can compete with naloxone for opioid receptors. A good dose-response relationship was found between the 100% suppressive withdrawal sign doses of DHE and the degree of withdrawal sign in heroin addicts. The physical dependence potential of DHE given to heroin addicts sublingually was probably more than that of methadone given to heroin addicts orally by making reference to the report of Dr. Peachy.

Topics: Administration, Sublingual; Adolescent; Adult; Analgesics, Opioid; Etorphine; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Electrocardiography; Fatal Outcome; Heart Failure; Heroin; Heroin Dependence; Humans; Male; Myocardial Infarction; Substance Withdrawal Syndrome

Topics: Adult; Heroin; Heroin Dependence; Humans; Male; Naltrexone; Self Medication; Substance Withdrawal Syndrome

Topics: Adult; Chlorpromazine; Female; Fever; Heroin; Heroin Dependence; Humans; Male; Promethazine; Substance Withdrawal Syndrome; Tachycardia

The effect of relapse to opiate use on blood pressure and heart rate has been studied in heroin-withdrawn addicts treated with clonidine in an outpatient detoxification procedure. The daily dose of clonidine was established according to body weight and amount of heroin usually consumed at the onset of treatment. Patients who returned to heroin use were detected by increased urinary levels of opiates. Clonidine elicited significant reductions of blood pressure and heart rate reaching a plateau in the second day of treatment. Heroin consumption was found to provoke a further decrease of both systolic and diastolic pressure when the time interval between the relapse and the cardiovascular determinations was about 3 h as estimated by the patients. At longer intervals (16 h) this effect was reversed and both the hypotensive and the bradycardiac actions of clonidine seemed to be impaired. The possible impact of endogenous opioids and alpha-2 receptor sensitivity on these biphasic alterations is discussed.

Topics: Adult; Blood Pressure; Clonidine; Dose-Response Relationship, Drug; Female; Heroin; Heroin Dependence; Humans; Male; Recurrence; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Beta endorphin (BE) is a polypeptide agonist for the brain's endogenous opioid system. Levels of BE are elevated by opioid antagonists such as naloxone and depressed by short-acting agonists such as heroin and morphine; they become normalized during steady-state methadone. Buprenorphine (BUP) is a partial opioid agonist whose effects on BE levels were examined in six former heroin addicts and 14 methadone-maintained patients before and after being switched to sublingual BUP 2 mg daily for 1 month. In six former methadone-treated subjects BE levels also were measured after stopping BUP and after naloxone challenge. Levels of BE were not significantly lower in subjects started on BUP after stopping heroin (n = 6) (8.0 versus 8.1 ng/ml) or in subjects started on BUP after stopping methadone (n = 14) (11.6 vs 15.6 ng/ml). However, BE levels were lower on BUP than after naloxone challenge (n = 6) (7.0 versus 34.9 ng/ml). Levels of BE did not significantly change between the first 2 weeks ("early") and "later," although BE levels on methadone significantly correlated with BE levels on BUP in the "early" but not the "later" phase. The BE levels on BUP also did not differ from BE levels of unmedicated normals.

Topics: Adult; beta-Endorphin; Buprenorphine; Female; Heroin; Humans; Male; Methadone; Middle Aged; Naloxone; Radioimmunoassay; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Humans; Methadone; Patient Compliance; Substance Withdrawal Syndrome

Residents in a detoxification/motivation program for drug users provided speech samples just after detoxification and again 5 weeks later. Content analysis scales were used to obtain scores for Hostility (Inward, Outward, and Ambivalent), Cognitive Anxiety, Pawn, Origin, and Sociality. Comparisons were made with scores from a previous sample of students, unemployed people, and drug users. At the end of the program there were significant positive changes in all scores except those for Hostility Outward and Pawn. Of particular interest was the anger expressed just after detoxification and maintained at a significantly high level during the following weeks. This suggests a need for drug-treatment programs to include specific anger-management interventions.

Topics: Adaptation, Psychological; Adolescent; Adult; Anger; Anxiety Disorders; Depressive Disorder; Female; Heroin; Heroin Dependence; Hospital Units; Humans; Interview, Psychological; Male; New South Wales; Substance Withdrawal Syndrome

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

A major problem in treating opiate addiction is relapse within a few months after withdrawal. Learning models of relapse offer some promise toward understanding this problem. The present pilot study examines whether cue-exposure treatment to drug-related cues, in hospital and real life, might reduce relapse. Fourteen opiate addicts were withdrawn on clonidine over 6 days, and 10 of those were exposed to drug-related cues in hospital for 1 week and in real life for another. There were then followed as outpatients up to 6 months. Craving was elicited in half of the 10 patients exposed to drug cues who showed within- and between-session habituation. Four cases were opiate-free at 6 months follow up and 1 at 3 months. Half of the cases had relapsed to heroin at various times up to 6 months. Habituation to craving responses was not obviously related to outcome whereas vocational factors were. The operational use of craving in research is discussed.

Topics: Adult; Cues; Desensitization, Psychologic; Female; Follow-Up Studies; Heroin; Heroin Dependence; Hospitalization; Humans; Male; Recurrence; Risk Factors; Social Environment; Substance Withdrawal Syndrome

Clinical and epidemiological features of intravenous drug addicts (IVDA), who attended the emergency department between 1984 and 1988, were studied. The number of cases treated over these 4 years had increased three-fold (256 vs 724). The median age had increased by 3 years (p less than 0.01). The sex ratio had not changed. A third of the cases knew that they were HIV-seropositive in 1988. The main reason for consultation in 1984 was overdosage and in 1988 it was fever. The rate of admission was similar in both years (around 21%). There was a significant increase in admissions caused by respiratory diseases in 1988 (p less than 0.0001) and a significant decrease of admissions caused by overdosage (p less than 0.001).

Topics: Age Factors; Chi-Square Distribution; Drug Overdose; Emergencies; Emergency Service, Hospital; Heroin; Heroin Dependence; HIV Seropositivity; Humans; Retrospective Studies; Sex Factors; Spain; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

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

A 28-year old Japanese man with heroin abuse was reported. He is an ex-beautician and has abused a variety of substances such as toluene, marihuana, methamphetamine, LSD, and so on since he was in a junior high school in Japan. He experienced an intravenous injection of heroin for five days on his first trip to Thailand in 1989. Soon after he returned home, he went back there to use heroin again. He also experienced tearing and running nose as withdrawal at the end of his ten-day trip. During his third stay there he got a job as a wholesale dealer of heroin under a illegal drug organization in the northern part of Thailand. Before he returned home in Japan, he managed to withdraw from heroin by reducing the dose and replacing it with opium smoking. On his fourth trip he failed to withdraw from heroin and injected the drug intravenously at Chiang Mai Airport before leaving Thailand. He began to show acute heroin withdrawal just after he arrived in Osaka, Japan and sought treatment without telling heroin abuse. He was hospitalized next day and soon showed more severe withdrawal and delirium for next ten days. The delirium was thought to be due to not only heroin but the other drugs which he used. Recently heroin abuse, once prevalent during the latter half of 1950s in Japan, has been hardly seen owing to changing the law to severe punishment in 1963. To avoid strict regulations in home some of young Japanese seem to travel abroad and abuse drugs in Asian countries where the drugs are easily available.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Asia; Heroin; Humans; Male; Substance Withdrawal Syndrome; Substance-Related Disorders; Travel

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

Topics: Administration, Inhalation; Amphetamine; Cocaine; Heroin; Humans; Methadone; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Time Factors

Twelve heroin addicts and one methadone addicts began withdrawal from street opiates, under clonidine cover, in a general psychiatric ward. Ten (80%) of them completed it within 6 days. Clonidine doses used were lower than in similar studies and all patients were alert and mobile throughout withdrawal. Two other groups of opiate addicts, of similar age and sex, were withdrawn on standard methadone regimens. Clonidine and methadone withdrawal had similar acceptability and attrition rates. Self-reports of subjective discomfort were higher in the clonidine group without affecting compliance with treatment. Withdrawal under clonidine cover deserves further study, in view of the need for postwithdrawal treatment to prevent relapse to opiate use.

Topics: Adult; Clonidine; Drug Administration Schedule; Female; Heroin; Heroin Dependence; Hospitalization; Humans; Male; Methadone; Neuropsychological Tests; Substance Withdrawal Syndrome

In previous studies a 32-item Opiate Withdrawal Scale was found to provide a reliable and valid means of measuring the signs and symptoms of withdrawal among heroin (and other opiate) addicts. This paper describes the processes whereby a shorter 10-item version of the same scale was developed. The Short Opiate Withdrawal Scale (SOWS) is simple to understand and easy to administer, and it avoids the redundancy of items contained in the original scale. It is suggested that the SOWS provide a useful instrument which can be used both in research and clinical practice with opiate addicts.

Topics: Heroin; Heroin Dependence; Humans; Neurologic Examination; Psychometrics; Substance Withdrawal Syndrome

Topics: Adult; Antisocial Personality Disorder; Diagnosis, Differential; Heroin; Humans; Male; Malingering; Military Personnel; Stress Disorders, Post-Traumatic; Substance Withdrawal Syndrome

The purpose of this open, uncontrolled study in a group of confirmed heroin addicts of both sexes was to determine whether clonidine by itself suppresses opiate withdrawal reactions, its maximal effective dosage range, the time of maximal effect, duration of its effectiveness and the extent of cardiovascular side effects. After a washout phase of opium residues, clonidine was administered for eight days and its effects were closely monitored and recorded. Even during the first 24 hour period, when clonidine was administered alone in a high dosage, it suppressed the signs and symptoms of opiate withdrawal reactions. The maximum effect was attained within three days. Thereafter, it maintained improvement until natural resolution of the reactions. Side effects were limited to some small but statistically significant cardiovascular changes. Illicit drug use during the treatment period indicated that drug related behaviour is only slightly affected by clonidine. The drug is thus effective in the acute withdrawal phase but does not replace the important psychosocial management needed to achieve long term drug abstinence.

Topics: Arousal; Clonidine; Dose-Response Relationship, Drug; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Neurologic Examination; Patient Compliance; Referral and Consultation; Substance Withdrawal Syndrome

Topics: Clonidine; Heroin; Humans; Naltrexone; Substance Withdrawal Syndrome

Questionnaire measures relating to a recent episode of unmodified heroin withdrawal (the target episode) were obtained from 70 subjects. The duration of the target episode, but not reported distress during the episode, correlated with the amount of heroin consumed in the previous 3 months. Data from scales measuring motivation during the target episode were factor analysed and two factors emerged, one relating to motivation concerning private affairs and the other relating to motivation derived from public sources. High scores for private affairs motivation were correlated with success in the target episode whilst there was a trend for public affairs based motivation to be associated with failure. Private affairs motivation was negatively correlated with length of heroin use but positively correlated with the number of coping strategies employed in withdrawal. The implications of these findings for the treatment of heroin users are discussed.

Topics: Adaptation, Psychological; Adolescent; Adult; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Motivation; Substance Withdrawal Syndrome

While cocaine is now used much more frequently than heroin by women of childbearing age, we have found that a significant number of mothers have abused both drugs during their pregnancy. We studied 86 infants who were born to women with a history of cocaine and/or heroin use during pregnancy. The newborns were observed over a 5-day hospital period using a standardized abstinence scoring system and urine drug screening of both mother and infant. Of these, 35 had maternal and/or newborn urine test results that were positive for cocaine only (cocaine group), 14 that were positive for heroin only (heroin group), 17 that were positive for both cocaine and heroin (cocaine/heroin group), and 20 that were negative for both, although the mothers admitted to cocaine use during their pregnancy (cocaine history group). In approximately half of the mother/infant pairs, the results of the urine drug tests were discordant. Microcephaly and growth retardation occurred most frequently in the infants in the cocaine group (17% and 27%, respectively). Microcephaly was also found to be significant in the infants in the cocaine/heroin group. Signs of drug withdrawal occurred in all four drug-exposed groups. Mild withdrawal occurred in 26% of infants in the cocaine group, 21% of the infants in the heroin group, 47% of the infants in the cocaine/heroin group, and in 30% of the infants in the cocaine history group. Withdrawal requiring treatment occurred in 6% of the infants in the cocaine group, 14% of the infants in the heroin group, 35% of infants in the cocaine/heroin group, and 5% of the infants in the cocaine history group. The use of heroin with cocaine has a synergistic effect on the behavior of the newborn.

Topics: Cocaine; Drug Synergism; Female; Fetal Growth Retardation; Heroin; Humans; Infant, Newborn; Microcephaly; Obstetric Labor, Premature; Phenobarbital; Pregnancy; Prenatal Exposure Delayed Effects; Substance Withdrawal Syndrome

Lever-pressing behavior reinforced by intravenous infusion of various concentrations of heroin, and consequent development of physical dependence, were examined in rats. In addition, the influence of opiate dependence, and of its disappearance following withdrawal, on heroin self-administration were investigated. It was found that intravenous self-administration of heroin at 0.03 mg/kg/infusion maintained self-administration behavior without producing physical dependence. Total responses per session decreased with increasing unit dose of heroin, whereas the total amount of drug self-administered was directly related to unit dose. Significantly greater numbers of withdrawal signs and percentage body weight losses in response to naloxone injections were observed following self-administration of heroin at 0.1, 0.3 or 0.6 mg/kg/infusion. Intake of heroin at 0.03 mg/kg/infusion, but not at 0.1, 0.3 or 0.6 mg/kg/infusion, was found to increase significantly in opiate-dependent and postdependent animals. These findings support the previous use of 0.03 mg/kg/infusion as a suitable dose for illustrating the reinforcing effect of heroin without the influence of physical dependence.

Topics: Animals; Behavior, Animal; Dose-Response Relationship, Drug; Heroin; Male; Naloxone; Rats; Self Administration; Substance Withdrawal Syndrome; Substance-Related Disorders

Attempts to repeat in human subjects animal studies in which naloxone stopped withdrawal symptoms after prolonged use of heroin failed. Nevertheless, suggestions for further studies are made, as the subjects' subsequent desire for opiates did seem attenuated.

Topics: Female; Heroin; Humans; Male; Naloxone; Substance Withdrawal Syndrome

Topics: Clonidine; Heroin; Humans; Receptors, Adrenergic, alpha; Substance Withdrawal Syndrome

Topics: Administration, Oral; Adult; Blood Pressure Determination; Clonidine; Drug Therapy, Combination; Female; Heroin; Home Nursing; Humans; Monitoring, Physiologic; Naltrexone; Substance Withdrawal Syndrome; Telephone

The alpha 2-adrenoceptor stimulant, guanfacine, was used to treat, under open conditions, heroin addicts who volunteered to withdraw from heroin usage. Thirty-four addicts (29 males, 5 females) aged 17 to 31 years were treated for 5 to 15 days with varying doses of guanfacine (0.03 up to 1.75 mg daily). Efficacy was determined by the "Opiate Withdrawal Checklist" (OWCL), administered several times during the day, and by the Clinical Global Impression (CGI) scale. All symptom categories of the OWCL, except "sleep disturbances" were equally ameliorated by the treatment. According to the CGI, 88% of the cases were judged as having had a very good or good improvement. Tolerability to the medication was judged as good or very good in 94% of the cases.

Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Dose-Response Relationship, Drug; Female; Guanfacine; Guanidines; Heroin; Heroin Dependence; Humans; Male; Phenylacetates; Pilot Projects; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome

Methadone detoxification procedures are widely accepted as a satisfactory way of withdrawing opiate addicts from drugs. There have, however, been comparatively few empirical studies which have examined the development and course of withdrawal symptoms in opiate addicts in response to such detoxification procedures. This study investigates the opiate withdrawal syndrome in a group of 116 opiate addicts during and subsequent to a gradual oral methadone detoxification programme. Withdrawal symptoms peak at the end of the methadone schedule and decline steadily thereafter. Not until 40 days after the beginning of the withdrawal regime have symptom levels returned to normal. It is suggested that this protracted withdrawal response is not entirely satisfactory and alternative clinical and research options are proposed. The results fail to support the accepted view that dose is a major determinant of withdrawal severity. Low dose users did not experience less severe withdrawal symptoms than high dose users. This finding together with those of a previous study suggest that this issue also warrants further research attention.

Topics: Adult; Female; Heroin; Humans; Male; Methadone; Substance Withdrawal Syndrome; Time Factors

Maternal, perinatal and neonatal factors of 27 newborns of heroin addicted mothers were reviewed between 1980 and 1984. Results were compared with a control group of 2,587 normal newborns. A progressive increase in number of cases was observed in the last years. Mean age of heroin-addicted mothers was significant lower than control group (p less than 0.001). Only 18.5% were under obstetrical control for at least 4 times (p less than 0.001) and 40.7% had antecedents previous abortions (p less than 0.025). Four cases of maternal syphilis were diagnosed and also four mother were positive to HBsAg; statistical difference in both cases was highly significant with respect to control group (p less than 0.001). A higher index of premature rupture of membranes (11.1%, p less than 0.001) and cesarean sections (25.9%, p less than 0.001) was appreciated. No significant difference was observed attending to fetal presentation, instrumental delivery, Apgar test scores and pH of umbilical artery (p greater than 0.05). A higher incidence of preterm (18.5%, p less than 0.01) and small for gestational age babies (44.4%, p less than 0.001) was ascertained. Pregnancy control and no smoking habit might influence birth weight (p less than 0.001). Neonatal withdrawal syndrome was present in 44.4% and was related to mother's last dose and secondary to degree of heroin abuse (p less than 0.025).

Topics: Birth Weight; Female; Gestational Age; Hepatitis B; Heroin; Heroin Dependence; Humans; Infant, Newborn; Male; Maternal Age; Pregnancy; Pregnancy Complications; Prenatal Care; Substance Withdrawal Syndrome; Syphilis Serodiagnosis

Clonidine hydrochloride (an alpha-2 adrenergic agonist) and naltrexone hydrochloride (an opioid antagonist), given in combination, provided a safe and effective treatment of abrupt opioid withdrawal over 5 days in an outpatient/day setting. Before starting the clonidine, a naloxone challenge test was used to verify and quantify opioid dependence, and the naloxone challenge test score was then used to determine initial medication doses. Initial naloxone challenge test scores predicted subsequent patient discomfort during the 5-day clonidine-naltrexone protocol. Twelve of 14 (86%) heroin users successfully withdrew from opioids and simultaneously initiated naltrexone maintenance.

Topics: Adult; Ambulatory Care; Clonidine; Drug Therapy, Combination; Female; Heroin; Humans; Male; Naltrexone; Substance Withdrawal Syndrome

In 31 patients with tranquilizer-and 13 patients with drug abuse the character and extent of changes in EEG during withdrawal period were studied and the influence of additional abuse of alcohol or barbiturates was investigated. The EEG showed pathological results in 22 patients (50%). Generalised spike activity was dominant, which was found more often in patients with tranquilizer abuse (35%) than in patients with drug abuse (15%). In patients with abuse of tranquilizers and additional alcoholism pathological EEGs were found more often (65%) than in the remaining patients (36%). Also in patients with additional abuse of barbiturates pathological EEGs (67%) were found more often. In patients with drug abuse with or without additional abuse of alcohol or barbiturates there was no difference between the number of normal and pathological EEGs. In patients with longer persistence of the tranquilizer abuse the number of pathological EEGs increased. Controls of the EEG revealed with increasing time interval an increasing number of normalised EEGs especially in patients without alcoholism of barbiturate abuse. Therefore the EEG revealed functional disturbances in the withdrawal period after abuse of tranquilizers or drugs which were more pronounced in patients with additional abuse or alcohol or barbiturates.

Topics: Adolescent; Adult; Aged; Barbiturates; Brain; Cannabis; Electroencephalography; Ethanol; Heroin; Humans; Middle Aged; Substance Withdrawal Syndrome; Tranquilizing Agents

Topics: Clonidine; Heroin; Hospitalization; Humans; Naltrexone; Substance Withdrawal Syndrome

The effect of maternal abuse of heroin on newborn babies was studied in 25 babies born during 1982-6 to 23 heroin users, most of whom smoked the drug. Nineteen of the babies developed withdrawal symptoms, which in 12 were severe enough to require treatment. Five babies were born prematurely; 17 were adequately grown for their gestational age. Four mothers successfully established breast feeding. Twenty two infants were discharged from the hospital into their mother's care with support from the family and community services; at the end of the study only six were living in families in which the parents were married or had a stable relationship. Withdrawal symptoms were short lasting and often self limiting, and no evidence of adverse effect on postnatal growth and development was found. Unstable social circumstances with changes in family dynamics made follow up difficult. Further assessment needs to be carried out to investigate the long term effect of maternal heroin abuse on children.

Topics: Adolescent; Adult; Female; Heroin; Humans; Infant, Newborn; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Dextropropoxyphene; Heroin; Humans; Methadone; Substance Withdrawal Syndrome

Topics: Adult; Female; Fetal Growth Retardation; Heroin; Heroin Dependence; Humans; Methadone; Pregnancy; Pregnancy Complications; Risk; Smoking; Socioeconomic Factors; Substance Withdrawal Syndrome

Topics: Anti-Anxiety Agents; Benzodiazepines; Drug Utilization; Heroin; Humans; Italy; Narcotic Antagonists; Self Medication; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Heroin; Heroin Dependence; Humans; Methadone; Naloxone; Psychotropic Drugs; Substance Withdrawal Syndrome

Intravenous self-administration of heroin was studied in experimentally naive rats, as compared to this behavior in animals rendered tolerant to heroin by multiple injections. The tolerant rats also exhibited mild signs of spontaneous and naloxone-precipitated heroin withdrawal. Self-administration behavior developed earlier in the tolerant rats. In heroin-naive rats, oxytocin treatment did not influence the acquisition of heroin self-administration behavior. In the tolerant rats, on the other hand, oxytocin decreased the acquisition of heroin self-administration. When maintenance of heroin self-administration was studied in the tolerant rats, graded doses of oxytocin (0.05, 0.5 and 5 micrograms s.c.) decreased heroin intake. This finding, which is in agreement with previous data indicating that oxytocin attenuates the development of tolerance to and dependence on narcotic analgesics, suggests that the neuropeptide reduced the reinforcing efficacy of heroin in the tolerant organism.

Topics: Animals; Dose-Response Relationship, Drug; Drug Tolerance; Heroin; Humans; Male; Naloxone; Oxytocin; Rats; Rats, Inbred Strains; Self Administration; Substance Withdrawal Syndrome

Topics: Adult; Child Behavior Disorders; Child Development; Child, Preschool; Female; Follow-Up Studies; Heroin; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Pregnancy; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Heroin; Heroin Dependence; Humans; Naloxone; Substance Withdrawal Syndrome

The effectiveness of beta-endorphin, dynorphin-(1-13), dynorphin-(1-10) amide, alpha-neoendorphin and [D-Ala2,D-Leu5]enkephalin in suppressing withdrawal in heroin addicts was compared in this study. Groups of six patients were stabilized overnight in the hospital and were treated with either saline or peptide when withdrawal symptoms began to appear the following morning. Withdrawal was scored before and after treatment by the patient himself and an independent observer. Peptides were administered in a bolus dose of 60 micrograms/kg body weight. The patient, the observer and the physician who administered the injection were all blind to the nature of the compound given. All treatments, including those with saline, produced an overall reduction of withdrawal score. However, by statistical analysis, only treatments with beta-endorphin, [D-Ala2,D-Leu5]enkephalin and dynorphin-(1-13) were effective in producing a significant decrease of withdrawal symptoms. The length of relief brought about by the different peptides varied from less than an hour to a maximum of 5 h in one case. The average period of relief brought about by beta-endorphin, dynorphin-(1-13) and [D-Ala2,D-Leu5]enkephalin was 44, 46 and 60 min, respectively. Of the five peptides administered [D-Ala2,D-Leu5]enkephalin produced the largest number of side-effects.

Topics: Adult; Animals; beta-Endorphin; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Heroin; Humans; Male; Mice; Peptide Fragments; Protein Precursors; Substance Withdrawal Syndrome

This paper examines a unique finding from a larger research study of methadone maintenance treatment at four treatment programs in three Northeastern states. In looking at methods used by narcotics addicts to withdraw or detoxify from heroin, we found a small group of persons who had successfully detoxified from heroin addiction using a structured injection regimen of gradually decreasing amounts of heroin and gradually increasing amounts of cocaine. While this paper represents the case study of ten cases, the regimen was reported by others as part of 'street pharmacology.' It is a relatively uncommon regimen, reportedly due to the expense of the procedure and the problems associated with cocaine abuse. It is the pharmacological aspects of the procedure which warrant attention. All ten cases reported little or no withdrawal symptoms after the last injection containing small amounts of heroin. It was widely believed that cocaine interacts with heroin in a way which masks withdrawal during the detoxification process, providing a measure of physiological relief. Information from the addict world on that interaction provides clues as to the biochemical properties of drug interactions and may suggest areas for further clinical and pharmacological research.

Topics: Adult; Cocaine; Drug Interactions; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Methadone; Self Medication; Substance Withdrawal Syndrome

The hypothesis for this therapeutic use of delta sleep-inducing peptide (DSIP) was based on several animal studies conducted by Tissot. He showed that morphine, alcohol, pentobarbital as well as DSIP, when injected directly into the bulbo-mesencephalo-thalamic recruiting system, induced slow-wave sleep with numerous spindles. In all cases, this effect was reversed by Naloxone. Thus, it has been postulated that DSIP possesses an agonistic activity on opiate receptors and might be of value in the treatment of withdrawal syndromes. Therefore, DSIP was administered intravenously to 107 inpatients presenting with symptoms of alcohol (n = 47) or opiate (n = 60) withdrawal. The assessment of effect was based on the clinical evaluation by the physician and the nursing staff. Approximately 13% of the patients from the first and 22% from the second group did not fulfil the requirements for the evaluation of treatment. In, respectively, 97 and 87% of opiate and alcohol addicts, the clinical symptoms and signs disappeared after DSIP administration or improved markedly and rapidly. Anxiety, however, was slower to decrease. On the average, the clinical symptomatology had a more prolonged course and a higher number of DSIP injections were required for opiate addicts than for alcoholics. Tolerance to the DSIP treatment was good, aside from headaches reported by a few patients.

Topics: Adult; Delta Sleep-Inducing Peptide; Ethanol; Female; Heroin; Humans; Injections, Intravenous; Male; Methadone; Middle Aged; Narcotics; Oligopeptides; Pentazocine; Substance Withdrawal Syndrome

Description of a case of benign acute transverse myelopathy in a young woman who had taken heroin I.V. after a two-year free interval. Spinal angiography was negative but CT scanning of the cord showed a swelling at C3.

Topics: Acute Disease; Adult; Drug Hypersensitivity; Female; Heroin; Humans; Hypesthesia; Injections, Intravenous; Paraplegia; Spinal Cord Diseases; Substance Withdrawal Syndrome

A new syndrome of acquired immunodeficiency has been identified in seven children who were small for gestational age at birth and subsequently have exhibited failure to thrive, lymphadenopathy, parotitis, hepatosplenomegaly, interstitial pneumonia, and recurrent infections. All have a profound cell-mediated immunodeficiency with reversed T4/T8 ratios. Six are hypergammaglobulinemic and one has low IgG levels. The mothers of five of the seven children are sexually promiscuous and/or drug addicts. Three mothers have an immunodeficiency similar to that found in their infants. One of them died at age 33 years with a diagnosis of acquired immunodeficiency syndrome. In five of the children and in three of their mothers, there is evidence of a persistent Epstein-Barr virus (EBV) infection. We speculate that a perinatal or in utero transmission of EBV can induce an "infectious immunodeficiency." The clinical, histopathologic, and immunologic features resemble those described in adult homosexuals and drug addicts.

Topics: Acquired Immunodeficiency Syndrome; Age Factors; Child, Preschool; Female; Heroin; Humans; Infant; Male; Maternal-Fetal Exchange; Pregnancy; Prenatal Exposure Delayed Effects; Sexual Behavior; Substance Withdrawal Syndrome; Substance-Related Disorders; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: Ambulatory Care; Heroin; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders

On the basis of current literature and their own experience, the authors discuss (1) the major complications possible in pregnant drug addicts, (2) whether the complications can be attributed to deficient prenatal care or to effects of drug abuse, and (3) the best prenatal care of drug-addicted mothers.

Topics: Birth Weight; Delivery, Obstetric; Female; Fetal Monitoring; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Infant Mortality; Infant, Newborn; Methadone; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prenatal Care; Substance Withdrawal Syndrome

In an open study of 50 patients with heroin addiction, clonidine was efficacious by mouth in the treatment of acute heroin-withdrawal syndrome. Mean administration of clonidine (on an "as-needed" basis) was 5 days (maximum 7 days), whilst the mean daily dosage ranged from 0.112 mg to 0.468 mg, the maximum requirement occurring on day 2 of withdrawal and sinking thereafter. Since insomnia was not influenced by clonidine, we offered 100 mg doxepine and/or 10 mg nitrazepam (the latter only until day 4 of treatment). Under this medication a sudden, dramatic decrease in blood pressure was not seen, mean blood pressure and pulse rate were not markedly altered; this may, perhaps, be a consequence of the blocking effect of doxepine on the peripheral hypotensive actions of clonidine. Of the 9 drop-outs from treatment, five (10% of the total 50) were certainly directly attributable to the lack of response to clonidine, representing a failure of therapy in 10% cases at least.

Topics: 2-Hydroxyphenethylamine; Clonidine; Dose-Response Relationship, Drug; Doxepin; Drug Administration Schedule; Heroin; Humans; Nitrazepam; Octopamine; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Vertigo

Topics: Clonidine; Heroin; Humans; Narcotics; Substance Withdrawal Syndrome

A group of 13 babies born to heroin-addict mothers has been studied in our Department during the last three years. Authors have recorded clinical features like neonatal abstinence syndrome, malformations, intrauterine growth, maternal age, gestational duration and delivery. They discuss different types of malformations and withdrawal symptoms, and make a comparative study with normal newborns of our hospital.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Female; Fetal Growth Retardation; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

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: Adolescent; Adult; Cesarean Section; Female; Heroin; Humans; Infant, Newborn; Ireland; Male; Maternal-Fetal Exchange; Methadone; Pregnancy; Pregnancy Complications; Prenatal Care; Smoking; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

Experimental data are presented in support of the hypothesis on the role of positive and negative reinforcing systems in the mechanism of drug dependence. Drugs with abuse potential (DAP) may change the manner of response to negative emotional stimuli, activate positive emotional reactions in animals, and possess primary reinforcing properties. Reward and punishment systems respond sensitively to withdrawal from DAP or antagonist administration. Catecholaminergic and peptidergic processes are of importance in the mechanisms of the emotionally positive action of DAP.

Topics: Amphetamines; Animals; Cats; Chlordiazepoxide; Cocaine; Diazepam; Drug Tolerance; Escape Reaction; Ethanol; Heroin; Humans; Morphine; Pentobarbital; Psychophysiology; Rats; Reinforcement, Psychology; Substance Withdrawal Syndrome; Substance-Related Disorders

This paper describes the range of experience of 28 heroin addicts who received LAAM instead of methadone over six weeks in an outpatient detoxification program. Four patients are singled out to illustrate the variety of response during withdrawal, temporary abstinence from drugs, and social adjustment. The paper explores the motivation of patients and both their physical and subjective responses to the detoxification attempt. By describing a variety of patients, the paper documents clinical responses that cannot be communicated in statistical summaries or single-case reports. Overall, the cases illustrate the difficulties of brief-stay outpatient detoxification from heroin. Clinicians should expect to see only small steps toward rehabilitation during a patient's attempt to taper from opiates, but even minimal progress may justify the use of detoxification programs as a link between "street life" and the decision to enter long-term treatment.

Topics: Adult; Heroin; Heroin Dependence; Humans; Male; Methadone; Methadyl Acetate; Patient Dropouts; Social Adjustment; Substance Withdrawal Syndrome

Topics: Adult; Apnea; Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lysergic Acid Diethylamide; Morphine; Pentazocine; Pregnancy; Pregnancy Complications; Respiration, Artificial; Substance Withdrawal Syndrome; Substance-Related Disorders

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

Topics: Animals; Association; Conditioning, Classical; Cues; Drug Tolerance; Extinction, Psychological; Heroin; Humans; Morphine; Rats; Recurrence; Substance Withdrawal Syndrome; Substance-Related Disorders

Blood pressure and plasma renin activity were studied in 13 infants of drug-dependent mothers (heroin and/or methadone) and 20 control newborns for a period of 21 days. Urinary excretion of epinephrine and norepinephrine were also measured at 24 and 48 h of age. The systolic blood pressure was found to be significantly elevated in newborns of drug-dependent mothers compared with controls (p less than 0.01), but diastolic blood pressure levels were similar. Plasma renin activity was significantly elevated (p less than 0.001) at 48-72 h and urinary epinephrine levels were significantly lower (p less than 0.05) at 24-48 h of age in the drug group, and norepinephrine levels were equivalent. Systolic hypertension and elevated plasma renin activity in these newborns of dependent mothers may be due to increased beta-adrenergic receptor sensitivity.

Topics: Catecholamines; Diastole; Female; Heroin; Humans; Hypertension; Infant, Newborn; Infant, Newborn, Diseases; Male; Methadone; Pregnancy; Receptors, Adrenergic, beta; Renin; Substance Withdrawal Syndrome; Systole

The scarce or absent analgesic effect exhibited by morphine on pain from migraine attack and the poor inhibition of the spasmogenic effect of 5-HT (tested on the hand dorsal vein, computerized venotest) suggest the hypothesis of an opioid receptor deficiency in headache sufferers. Since endogenous opioids control the nociception, the sense of well being, and the vegetative balance, an opioid receptoral hypofunction could be the background of the headache and central panalgia, where the trinity pain, anhedonia, and dysautonomia are the characteristic features.

Topics: Animals; Haplorhini; Headache; Heroin; Humans; Migraine Disorders; Pain; Receptors, Opioid; Substance Withdrawal Syndrome

Topics: Drug-Related Side Effects and Adverse Reactions; Heroin; Humans; Illicit Drugs; Morphine; Substance Withdrawal Syndrome

This study investigated the effect of acute heroin withdrawal on the pattern of sleep--waking state sequences. Subjects included drug-dependent patients using pure heroin and drug-free controls. Electrophysiological data were recorded on a 24-hour per day basis for the first 5 - 7 days of withdrawal. EEG records were scored according to standard criteria. Marked increases in the sequential state changes occurred during withdrawal when progressing from awake-with-alpha, stage I, stage II and rapid eye movement (REM) sleep to the awake state. Heroin withdrawal also caused significant decreases in sequential state changes when proceeding from waking or light sleep states into deeper sleep states or into REM sleep. This study revealed that heroin withdrawal caused more abrupt transitions from quiet awake or sleeping conditions into the awake state and impeded progression into slow wave or REM sleep states.

Topics: Alpha Rhythm; Electroencephalography; Heroin; Humans; Sleep Stages; Sleep, REM; Substance Withdrawal Syndrome; Wakefulness

Management of 50 experimental newborn infants ill with narcotic withdrawal has been carried out with the aid of an instrument developed for measuring its severity, the Neonatal Narcotic Withdrawal Index (NNWI). With its use, infants exposed to methadone in utero have been successfully cared for with detoxification needed in less than 25% of cases and for durations of less than 2 weeks. The percentage of cases and the length of treatment is much less than is customary for infants who have been prenatally exposed to similar doses of methadone. Validity of the NNWI is shown by the statistically significant difference between the mean scores for experimental and control subjects, a high significant correlation between simultaneously measured scores by separate examiners, statistically significant correlations between subscores and total withdrawal scores for the narcotic-exposed experimental cases, and for this group, a statistically significant correlation between scores of withdrawal and the maternal dose of methadone. The simplicity of the NNWI should help to make it acceptable for use by physicians.

Topics: Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Opium; Pregnancy; Psychological Tests; Substance Withdrawal Syndrome

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 study was to evaluate the effects of acute heroin withdrawal on waking behavior and slow wave sleep. Data were collected from drug-dependent patients who were using pure heroin and from drug-free controls. All data were recorded on a 24-hour per day basis for 5 - 7 consecutive days. EEG records were manually scored according to standard criteria. The heroin-dependent patients during withdrawal showed approximately a 26% decrease in slow wave sleep and an 18% increase in waking behavior. The awake state in the heroin-dependent patients during withdrawal also displayed an increase in number of episodes and number of state shifts, and a decrease in duration and sleep onset latency. In addition, the slow wave sleep categories during withdrawal generally showed an increase in sleep onset latency and interstate interval and a decrease in number of episodes. These results indicate that heroin withdrawal is associated with a marked disruption of the central nervous system mechanisms responsible for maintenance of the normal sleep--waking cycle. Analyses of the pattern of this disruption will further aid in understanding the withdrawal syndrome.

Topics: Electroencephalography; Heroin; Humans; Sleep; Substance Withdrawal Syndrome; Wakefulness

The purpose of this study was to examine overt behavioral characteristics and sleep during acute heroin abstinence in man. Both heroine-dependent patients and drug-free control subjects were observed and monitored on a 24-hour per day basis for 5 to 7 days. Observational data were analyzed for frequency of occurrence of various behaviors including the signs and symptoms of withdrawal. Electroencephalographic (EEG) data were scored into awake and sleep stages according to standard techniques. The heroin-dependent subjects generally displayed a higher number of observations across all recording days as compared to the controls. In addition, the signs and symptoms of withdrawal for these patients peaked on day 1 or day 2 and then declined over the remaining recording days. The EEG state data showed an increase in waking and decrease in both slow wave and REM sleep during acute heroin withdrawal. Total sleep was maximally suppressed on withdrawal days 2 and 3 and was still below normal control values on withdrawal days 5 - 7. REM sleep was more disrupted than slow-wave sleep during withdrawal from heroin. Results of this study indicate that heroin withdrawal produces a differential action upon central nervous system structures responsible for the various states of sleep, waking and related behaviors.

Topics: Acute Disease; Electroencephalography; Ethanol; Heroin; Humans; Sleep; Sleep Stages; Substance Withdrawal Syndrome; Wakefulness

Heroin addicts on 0 or 2 mg of methadone and finishing a 14-day detoxification program, and control subjects were shown a videotape of heroin-related stimuli. Psychological questionnaires were completed before and after the videotape, while physiological responses were monitored during viewing. It was found that the experimental subjects had an increased level of anxiety, depression, and subjective level of craving following the stimulus presentation, with the controls showing no similar change in these measures. In addition, the experimental group had significant increases in heart rate and galvanic skin response compared with controls. The results present some of the first objective evidence of conditioned abstinence occurring in addicts exposed to stimuli closely related to those found in the natural environment.

Topics: Conditioning, Psychological; Heroin; Heroin Dependence; Humans; Respiration; Substance Withdrawal Syndrome; Videotape Recording

Topics: Heroin; Humans; Substance Withdrawal Syndrome

Complex zinc tannate salts of heroin, hydromorphone and l-alpha-acetylmethadol were synthesized and injected in a slow-release vehicle, into rats. One, 3, 7, 10 and 14 days after the drug was administered rats were injected with naloxone hydrochloride (10 mg/kg) and during the following 4 hours body weights, core temperature and behavioral signs such as diarrhea, writhing, teeth chattering and wet dog shakes were recorded. On every naloxone testing day the narcotic-treated groups presented behavioral signs of abstinence, but weight loss and temperature changes were much less consistent. Reduction of core temperature following naloxone administration seems to be an earlier indicator of physical dependence than weight loss. According to the parameters tested a level of physical dependence can persist for at least two weeks after a single injection of these narcotic salts.

Topics: Animals; Behavior, Animal; Body Temperature; Body Weight; Heroin; Heroin Dependence; Humans; Hydromorphone; Methadone; Methadyl Acetate; Naloxone; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adaptation, Psychological; Anxiety; Heroin; Heroin Dependence; Humans; Methadone; Phobic Disorders; Relaxation Therapy; Substance Withdrawal Syndrome; Token Economy

Topics: Ataxia; Coma; Depression; Electroencephalography; Female; Heroin; Heroin Dependence; Humans; Male; Mental Disorders; Muscular Diseases; Myelitis, Transverse; Nervous System Diseases; Neuritis; Neurocognitive Disorders; Nystagmus, Pathologic; Parkinson Disease, Secondary; Sexual Dysfunction, Physiological; Sleep Wake Disorders; Substance Withdrawal Syndrome; Tremor

Topics: Female; Fetus; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Labor, Obstetric; Methadone; Postpartum Period; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

Indirect evidence has linked opioid reinforcement with changes in noradrenergic metabolism secondary to drug administration. Methodological precedents for biobehavioral correlations in depressive illness have suggested an important association between changes in mood and biogenic amine excretion patterns in the urines of patients during depression and recovery. This paper presents preliminary data on the possible relationship between changes in catecholamine excretion that were observed and the changes in behavior, mood, psychiatric status, and cardiorespiratory physiology secondary to heroin administration and methadone-assisted withdrawal. This study focuses on the urinary excretion of MHPG, since an appreciable fraction of this metabolite is probably derived from norepinephrine originating in the brain. The subjective changes in mood associated with heroin use, the decrease in respiratory rate, and the behavioral and mental status effects associated with opiate intoxication were observed only in the individuals whose MHPG excretion increased during the period of opiate administration.

Topics: Adult; Behavior; Catecholamines; Emotions; Heroin; Humans; Male; Methadone; Methoxyhydroxyphenylglycol; Narcotics; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome

Mice were given single s.c. injections of morphine sulphate (M.S.), heroin hydrochloride (H.HCl) and the sparingly-soluble diheroin pamoate (H.Pam) and 3,5-di-tert-butyl-2,6-dihydroxybenzoate (H.Bnz) in three vehicles, saline, peanut oil, or a slow-release vehicle (SRV) and tested for analgesia by both the tail-clip and hotplate techniques. Duration of analgesia as assessed by the tail-clip method was always longer than that by the hotplate when equivalent doses were used in any vehicle. The H.Pam and H.Bnz salts significantly prolonged the analgesia: the mean duration in mice injected with equivalent amounts of heroin base was 3.0 hr for the group receiving heroin HCl in saline and 7.8 hr after H.Bnz in slow-release vehicle. An inverse relationship was evident between the degree of dissociation of H from the three salts, at pH 7.3 and their durations of analgesia in vivo. This was statistically significant (p less than 0.01) at the higher dose level. All mice were challenged with naloxone hydrochloride (1 mg/kg) 24 hr after the injection of each narcotic agonist preparation. The jumping behaviour elicited by naloxone was not consistently related to dose, salt form, or vehicle employed for the injection of agonists, but from 12.5 too 54.2% of all the mice did jump at that time. The durations of analgesia observed and the intensity of the jumping response correlated significantly with the mean number of jumps per mouse after the naloxone challenge.

Topics: Analgesia; Animals; Delayed-Action Preparations; Guinea Pigs; Heroin; Heroin Dependence; Humans; Male; Morphine; Morphine Dependence; Naloxone; Reaction Time; Substance Withdrawal Syndrome; Time Factors

A case of poor intrauterine fetal growth is reported, observed during the pregnancy of a 16 years old heroin addicted primigravida. Near on term she was delivered of an almost mature male liveborn of only 37 cm and 1300 g. Our results of placental function-tests with reference to otherwise reported effects of maternal heroin addiction are discussed.

Topics: Adolescent; Female; Fetal Growth Retardation; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal-Fetal Exchange; Placenta Diseases; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

Topics: Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

Topics: Animals; Choice Behavior; Decision Making; Food; Haplorhini; Heroin; Humans; Male; Morphine; Papio; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome

Topics: Dextropropoxyphene; Drug Tolerance; Heroin; Heroin Dependence; Humans; Methadone; Morphine; Morphine Dependence; Naloxone; Substance Withdrawal Syndrome

32 pregnancies in 29 drug-addicted women were studied ouver eight years in one obstetric department working in close liaison with a drug dependency centre. Of the 24 pregnancies which came to term, only 10 were seen at the antenatal clinic before 22 weeks' gestation. 19 of the women were addicted to heroin or methadone or a mixture of both, 4 were taking soft drugs, and 1 was taking pethidine only. Labour commenced spontaneously in 17 pregnancies and was induced in 7. All labours lasted less than twenty hours. 23 infants survived. Those born to the mother taking pethidine and to 4 mothers who withdrew their drug of dependence four weeks before delivery showed no signs of narcotic withdrawal, but 13 out of 14 infants born to mothers taking heroin or methadone developed narcotic withdrawal syndrome. It is recommended that drug therapy during pregnancy in addicts should be supervised by a psychiatrist known to the patient and that oral methadone be substituted for heroin. Planned induction will ensure delivery in hospital, at the hospital which has supervised the pregnancy. Babies in danger of developing narcotic withdrawal syndrome should be observed in the special care baby unit for the first week of life.

Topics: Adult; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Labor, Obstetric; London; Methadone; Postpartum Period; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Adult male rats receiving 5 or 20 mg/kg heroin HCl by single injections (08:00 or 20:00 hr) or in 3 equal injections (8 hr intervals) showed a disruption in the normal diurnal pattern of behavior. Initially, heroin abolished feeding for several hr after the injection, reduced the total daily food consumption in a dose-related manner, due primarily to decreased night-time feeding, and prevented or slowed weight gain. Subsequent heroin injections led to a phase of vigorous feeding following the period of depression. Magnitude and duration of the depression decreased, but the stimulatory phase of feeding became more pronounced as tolerance developed. Total daily food intake and body weight returned towards control levels, but the proportion eaten during daylight hr became elevated. Sporadic feeding occurred on the first withdrawal day with abolition of the stimulatory phase which had followed each heroin injection. Subsequently, the normal diurnal pattern of behavior gradually returned. Close measurement of 24 hr food consumption may be a sensitive and valuable measure of the disruptive effects of narcotic analgesics.

Topics: Animals; Circadian Rhythm; Drug Tolerance; Feeding Behavior; Heroin; Humans; Male; Rats; Substance Withdrawal Syndrome; Time Factors

Effects of in vitro methadone and several other narcotics were investigated on 3H-5-HT uptake in rat hypothalamus slices. The results indicated that d, l-methadone and levorphanol had slightly greater inhibitory action on the uptake than the isomers, d-methadone and dextrorphan, respectively. Morphine, diacetylmorphine and the narcotic antagonist naloxone produced a considerably weaker inhibitory effect. After an acute injection of methadone, but not morphine, the uptake of 5-HT by hypothalamic slices of treated animals was inhibited. The chronic treatment of rats with methadone for 18 days had no significant effect on the uptake, but following the withdrawal of this treatment for 2 weeks the 5-HT uptake was significantly elevated. The inhibitory effects of in vitro methadone in the hypothalamus slices were not modified by the chronic drug treatment.

Topics: Animals; Dextrorphan; Female; Heroin; Humans; Hypothalamus; In Vitro Techniques; Levorphanol; Methadone; Morphine; Naloxone; Rats; Serotonin; Substance Withdrawal Syndrome; Time Factors

Narcotic addicts may become so conditioned to the use of hypodermic needles that self-injection without a drug may become pleasurable. This phenomenon has raised the question as to whether addicts in treatment should be administered any medication by hypodermic needle for fear of precipitating withdrawal or inducing a craving for heroin. In this study addicts in treatment were given a medicinal needle challenge but there were no documented deleterious effects.

Topics: Conditioning, Operant; Heroin; Heroin Dependence; Humans; Injections, Subcutaneous; Morphine; Needles; Substance Withdrawal Syndrome

Topics: Adult; Drug Tolerance; Heroin; Heroin Dependence; Humans; Male; Methadone; Methadyl Acetate; Middle Aged; Narcotics; Substance Withdrawal Syndrome; Time Factors

Rectral temperatures and feeding activity were measured in adult male rats every 30 min for 4 hr, then every 4 hr following daily s.c. injections at 08:00 or 20:00hr or saline or heroin. Initial heroin injections disrupted diurnal temperature and feeding rhythms: 5 mg/kg heroin HCl induced hyperthermia and abolished feeding for 2 hr; 20 mg/kg led to hypothermia, then hyperthermia and abolished feeding for 4 hr. By the 5th heroin day hyperthermia and increased feeding occurred in all groups with a shorter latency to onset. Total food intake was higher than on the 1st heroin day but the diurnal patterns remained disrupted. Changes in both diurnal rhythms again occurred on the 1st withdrawal day as hypothermia, sporadic feeding and hyper-irritability were observed. By the 5th withdrawal day diurnal temperature and feeding rhythms resembled those of the control period. Monitoring diurnal temperature and feeding patterns of rats reveals characteristic dose-related disruptions after heroin which are modified by repeated doses as tolerance develops and which eventually disappear on withdrawal.

Topics: Animals; Behavior, Animal; Body Temperature; Circadian Rhythm; Drug Tolerance; Feeding Behavior; Heroin; Humans; Male; Motor Activity; Rats; Substance Withdrawal Syndrome; Time Factors

A case of a severe heroin withdrawal syndrom in a newborn infant is reported. Diagnostic and therapeutic aspects of the disease are reviewed.

Topics: Chloral Hydrate; Diazepam; Female; Heroin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Muscle Tonus; Phenobarbital; Pregnancy; Seizures; Substance Withdrawal Syndrome

Topics: Adult; Female; Heroin; Humans; Nalorphine; Substance Withdrawal Syndrome; Ventricular Fibrillation

Opiate-dependent patients who are hospitalized for medical, surgical, or obstetrical reasons require proper management of their addiction to care of their presenting illness. Guidelines are offered for methadone support during hospitalization for the patient enrolled in a treatment program and for the street addict. The important clinical features of withdrawal reactions are outlined, and a method is presented for establishing an initial and supportive dose of methadone for street addicts. The use of analgesics in the addicted patient, the treatment of methadone overdose, and some problems in the management of mixed-drug abuse are discussed.

Topics: Analgesia; Drug Administration Schedule; Drug Combinations; Drug Interactions; Female; Heroin; Hospitalization; Humans; Legislation, Drug; Male; Methadone; Morphine; Physician-Patient Relations; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

From all US Army enlistees leaving Vietnam in September 1971, a random sample of 943 men was selected. Of these, 470 represented a "general" sample of all enlistees returning at that time, and 495 represented a "drug positive" sample whose urine samples had been positive for opiates at the time of departure. We attempted to locate and personally interview all of the men in the samples. Results indicate that before arrival, hard drug use was largely casual, and less than 1% had ever been addicted to narcotics. In Vietnam, almost half of the general sample tried narcotics and 20% reported opiate addiction. After return, usage and addiction essentially decreased to pre-Vietnam levels. We discuss the use of nonnarcotic drugs, predictors and correlates of drug use in the samples, and the relationship of drugs to post-Vietnam social adjustment.

Topics: Age Factors; Alcohol Drinking; Amphetamine; Barbiturates; Cannabis; Heroin; Humans; Injections, Intravenous; Male; Military Psychiatry; Narcotics; Opium; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; United States; Veterans; Vietnam

Narcotic addicts self-administered heroin intravenously for 10 days under controlled research ward conditions and were subsequently detoxified with methadone for 7 days. Plasma testosterone levels decreased signifcantly when heroin dosage was between 45 and 65 mg/day contrasted to predrug base-line levels. Testosterone levels remained depressed during methadone withdrawal. No statistically significant changes in a.m. plasma cortisol levels were observed during both heroin acquisition and methadone withdrawal.

Topics: Adult; Heroin; Heroin Dependence; Humans; Hydrocortisone; Male; Methadone; Substance Withdrawal Syndrome; Testosterone; Time Factors

The behavior of narcotics-addicted and nonaddicted newborns on the first 2 days of life was assessed with the Brazelton Neonatal Behavioral Assessment Scale. In addition to classic signs of narcotics abstinence, addicted infants were less able to be maintained in an alert state and less able to orient to auditory and visual stimuli. These deficits were especially pronounced at 48 hours of age. Addicted infants were as capable of self-quieting and responding to soothing intervention as normal neonates, although they were substantially more irritable. These characteristics and addicted infants' greater resistance to cuddling are discussed in terms of their potential impact on early infant-care-giver interaction.

Topics: Adult; Attention; Female; Habituation, Psychophysiologic; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Labor, Obstetric; Male; Maternal-Fetal Exchange; Methadone; Orientation; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders

The effects on behaviour and growth of rats given heroin s.c. every 8-hr, and during withdrawal (saline q.8.h.) were studied. Performance of rats trained on one food-reinforcement schedule (FR-10 or VI-10) was tested every day after one of the injections of saline or heroin. Doses of 0.25 mg/kg/injection heroin hydrochloride were increased stepwise to 32 mg/kg as "behavioural tolerance" developed. Threshold doses which blocked feeding in the first 30 min of testing ranged from 0.75 to 4.0 mg/kg and "tolerance" to 32 mg/kg/injection required from 18-71 + days. Heroin interrupted growth in heavier rats; lighter rats gained like saline-treated controls. Within 48 hr of withdrawal bar-pressing increased but all rats lost weight, were hyperirritable, and had diarrhoea. Thereafter, performance and body weight rose steadily. Administration of heroin at regular intervals over a prolonged period, and withdrawal from it, cause a disruption in behaviour comparable to that reported for morphine.

Topics: Animals; Body Weight; Conditioning, Operant; Depression, Chemical; Drug Tolerance; Heroin; Humans; Male; Rats; Reinforcement Schedule; Stimulation, Chemical; Substance Withdrawal Syndrome; Time Factors

Topics: Apgar Score; Birth Weight; Breech Presentation; Chlorpromazine; Delivery, Obstetric; Female; Fetal Death; Hepatitis; Hernia, Inguinal; Heroin; Heroin Dependence; Humans; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Jaundice, Neonatal; Menstruation Disturbances; Pregnancy; Pregnancy Complications; Prenatal Care; Substance Withdrawal Syndrome; United States

Topics: 5-Hydroxytryptophan; Animals; Behavior, Animal; Delayed-Action Preparations; Disease Models, Animal; Drug Synergism; Heroin; Humans; Male; Morphine; Morphine Dependence; Motor Activity; Naloxone; Rats; Substance Withdrawal Syndrome; Theophylline

Topics: Abnormalities, Drug-Induced; Adult; Age Factors; Barbiturates; Camphor; Chlorpromazine; Codeine; Diazepam; Female; Fetus; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal Age; Methadone; Opium; Phenobarbital; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Circadian Rhythm; Constriction; Dilatation; Heroin; Heroin Dependence; Humans; Male; Pupil; Reflex, Pupillary; Substance Withdrawal Syndrome; United States; Vietnam

Topics: Amphetamine; Antipsychotic Agents; Barbiturates; Cannabis; Child Welfare; Chlorpromazine; Diazepam; Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lysergic Acid Diethylamide; Maternal-Fetal Exchange; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Analgesics; California; Community Health Services; Counseling; Heroin; Heroin Dependence; Humans; Hypnotics and Sedatives; Methadone; Social Problems; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Alcohol Drinking; Alcoholism; Disulfiram; Heroin; Heroin Dependence; Hospitalization; Humans; Methadone; Reinforcement, Psychology; Social Adjustment; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Attitude; Black or African American; Death; Depression; District of Columbia; Female; Heroin; Heroin Dependence; Humans; Interview, Psychological; Male; Methadone; Personality Inventory; Racial Groups; Substance Withdrawal Syndrome; Substance-Related Disorders; Suicide; Violence

Topics: Adolescent; Adult; Alcoholism; Child; Criminal Psychology; Ethnicity; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Life Style; Male; Methadone; Middle Aged; New Mexico; Prisons; Social Adjustment; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Evaluation Studies as Topic; Female; Heroin; Heroin Dependence; Humans; Interpersonal Relations; Male; Methadone; Personality Inventory; Psychoanalytic Theory; Psychotherapy, Group; Sensitivity Training Groups; Student Health Services; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Attitude; Communication; Competitive Behavior; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Physician-Patient Relations; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

Topics: Barbiturates; Dose-Response Relationship, Drug; Drug Tolerance; Female; Heroin; Humans; Hypnotics and Sedatives; Methadone; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Drug Tolerance; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Methadone; Nalorphine; Opium; Rehabilitation Centers; Socioenvironmental Therapy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Abnormalities, Drug-Induced; Adult; Birth Weight; Female; Fetal Death; Fetus; Gestational Age; Heroin; Humans; Infant Mortality; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Endocarditis, Bacterial; Heroin; Heroin Dependence; Humans; Naloxone; Substance Withdrawal Syndrome; Substance-Related Disorders; Tetanus

Topics: Adult; Heroin; Heroin Dependence; Humans; Male; Methadone; Prisoners; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Anxiety; Crime; Heroin; Heroin Dependence; Humans; Legislation as Topic; Methadone; Motivation; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; United States

Topics: Adolescent; Adult; Age Factors; Aged; Black or African American; Black People; Cannabis; Crime; Female; Heroin; Heroin Dependence; Humans; Legislation, Drug; Male; Methadone; Methods; Middle Aged; Opium; Sex Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom; United States; White People

Topics: Adult; Asia, Southeastern; Environmental Exposure; Heroin; Heroin Dependence; Humans; Male; Military Medicine; Military Personnel; Motivation; Peer Group; Social Adjustment; Stress, Physiological; Stress, Psychological; Substance Withdrawal Syndrome; Substance-Related Disorders; United States; Warfare

Topics: Adolescent; Adult; Counseling; Ethnicity; Female; Heroin; Heroin Dependence; Humans; Legislation, Drug; Male; Methadone; Michigan; Psychosocial Deprivation; Quality of Health Care; Rehabilitation Centers; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; United States; United States Food and Drug Administration

Topics: Administration, Oral; Adult; Apgar Score; Birth Weight; Female; Fetal Death; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Methadone; New York City; Obstetric Labor, Premature; Parity; Pregnancy; Pregnancy Complications; Prognosis; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Acetates; Administration, Oral; Adult; Amino Alcohols; Delayed-Action Preparations; Dimethylamines; Dose-Response Relationship, Drug; Drug Tolerance; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Middle Aged; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Adult; Eye Diseases; Heroin; Humans; Male; Military Personnel; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders; United States; Vietnam

Topics: Adult; Birth Weight; Depression; Female; Fetal Diseases; Fetus; Heroin; Heroin Dependence; Humans; Hyperbilirubinemia; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Microsomes, Liver; Narcotics; Pregnancy; Respiratory Distress Syndrome, Newborn; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Atropine; Behavior, Animal; Drug Interactions; Fenclonine; Heroin; Humans; Indomethacin; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Morphine; Motor Activity; Naloxone; Phenylalanine; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome; Time Factors

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adolescent; Adrenocorticotropic Hormone; Adult; Age Factors; Birth Weight; Dexamethasone; Estriol; Female; Heroin; Humans; Infant, Newborn; Methadone; Metyrapone; Parity; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Anxiety; Compulsive Behavior; Conditioning, Classical; Conditioning, Operant; Dogs; Drug Tolerance; Haplorhini; Heroin; Humans; Life Style; Methadone; Mice; Morphine Dependence; Motivation; Narcotic Antagonists; Rats; Recurrence; Reward; Substance Withdrawal Syndrome; Time Factors

Topics: Adolescent; Adult; Alcoholism; Female; Geography; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Nutritional Physiological Phenomena; Substance Withdrawal Syndrome; Substance-Related Disorders; Weather

Topics: Adult; Age Factors; Alcoholism; Black or African American; Community Mental Health Services; Educational Status; Evaluation Studies as Topic; Female; Heroin; Hospitalization; Humans; Length of Stay; Male; Massachusetts; Methadone; Methods; Religion; Substance Withdrawal Syndrome; Substance-Related Disorders; White People

Topics: Costs and Cost Analysis; Criminal Psychology; Drug Tolerance; Evaluation Studies as Topic; Heroin; Humans; Methadone; Morphine Dependence; Recurrence; Remission, Spontaneous; Social Problems; Stress, Psychological; Substance Withdrawal Syndrome

Topics: Breath Tests; Coma; False Negative Reactions; False Positive Reactions; Heroin; Humans; Medical History Taking; Methods; Nalorphine; Pharmaceutical Preparations; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Anticonvulsants; Apgar Score; Barbiturates; Epilepsy; Female; Gestational Age; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Phenobarbital; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Adult; Cardiac Surgical Procedures; Curettage; Dextropropoxyphene; Dilatation; Female; Fracture Fixation; Heroin; Humans; Hysterectomy; Male; Meperidine; Methadone; Orthopedics; Pain; Pentazocine; Substance Withdrawal Syndrome; Substance-Related Disorders; Surgery, Oral; Surgical Procedures, Operative

Topics: Adult; Female; Heroin; Hospitalization; Humans; Male; Methadone; Psychotherapy; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Group Processes; Health Education; Heroin; Humans; Male; Military Medicine; Morphine Dependence; Personality; Social Behavior; Social Environment; Substance Withdrawal Syndrome; United States; Vietnam; Warfare

Topics: Acid-Base Equilibrium; Alkalosis, Respiratory; Capillaries; Carbon Dioxide; Heroin; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Infant, Newborn, Diseases; Respiration; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Amniocentesis; Bilirubin; Birth Weight; Female; Gestational Age; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Pregnancy; Pregnancy Complications; Prenatal Care; Psychotherapy, Group; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Acetylcholine; Birth Weight; Central Nervous System; Epinephrine; Female; Gestational Age; Heroin; Humans; Infant, Newborn; Infant, Premature, Diseases; Nicotine; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders; Sweat Glands; Sweating

Topics: Adolescent; Adult; Calcium; Gluconates; Heroin; Humans; Injections, Intravenous; Male; Pain; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Administration, Oral; Adult; Constipation; Erectile Dysfunction; Evaluation Studies as Topic; Female; Heroin; Hospitalization; Humans; Male; Methadone; Middle Aged; Morphine Dependence; Narcotics; Psychotherapy; Recurrence; Social Adjustment; Substance Withdrawal Syndrome; Sweating

Topics: Adult; California; Community Mental Health Services; Female; Heroin; Hospitalization; Hospitals, Teaching; Humans; Internship and Residency; Length of Stay; Male; Methadone; Morphine Dependence; Psychiatric Department, Hospital; Psychiatry; Referral and Consultation; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Amphetamine; California; Cannabis; Child; Community Health Services; Female; Heroin; Humans; Male; Medical Records; Methadone; Middle Aged; Morphine Dependence; Self Medication; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Dosage Forms; Drug Prescriptions; Drug Utilization; England; Heroin; Humans; Legislation, Drug; Methadone; Morphine Dependence; Seasons; Substance Withdrawal Syndrome

Topics: Administration, Oral; Adolescent; Adult; Ambulatory Care; Amobarbital; Barbiturates; Community Health Services; Female; Heroin; House Calls; Humans; Injections, Intramuscular; Male; Morphine Dependence; Pentobarbital; Phenobarbital; Secobarbital; Substance Withdrawal Syndrome; Substance-Related Disorders; Volunteers

Topics: Female; Gestational Age; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal-Fetal Exchange; Methadone; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Alcohol Drinking; Alcoholism; Cannabis; Delayed-Action Preparations; Disulfiram; Heroin; Humans; Methadone; Morphine Dependence; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Barbiturates; Female; Heroin; Hospitalization; Humans; Male; Meperidine; Methadone; Morphine; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Tranquilizing Agents

Topics: Administration, Oral; Adolescent; Heroin; Humans; Injections, Intravenous; Male; Methadone; New York City; Prisons; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Animals; Heroin; Humans; Injections, Intravenous; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Female; Gestational Age; Heroin; Humans; Male; Methadone; Morphine Dependence; Pregnancy; Substance Withdrawal Syndrome

Topics: Adult; Criminal Psychology; Employment; Evaluation Studies as Topic; Follow-Up Studies; Heroin; Hospitalization; Humans; Methadone; Morphine Dependence; Remission, Spontaneous; Substance Withdrawal Syndrome; United States; Voluntary Health Agencies

Topics: Costs and Cost Analysis; Economics, Medical; Heroin; Hospitalization; Humans; Length of Stay; Methadone; Probability; Substance Withdrawal Syndrome; Substance-Related Disorders; Therapeutic Community; United Kingdom; United States

Topics: Adolescent; Adult; Antidotes; Cannabis; Female; Hallucinogens; Heroin; Humans; Lysergic Acid Diethylamide; Male; Mescaline; Morphine; Morphine Dependence; Poisoning; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Heroin; Humans; Israel; Methadone; Opium; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amenorrhea; Child Abuse; Child Rearing; Female; Heroin; Heroin Dependence; Humans; Libido; Physician-Patient Relations; Pregnancy; Pregnancy Complications; Psychiatry; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Birth Weight; Child Development; Child Welfare; Chlorpromazine; Heroin; Heroin Dependence; Humans; Infant, Newborn; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Atropine; Chlormethiazole; Cyanides; Drug Combinations; Evaluation Studies as Topic; Female; Gastrointestinal Agents; Heroin; Humans; Isonipecotic Acids; Male; Meperidine; Narcotics; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Bilirubin; Diazepam; Endoplasmic Reticulum; Female; Glucuronates; Heroin; Hexosyltransferases; Humans; Infant, Newborn; Jaundice, Neonatal; Liver; Male; Maternal-Fetal Exchange; Microscopy, Electron; Morphine; Morphine Dependence; Pregnancy; Protein Binding; Rats; Serum Albumin; Substance Withdrawal Syndrome

Topics: Acute Disease; Birth Weight; Carbon Dioxide; Enzyme Induction; Female; Gestational Age; Heroin; Humans; Infant, Newborn; Obstetric Labor, Premature; Partial Pressure; Pregnancy; Respiratory Distress Syndrome, Newborn; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Methadone; Morphine Dependence; Pregnancy; Substance Withdrawal Syndrome

Topics: Heroin; Humans; Male; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Apgar Score; Birth Weight; Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Methadone; Neurologic Manifestations; Opium; Phenobarbital; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders; Vomiting

Topics: Canada; Crime; Drug and Narcotic Control; Heroin; Humans; Methadone; Organization and Administration; Social Problems; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; United States

Topics: Adult; Heroin; Humans; Male; Methadone; Substance Withdrawal Syndrome; Substance-Related Disorders

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs. Sydney E. Salmon and Robert W. Schrier, Assistant Professors of Medicine, under the direction of Dr. Lloyd H. Smith, Jr., Professor of Medicine and Chairman of the Department of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, San Francisco, Ca. 94122.

Topics: Bacterial Infections; Chemical and Drug Induced Liver Injury; Endocarditis, Bacterial; Heroin; Humans; Lung Diseases; Malaria; Substance Withdrawal Syndrome; Substance-Related Disorders; Tetanus

Topics: Adult; Cholangitis; Cholecystitis; Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Methadone; Morphine Dependence; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

Topics: Canada; Drug and Narcotic Control; Heroin; Humans; Methadone; Methods; Societies, Medical; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Alcohol Drinking; Criminal Psychology; Evaluation Studies as Topic; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Jurisprudence; Male; Methadone; Middle Aged; Remission, Spontaneous; Social Adjustment; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: American Medical Association; Female; Health Education; Heroin; Humans; Legislation, Drug; Methadone; Morphinans; Morphine; Morphine Dependence; Pain; Personality; Pregnancy; Pregnancy Complications; Socioeconomic Factors; Substance Withdrawal Syndrome; United States

Topics: Barbiturates; Hepatitis B; Heroin; Humans; Morphine; Nutrition Disorders; Opium; Respiratory Tract Infections; Sexually Transmitted Diseases; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Birth Weight; Chlorpromazine; Congenital Abnormalities; Female; Heroin; Humans; Infant, Newborn; Jaundice, Neonatal; Magnesium; Male; Maternal-Fetal Exchange; Morphine; Pregnancy; Quinine; Sleep; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Analysis of Variance; Chromatography, Thin Layer; Colorimetry; Electroencephalography; Electrooculography; Heroin; Humans; Male; Methods; Morphine; Sleep; Sleep Stages; Sleep, REM; Substance Withdrawal Syndrome

Topics: Amphetamine; Barbiturates; Cannabis; Central Nervous System; Cocaine; Ethanol; Hallucinogens; Heroin; Humans; Morphine; Nicotine; Pharmacology; Substance Withdrawal Syndrome; Substance-Related Disorders; Synaptic Transmission

Topics: Bibliographies as Topic; Heroin; Humans; Methadone; Morphine Dependence; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Chlormethiazole; Cocaine; Female; Heroin; Humans; Isonipecotic Acids; Male; Methadone; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Amphetamine; Barbiturates; Cannabis; Female; Heroin; Humans; Infant, Newborn; Lysergic Acid Diethylamide; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Chlorpromazine; Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Morphine Dependence; Phenobarbital; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Age Factors; Criminal Psychology; Female; Heroin; Humans; Male; New York City; Social Conditions; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Acute Kidney Injury; Administration, Oral; Adolescent; Alkaline Phosphatase; Amenorrhea; Amphetamine; Barbiturates; Cannabis; Child; Cocaine; Eosinophilia; False Positive Reactions; Female; Hepatic Encephalopathy; Hepatitis B; Heroin; Humans; Injections, Intravenous; Injections, Subcutaneous; Juvenile Delinquency; Lysergic Acid Diethylamide; Peptic Ulcer; Pneumonia; Pseudotumor Cerebri; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Barbiturates; Chlordiazepoxide; Diazepam; Heroin; Humans; Meprobamate; Pentobarbital; Phenobarbital; Phenytoin; Secobarbital; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Amphetamine; Barbiturates; Drug Interactions; Female; Glutethimide; Heroin; Humans; Lysergic Acid Diethylamide; Male; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Heroin; Humans; Methadone; Substance Withdrawal Syndrome; Wit and Humor as Topic

Topics: Amphetamine; Animals; Barbiturates; Brain; Cannabis; Central Nervous System; Cocaine; Drug Tolerance; Guinea Pigs; Heroin; Humans; Hypothalamus; Ileum; Lysergic Acid Diethylamide; Morphine; Morphine Dependence; Nerve Endings; Opium; Psychoses, Substance-Induced; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Ambulatory Care; Community Mental Health Services; Evaluation Studies as Topic; Female; Heroin; History, 16th Century; Humans; Illinois; Male; Methadone; Morphine Dependence; Substance Withdrawal Syndrome

Topics: Adult; Ambulatory Care; Community Mental Health Services; Female; Financing, Organized; Heroin; Hospitals, General; Hospitals, Teaching; Humans; Male; Methadone; Minnesota; Morphine Dependence; Outpatient Clinics, Hospital; Private Practice; Psychotherapy; Substance Withdrawal Syndrome

Topics: Adult; Chromatography, Thin Layer; Community Mental Health Services; Counseling; Heroin; Hospitalization; Humans; Male; Methadone; Missouri; Morphine Dependence; Outpatient Clinics, Hospital; Professional-Patient Relations; Substance Withdrawal Syndrome

Topics: Adult; Aged; Ambulatory Care; British Columbia; Community Mental Health Services; Crime; Criminal Psychology; Employment; Evaluation Studies as Topic; Female; Heroin; Humans; Male; Methadone; Middle Aged; Morphine Dependence; Prisons; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Community Mental Health Services; Crime; Drug Prescriptions; Emergency Service, Hospital; Evaluation Studies as Topic; Fees and Charges; Female; Financing, Personal; Florida; Heroin; Humans; Male; Methadone; Morphine Dependence; Substance Withdrawal Syndrome; Volunteers

Topics: Analgesics; Azocines; Cyclazocine; Evaluation Studies as Topic; Heroin; Hospitalization; Hospitals, General; Hospitals, Teaching; Humans; Methadone; Morphinans; Morphine Dependence; Naloxone; Narcotic Antagonists; Narcotics; New York City; Outpatient Clinics, Hospital; Psychotherapy; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Aged; British Columbia; Community Health Services; Criminal Psychology; Employment; Evaluation Studies as Topic; Female; Heroin; Humans; Male; Methadone; Middle Aged; Morphine Dependence; Outpatient Clinics, Hospital; Social Behavior; Substance Withdrawal Syndrome

Topics: Adolescent; Diabetes Complications; Diabetic Ketoacidosis; Heroin; Humans; Male; Substance Withdrawal Syndrome

Topics: Anxiety Disorders; Chronic Disease; Depression; Euphoria; Heroin; Humans; Hypnotics and Sedatives; Hypochondriasis; MMPI; Morphine; Morphine Dependence; Neurasthenia; Personality; Personality Disorders; Personality Inventory; Substance Withdrawal Syndrome

Topics: Amphetamine; Barbiturates; Condiments; Drug Synergism; Hallucinations; Hallucinogens; Hepatitis A; Heroin; Humans; Lung Diseases; Lysergic Acid Diethylamide; Mental Disorders; Petroleum; Psychomotor Disorders; Psychoses, Substance-Induced; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Aged; Ejaculation; Heroin; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Nalorphine; Opium; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Vomiting

Topics: Adult; Heroin; Humans; Morphine Dependence; Substance Withdrawal Syndrome

Topics: Adult; Heroin; Humans; Male; Pentobarbital; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Community Health Services; Heroin; Humans; Methadone; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom

Topics: Adult; Age Factors; Barbiturates; Drug and Narcotic Control; Drug Synergism; Female; Heroin; Humans; Income; Male; Motivation; Sex Factors; Social Problems; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Attitude of Health Personnel; England; Heroin; Humans; Parent-Child Relations; Personality; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Barbiturates; Cannabis; Drug and Narcotic Control; Female; Heroin; Humans; Legislation, Drug; Male; Methadone; Morphine; Nalorphine; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Drug Tolerance; Follow-Up Studies; Heroin; Humans; Hydromorphone; Injections, Intravenous; Methadone; Morphine; Rehabilitation; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Euphoria; Heroin; Humans; Hydromorphone; Methadone; Morphine; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Barbiturates; Female; Heroin; Humans; Male; Morphine Dependence; New York City; Opium; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Cocaine; Female; Heroin; Humans; Hypnotics and Sedatives; Male; Meperidine; Substance Withdrawal Syndrome; Substance-Related Disorders; Thiazoles

Topics: Chronic Disease; Heroin; Humans; Methadone; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Drug Therapy; Drug Tolerance; Heroin; Humans; Methadone; Substance Withdrawal Syndrome; Substance-Related Disorders; Toxicology

Topics: Adolescent; Cocaine; Cocaine-Related Disorders; Heroin; Humans; Psychotherapy; Psychotherapy, Group; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Amphetamine; Barbiturates; Cannabis; Cocaine; Dextroamphetamine; Ethanol; Female; Follow-Up Studies; Heroin; Hospitalization; Hospitals, Psychiatric; Humans; Injections, Intravenous; Male; Methadone; Morphine; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom; United States

Topics: Adult; Heroin; Humans; Methadone; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Heroin; Humans; Morphine; Smoking; Substance Withdrawal Syndrome; Substance-Related Disorders; Thiazoles

Topics: Chloral Hydrate; Chlorpromazine; Drug Therapy; Glutethimide; Heroin; Humans; Meprobamate; Methylphenidate; New York; Substance Withdrawal Syndrome; Substance-Related Disorders; Toxicology

Topics: Aminopyrine; Animals; Aspirin; Atropine; Behavior, Animal; Codeine; Heroin; Histamine H1 Antagonists; Humans; Lysergic Acid Diethylamide; Morphine; Morphine Dependence; Noscapine; Rats; Substance Withdrawal Syndrome

Topics: Adolescent; Female; Heroin; Heroin Dependence; Humans; Male; Substance Withdrawal Syndrome; Substance-Related Disorders