buprenorphine and Cocaine-Related-Disorders

Substance use disorders (SUD) are serious public health problems worldwide. Although significant progress has been made in understanding the neurobiology of drug reward and the transition to addiction, effective pharmacotherapies for SUD remain limited and a majority of drug users relapse even after a period of treatment. The United States Food and Drug Administration (FDA) has approved several medications for opioid, nicotine, and alcohol use disorders, whereas none are approved for the treatment of cocaine or other psychostimulant use disorders. The medications approved by the FDA for the treatment of SUD can be divided into two major classes - agonist replacement therapies, such as methadone and buprenorphine for opioid use disorders (OUD), nicotine replacement therapy (NRT) and varenicline for nicotine use disorders (NUD), and antagonist therapies, such as naloxone for opioid overdose and naltrexone for promoting abstinence. In the present review, we primarily focus on the pharmacological rationale of agonist replacement strategies in treatment of opioid dependence, and the potential translation of this rationale to new therapies for cocaine use disorders. We begin by describing the neural mechanisms underlying opioid reward, followed by preclinical and clinical findings supporting the utility of agonist therapies in the treatment of OUD. We then discuss recent progress of agonist therapies for cocaine use disorders based on lessons learned from methadone and buprenorphine. We contend that future studies should identify agonist pharmacotherapies that can facilitate abstinence in patients who are motivated to quit their illicit drug use. Focusing on those that are able to achieve abstinence from cocaine will provide a platform to broaden the effectiveness of medication and psychosocial treatment strategies for this underserved population. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.

Topics: Analgesics, Opioid; Buprenorphine; Central Nervous System Stimulants; Cocaine-Related Disorders; Dextroamphetamine; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Drug Development; Humans; Methadone; Methylphenidate; Modafinil; Nicotinic Agonists; Opiate Substitution Treatment; Opioid-Related Disorders; Oxalates; Piperazines; Receptors, Opioid, mu; Tobacco Use Disorder; Tropanes; Varenicline

Although counseling is a required part of office-based buprenorphine treatment of opioid use disorders, the nature of what constitutes appropriate counseling is unclear and controversial. The authors review the literature on the role, nature, and intensity of behavioral interventions in office-based buprenorphine treatment.. The authors conducted a review of randomized controlled studies testing the efficacy of adding a behavioral intervention to buprenorphine maintenance treatment.. Four key studies showed no benefit from adding a behavioral intervention to buprenorphine plus medical management, and four studies indicated some benefit for specific behavioral interventions, primarily contingency management. The authors examined the findings from the negative trials in the context of six questions: 1) Is buprenorphine that effective? 2) Is medical management that effective? 3) Are behavioral interventions that ineffective in this population? 4) How has research design affected the results of studies of buprenorphine plus behavioral treatment? 5) What do we know about subgroups of patients who do and those who do not seem to benefit from behavioral interventions? 6) What should clinicians aim for in terms of treatment outcome in buprenorphine maintenance?. High-quality medical management may suffice for some patients, but there are few data regarding the types of individuals for whom medical management is sufficient. Physicians should consider a stepped-care model in which patients may begin with relatively nonintensive treatment, with increased intensity for patients who struggle early in treatment. Finally, with 6-month retention rates seldom exceeding 50% and poor outcomes following dropout, we must explore innovative strategies for enhancing retention in buprenorphine treatment.

Topics: Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Heroin Dependence; Humans; Long-Term Care; Methadone; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Patient Compliance; Patient Preference; Randomized Controlled Trials as Topic

Cocaine use activates the dopamine reward pathway, leading to the reinforcing effects of dopamine. There is no FDA-approved medication for treating cocaine dependence. Opioid agonists and antagonists have been approved for treating opioid and alcohol dependence. Agonists that activate the μ opioid receptor increase dopamine levels in the nucleus accumbens, while μ receptor antagonists decrease dopamine levels by blocking the effects of endogenous opioid peptides. Activation of the κ opioid receptor decreases dopamine levels and leads to dysphoria. In contrast, inhibition of the κ opioid receptor decreases dopamine levels in the nucleus accumbens. Antagonists acting at the κ receptor reduce stress-mediated behaviors and anxiety. Mixed partial μ/κ agonists have the potential of striking a balance between dopamine levels and attenuating relapse to cocaine. The pharmacological properties of mixed μ/κ opioid receptor agonists will be discussed and results from clinical and preclinical studies will be presented. Results from studies with some of the classical benzomorphans and morphinans will be presented as they lay the foundation for structure-activity relationships. Recent results with other partial opioid agonists, including buprenorphine derivatives and the mixed μ/κ peptide CJ-15,208, will be discussed. The behavioral effects of the mixed μ/κ MCL-741, an aminothiazolomorphinan, in attenuating cocaine-induced locomotor activity will be presented. While not a mixed μ/κ opioid, results obtained with GSK1521498, a μ receptor inverse agonist, will be discussed. Preclinical strategies and successes will lay the groundwork for the further development of mixed μ/κ opioid receptor agonists to treat cocaine dependence.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cocaine-Related Disorders; Dose-Response Relationship, Drug; Humans; Methadone; Peptides, Cyclic; Receptors, Opioid, kappa; Receptors, Opioid, mu; Structure-Activity Relationship

To review evidence on the effectiveness of opioid maintenance treatment (OMT) in prison and post-release.. Systematic review of experimental and observational studies of prisoners receiving OMT regarding treatment retention, opioid use, risk behaviours, human immunodeficiency virus (HIV)/hepatitis C virus (HCV) incidence, criminality, re-incarceration and mortality. We searched electronic research databases, specialist journals and the EMCDDA library for relevant studies until January 2011. Review conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.. Twenty-one studies were identified: six experimental and 15 observational. OMT was associated significantly with reduced heroin use, injecting and syringe-sharing in prison if doses were adequate. Pre-release OMT was associated significantly with increased treatment entry and retention after release if arrangements existed to continue treatment. For other outcomes, associations with pre-release OMT were weaker. Four of five studies found post-release reductions in heroin use. Evidence regarding crime and re-incarceration was equivocal. There was insufficient evidence concerning HIV/HCV incidence. There was limited evidence that pre-release OMT reduces post-release mortality. Disruption of OMT continuity, especially due to brief periods of imprisonment, was associated with very significant increases in HCV incidence.. Benefits of prison OMT are similar to those in community settings. OMT presents an opportunity to recruit problem opioid users into treatment, to reduce illicit opioid use and risk behaviours in prison and potentially minimize overdose risks on release. If liaison with community-based programmes exists, prison OMT facilitates continuity of treatment and longer-term benefits can be achieved. For prisoners in OMT before imprisonment, prison OMT provides treatment continuity.

Topics: Buprenorphine; Cocaine-Related Disorders; Continuity of Patient Care; Crime; Epidemiologic Methods; Heroin Dependence; Humans; Illicit Drugs; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Prisoners; Risk-Taking; Treatment Outcome

Cocaine dependence is characterized by compulsive drug seeking and high vulnerability to relapse. Overall, cocaine remains one of the most used illicit drugs in the world. Given the difficulty of achieving sustained recovery, pharmacotherapy of cocaine addiction remains one of the most important clinical challenges. Recent advances in neurobiology, brain imaging and clinical trials suggest that certain medications show promise in the treatment of cocaine addiction. The pharmacotherapeutic approaches for cocaine dependence include medications able to target specific subtypes of dopamine receptors, affect different neurotransmitter systems (i.e. noradrenergic, serotonergic, cholinergic, glutamatergic, GABAergic and opioidergic pathways), and modulate neurological processes. The systematic reviews concerning the pharmacological treatment of cocaine dependence appear to indicate controversial findings and inconclusive results. The aim of future studies should be to identify the effective medications matching the specific needs of patients with specific characteristics, abandoning the strategies extended to the entire population of cocaine dependent patients. In the present review we summarize the current pharmacotherapeutic approaches to the treatment of cocaine dependence with a focus on the new patents.

Topics: Acetylcysteine; Atomoxetine Hydrochloride; Baclofen; Benzhydryl Compounds; Buprenorphine; Cocaine-Related Disorders; Fructose; Humans; Modafinil; Ondansetron; Patents as Topic; Propylamines; Topiramate

This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may herald more significant learning and behavioral problems during school-age and adolescence when the child is inevitably confronted with increasing social and academic challenges is the subject of ongoing longitudinal research.

Topics: Buprenorphine; Child Development; Child, Preschool; Cocaine; Cocaine-Related Disorders; Female; Heroin; Humans; Infant; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Substance-Related Disorders

To determine the efficacy of Opiate Maintenance Therapy (OMT) and adjunctive interventions for dual heroin and cocaine dependence by means of a meta-analysis.. We searched for and retrieved randomized controlled clinical trials. We used RevMan 5.0 with random effects modeling for statistical analysis and for comparisons of relative risk, effect sizes, and confidence intervals. Subsequent moderator variables and sensitivity analyses were performed.. Thirty-seven studies, which have enrolled 3,029 patients, have been included in this meta-analysis. High doses of OMT were more efficacious than lower ones in the achievement of sustained heroin abstinence (RR = 2.24 [1.54, 3.24], p < .0001) but had no effect on cocaine abstinence. At equivalent doses, methadone was more efficacious than buprenorphine on cocaine abstinence (RR = 1.63 [1.20, 2.22], p = .002) and also appeared to be superior on heroin abstinence (RR = 1.39 [1.00, 1.93], p = .05). Several pharmacological and psychological potentiation strategies have been investigated. An improvement on sustained cocaine abstinence was achieved with indirect dopaminergic agonists (RR = 1.44 [1.05, 1.98], p = .03) and with contingency management (CM) focusing on cocaine abstinence (RR = 3.11 [1.80, 5.35], p < .0001).. Dual opioid and cocaine dependence can be effectively treated with OMT in combination with adjunctive interventions. Higher OMT doses are preferable to lower ones and methadone to buprenorphine. OMT can be enhanced with indirect dopaminergic drugs and with CM focusing on cocaine abstinence.

Topics: Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Humans; Methadone; Narcotics; Opioid-Related Disorders; Treatment Outcome

Contingency management (CM) is a strategy that uses positive reinforcement to improve the clinical outcomes of substance abusers in treatment, especially sustained abstinence from drugs of abuse. Further, CM has been adopted to improve methodology and interpretation of outcomes in clinical trials testing new pharmacotherapies and to improve adherence to efficacious medications in substance abuse patients. Thus, CM has proven to be widely useful as a direct therapeutic intervention and as a tool in treatment development.

Topics: Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Humans; Motivation; Naltrexone; Narcotic Antagonists; Patient Compliance; Receptors, Opioid, mu; Reinforcement, Psychology; Reward; Substance Abuse Detection; Substance Abuse Treatment Centers; Substance-Related Disorders; Treatment Outcome

Our objective was to compare the effectiveness of buprenorphine (BUP) and methadone maintenance treatment in opiate-addicted patients in a clinical nonexperimental setting.. We used a naturalistic observational prospective study of 24 months' duration.. Subjects were enrolled and treated at a drug addiction outpatient clinic of the National Health System Local Unit in Milan, Italy.. Two hundred fifty-seven subjects meeting the DSM-IV criteria for opioid dependence and opioid-seeking substitutive pharmacological treatment participated in the study.. One hundred twenty-one subjects received BUP at a mean daily dose of 11 +/- 6 mg (median = 8; range = 2-30) for a mean duration of 249 days. One hundred thirty-six subjects received methadone at a mean daily dose of 54 +/- 29 mg (median = 50; range = 4-140) for a mean duration of 267 days.. The main efficacy parameters were treatment retention rates and illicit substance abuse, as assessed by urinalysis.. Retention rates were comparable in both treatment groups, but BUP-treated subjects had significantly lower rates of illicit opiate consumption (p < .0001).. The results confirm that, in a nonexperimental clinical practice setting, BUP is as effective as methadone in the treatment of heroin dependence, with significantly better opiate abuse control, thus possibly allowing longer and more effective treatment programs with reduced relapse rates.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Male; Methadone; Narcotics; Occupational Therapy; Psychiatric Status Rating Scales; Social Support; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

Despite the effectiveness of drug treatment and harm reduction programmes aimed at reducing illegal drug use, especially heroin use, situations at risk of transmitting HCV infection are still very frequent. Among routes of drug administration, injection appears as the most dangerous mean regarding the spread of HCV infection among drug users. This practice frequently occurs within a context of a group sharing climate (equipment, substance, housing, etc.) and mutual support. Risk of unsafe behaviour is increased at the time of their first injection or during the first steps of their experience as newly injectors. Public health interventions should target a reduction in the number of injections by modifying the pharmacological format of sublingual buprenorphine, by defining the cessation of injection as one of the main objectives of drug users care programs, by designing and implementing interventions and iniatives that target recreational multiple drug users at risk of initiating drug injection.

Topics: Administration, Sublingual; Adolescent; Adult; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Data Collection; Female; France; Hepatitis C; Heroin Dependence; Humans; Incidence; Male; Narcotic Antagonists; Prospective Studies; Public Health; Risk-Taking; Substance Abuse, Intravenous; Substance-Related Disorders; Time Factors

In 1989, the National Institute on Drug Abuse (NIDA) established its Medications Development Program. This program has concentrated on developing pharmacotherapies for opiate and cocaine dependence and, more recently, for methamphetamine and cannabis dependence. The major goals of this program are to optimize existing treatments and to expand treatment options for physicians and patients. This review will concentrate on the development of pharmacotherapies for the following substance abuse disorders: opiate, cocaine, methamphetamine, and cannabis dependence. Left untreated, opiate and stimulant dependence are responsible for significant morbidity and mortality. For example, use of illicit opiates is associated with an increased risk of hepatitis C infection, HIV infection, and other medical consequences, e.g., an overdose. The NIDA Medications Development Program has had success in developing, with pharmaceutical partners, levomethadyl acetate, buprenorphine, and buprenorphine/naloxone for opiate dependence. Moreover, several marketed medications have shown promise in reducing cocaine use. Of interest, these medications likely operate through diverse neurochemical mechanisms, suggesting that combination therapy may be a rational next step that could increase treatment gains further in cocaine-dependent patients. The Medications Development Program has also identified multiple neuronal mechanisms that are altered by chronic administration of drugs of abuse. Advances in neuroscience have identified changes in conditioned cueing, drug priming, stress-induced increases in drug intake, and reduced frontal inhibitory mechanisms as all being possible for the development of, maintenance of, and possible relapse to, addiction. Potential medications that modulate these mechanisms are highlighted.

Topics: Animals; Buprenorphine; Chemistry, Pharmaceutical; Clinical Trials as Topic; Cocaine-Related Disorders; Dopamine; Drug Design; Drug Industry; Drug Therapy, Combination; Humans; Methadyl Acetate; Naloxone; National Institutes of Health (U.S.); Opioid-Related Disorders; Program Development; Secondary Prevention; Substance-Related Disorders; United States

Given the difficulty of achieving sustained recovery, pharmacotherapy of opioid and cocaine addiction is more effective when combined with behavioral and psychosocial approaches. Effective pharmacotherapies for opioid dependence and withdrawal include methadone, L-alpha acetylmethadol (LAAM), naltrexone, buprenorphine, and clonidine. Treatment of cocaine addiction includes anti-craving agents, dopamine agonists or blocking agents, antidepressants, and treatment of co-morbid psychiatric disorders, but all with mixed results. In this paper, we discuss the use of medication in the context of general principles of opioid and cocaine addiction treatment. Both established medications and promising directions in pharmacotherapy will be addressed.

Topics: Buprenorphine; Clonidine; Cocaine-Related Disorders; Comorbidity; Heroin Dependence; Humans; Mental Disorders; Methadone; Methadyl Acetate; Naltrexone; Narcotic Antagonists; Narcotics

The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP).. Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines.. In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response.. These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine; Cocaine-Related Disorders; Delayed-Action Preparations; Enkephalins; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Protein Precursors

This study examined whether starting buprenorphine treatment prior to prison and after release from prison would be associated with better drug treatment outcomes and whether males and females responded differently to the combination of in-prison treatment and post-release service setting.. Study design was a 2 (In-Prison Treatment: Condition: Buprenorphine Treatment: vs. Counseling Only)×2 [Post-Release Service Setting Condition: Opioid Treatment: Program (OTP) vs. Community Health Center (CHC)]×2 (Gender) factorial design. The trial was conducted between September 2008 and July 2012. Follow-up assessments were completed in 2014. Participants were recruited from two Baltimore pre-release prisons (one for men and one for women). Adult pre-release prisoners who were heroin-dependent during the year prior to incarceration were eligible. Post-release assessments were conducted at 1, 3, 6, and 12-month following prison release.. Participants (N=211) in the in-prison treatment condition effect had a higher mean number of days of community buprenorphine treatment compared to the condition in which participants initiated medication after release (P=0.005). However, there were no statistically significant hypothesized effects for the in-prison treatment condition in terms of: days of heroin use and crime, and opioid and cocaine positive urine screening test results (all Ps>0.14) and no statistically significant hypothesized gender effects (all Ps>0.18).. Although initiating buprenorphine treatment in prison compared to after-release was associated with more days receiving buprenorphine treatment in the designated community treatment program during the 12-months post-release assessment, it was not associated with superior outcomes in terms of heroin and cocaine use and criminal behavior.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Counseling; Crime; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prisoners; Recurrence; Sex Characteristics; Treatment Outcome; Young Adult

Disulfiram may be efficacious for treating cocaine dependence or abuse, possibly through inhibiting dopamine β-hydroxylase (DβH). Consequently, this randomized, placebo-controlled clinical trial of disulfiram during buprenorphine maintenance treatment evaluated the study hypothesis that disulfiram is superior to placebo and explored whether disulfiram response is greatest for participants with a single nucleotide polymorphism coding for genetically low DβH (T-allele carriers).. We randomized 177 buprenorphine-treated opioid dependent participants with cocaine dependence or abuse to 12 weeks of double-blind treatment with disulfiram 250mg daily (n=91) or placebo (n=86). Of 155 participants genotyped, 84 were CC-homozygous, and 71 CT or TT genotypes. Primary outcomes included days per week cocaine use, number of cocaine-negative urine tests, and maximum consecutive weeks of cocaine abstinence. We analyzed an intention-to-treat comparison between disulfiram and placebo. We also explored potential pharmacogenetic interactions and examined treatment responses of four participant groups based on medication (disulfiram or placebo) by genotype (CC-homozygous or T-allele carrier) classification.. Disulfiram participants reported significantly less frequent cocaine use; the differences in cocaine-negative urine tests or consecutive weeks abstinence were not significant. Frequency of cocaine use was lowest in disulfiram-treated T-allele carriers; differences in cocaine-negative urine tests or consecutive weeks abstinence were not significant among the four medication-genotype groups.. The findings provide limited support for the efficacy of disulfiram for reducing cocaine use and suggest that its mechanism of action may involve inhibition of DβH. Further studies of its efficacy, mechanism of action, and pharmacogenetics of response are warranted.

Topics: Adolescent; Adult; Alcohol Deterrents; Alcoholism; Alleles; Buprenorphine; Cocaine-Related Disorders; Data Interpretation, Statistical; Disulfiram; DNA; Double-Blind Method; Drug Therapy, Combination; Female; Genotype; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Pharmacogenetics; Polymerase Chain Reaction; Sample Size; Treatment Outcome; Young Adult

Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans.. Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N=300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors.. Participants assigned to OP received, on average, 3.67 (SD=1.30)h of counseling per active week in treatment. IOP participants received an average of 5.23 (SD=1.68)h of counseling per active week (less than the anticipated 9h per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p=.67) or cocaine dependence (p=.63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps>.05).. Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements.

Topics: Ambulatory Care; Baltimore; Black or African American; Buprenorphine; Cocaine-Related Disorders; Counseling; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders

Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study.. This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates.. This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP.

Topics: Administration, Sublingual; Adolescent; Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome; Young Adult

Cigarette smoking is common among patients in cocaine and opioid dependence treatment, and may influence treatment outcome. We addressed this issue in a secondary analysis of data from an outpatient clinical trial of buprenorphine treatment for concurrent cocaine and opioid dependence (13 weeks, N=200). The association between cigarette smoking (lifetime cigarette smoking status, number of cigarettes smoked per day prior to study entry) and short-term treatment outcome (% of urine samples positive for cocaine or opioids, treatment retention) was evaluated with analysis of covariance, bivariate correlations, and multivariate linear regression. Nicotine-dependent smokers (66% of participants) had a significantly higher percentage of cocaine-positive urine samples than non-smokers (12% of participants) (76% vs. 62%), but did not differ in percentage of opioid-positive urine samples or treatment retention. Number of cigarettes smoked per day at baseline was positively associated with percentage of cocaine-positive urine samples, even after controlling for baseline sociodemographic and drug use characteristics, but was not significantly associated with percentage of opioid-positive urine samples or treatment retention. These results suggest that cigarette smoking is associated with poorer short-term outcome of outpatient treatment for cocaine dependence, but perhaps not of concurrent opioid dependence, and support the importance of offering smoking cessation treatment to cocaine-dependent patients.

Topics: Adult; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Cocaine-Related Disorders; Female; Humans; Male; Middle Aged; Smoking; Substance-Related Disorders; Time Factors; Tobacco Use Disorder; Treatment Outcome

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination ('speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday-Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday-Friday mornings (0900-1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); 'speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.

Topics: Adolescent; Adult; Buprenorphine; Choice Behavior; Cocaine; Cocaine-Related Disorders; Delayed-Action Preparations; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Seeking Behavior; Female; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Reinforcement Schedule; Reward; Substance Withdrawal Syndrome

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies.

Topics: Adolescent; Adult; Buprenorphine; Cocaine-Related Disorders; Directive Counseling; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Patient Compliance; Reward; Secondary Prevention

This study compared the relative efficacy of low-magnitude, contingent monetary vouchers, contingent buprenorphine medication, and standard counseling in promoting abstinence from illicit opioids and cocaine among opioid-dependent adults. Following an 8-week baseline period during which participants received buprenorphine maintenance treatment with no contingencies in place, 60 participants were randomly assigned to one of 3 treatment groups for 12 weeks: (a) Participants in the voucher group earned vouchers for each opioid- and cocaine-negative urine sample, in accordance with an escalating schedule. Continuous abstinence resulted in voucher earnings equivalent to a total of 269 US dollars, which participants could exchange for material reinforcers of their choice. (b) Participants in the medication contingency group received half their scheduled buprenorphine dose for clinic attendance and the other half for remaining abstinent from opiates and cocaine. Thus, they received only half of their scheduled dose on submission of an opioid- and/or cocaine-positive urine sample. (c) Participants in standard treatment did not receive programmed consequences contingent on urinalysis results. All participants were maintained with buprenorphine according to a 3-times-per-week dosing regimen and participated in behavioral drug counseling. Retention rate did not significantly differ across the groups; however, participants in the medication contingency group achieved significantly more weeks of continuous abstinence from opiates and cocaine compared with participants in the voucher group (Ms = 5.95 and 2.90, respectively). Results suggest that the use of medication-based contingencies in combination with behavioral therapy in promoting drug abstinence may have clinical utility. Limitations of the study are discussed.

Topics: Adult; Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Female; Health Care Costs; Humans; Male; Middle Aged; Opioid-Related Disorders; Reinforcement Schedule

The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care, office-based buprenorphine-naloxone treatment of opioid dependence.. We conducted a 24-week randomized, controlled clinical trial with 166 patients assigned to one of three treatments: standard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing. Standard medical management was brief, manual-guided, medically focused counseling; enhanced management was similar, but each session was extended. The primary outcomes were the self-reported frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids.. The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens (standard medical management and once-weekly medication dispensing, 44 percent; standard medical management and thrice-weekly medication dispensing, 40 percent; and enhanced medical management and thrice-weekly medication dispensing, 40 percent; P=0.82) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids. All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use, but there were no significant differences among the treatments. The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving standard medical management and once-weekly medication dispensing (48 percent) or thrice-weekly medication dispensing (43 percent) or enhanced medical management and thrice-weekly medication dispensing (39 percent) (P=0.64). Adherence to buprenorphine-naloxone treatment varied; increased adherence was associated with improved treatment outcomes.. Among patients receiving buprenorphine-naloxone in primary care for opioid dependence, the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing. Strategies to improve buprenorphine-naloxone adherence are needed. (ClinicalTrials.gov number, NCT00023283 [ClinicalTrials.gov].).

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Counseling; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence.. Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance.. Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study.. Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.

Topics: Adult; Analgesics, Opioid; Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Comorbidity; Female; Humans; Male; Methadone; Opioid-Related Disorders; Substance Abuse Detection; Token Economy; Treatment Outcome

We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p=0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p=0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Psychotherapy; Treatment Outcome

Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence.. Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling.. The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events.. A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cocaine-Related Disorders; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Treatment Outcome

Sublingual buprenorphine, a long-acting, partial mu-opioid agonist, is as effective as methadone in the treatment of heroin dependence, with a better safety profile due to its antagonist activity. However, the safety of therapeutic doses (8 to 16 mg) that might be diverted for intravenous (i.v.) use has not been demonstrated. To evaluate the safety and possible ceiling effects of buprenorphine administered i.v. to experienced opioid users, buprenorphine was administered to 6 nondependent opioid abusers residing on a research unit; the doses tested, in separate sessions, were 12 mg buprenorphine sublingual, i.v./sublingual placebo, and escalating i.v. buprenorphine (2, 4, 8, 12, and 16 mg). Physiologic and subjective measures were collected for 72 hours post-drug administration. Buprenorphine minimally but significantly increased systolic blood pressure. Changes in heart rate or oxygen saturation among the 7 drug conditions were not statistically significant. The mean maximum decrease in oxygen saturation from baseline was greatest for the 8-mg i.v. dose. Buprenorphine produced positive mood effects, although with substantial variability among participants. Onset and peak effects occurred earlier following i.v. administration: peak i.v. effects occurred between 0.25 and 3 hours; peak sublingual effects occurred at 3 to 7 hours. Duration of effects varied among the outcome measures. The dose-response curves were flat for most parameters, particularly subjective measures. Side effects were mild except in one participant who experienced severe nausea and vomiting after the 12-mg i.v. dose. Buprenorphine appears to have a ceiling for cardiorespiratory and subjective effects and a high safety margin even when taken by the i.v. route.

Topics: Administration, Sublingual; Adult; Arousal; Attention; Blood Pressure; Buprenorphine; Cocaine-Related Disorders; Dose-Response Relationship, Drug; Female; Heart Rate; Heroin Dependence; Humans; Infusions, Intravenous; Male; Narcotic Antagonists; Narcotics; Pain Measurement; Reflex, Pupillary; Substance Abuse, Intravenous

During 3 months where contingency management (CM) had an escalating value for each consecutive drug-free urine (escalating CM), cocaine- and heroin-abusing patients significantly increased drug-free urines. The 'escalating CM' was eliminated during months 4-6 to assess any reduction in drug-free urines.. Patients who completed a 3-month, randomized, double-blind, trial evaluating CM versus non-CM and desipramine (DMI) versus placebo, had an 'escalating CM' eliminated during months 4-6. The CM and non-CM groups were compared using thrice-weekly urine samples.. Out-patient buprenorphine maintenance for 6 months.. All 75 of the 160 original study patients who completed month 3 of the clinical trial.. The 'escalating CM' was eliminated for all 3 months and during months 5 and 6 the response requirement was also increased to two and then three consecutive drug-free urines in order to obtain a voucher.. Urine toxicology for opiates and cocaine.. After eliminating the 'escalating CM', the CM group showed a decline in combined opioid- and cocaine-free urines. This decline within the CM group was greater in those treated with DMI than placebo.. Buprenorphine with DMI maintained drug abstinence after eliminating the 'escalating CM', but not after increasing the response requirement, suggesting the need for more intensive psychosocial interventions during CM.

Topics: Adult; Antidepressive Agents, Tricyclic; Behavior Control; Buprenorphine; Cocaine-Related Disorders; Desipramine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Narcotics; Opioid-Related Disorders; Token Economy; Treatment Outcome

Co-dependence on opiates and cocaine occurs in about 60% of patients entering methadone treatment and has a poor prognosis. However, we recently found that desipramine (DMI) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients. Furthermore, contingency management (CM) has been quite potent in reducing cocaine abuse during methadone maintenance. To test the efficacy of combining CM with these medications we designed a 12-week, randomized, double blind, four cell trial evaluating DMI (150 mg/day) or placebo plus CM or a non-contingent voucher control in 160 cocaine abusers maintained on buprenorphine (median 16 mg daily). Cocaine-free and combined opiate and cocaine-free urines increased more rapidly over time in those treated with either DMI or CM, and those receiving both interventions had more drug-free urines (50%) than the other three treatment groups (25-29%). Self reported opiate and cocaine use and depressive and opioid withdrawal symptoms showed no differences among the groups and symptom levels did not correlate with urine toxicology results. Lower DMI plasma levels (average 125 ng/ml) were associated with greater cocaine-free urines. DMI and CM had independent and additive effects in facilitating cocaine-free urines in buprenorphine maintained patients. The antidepressant appeared to enhance responsiveness to CM reinforcement.

Topics: Adult; Aged; Ambulatory Care; Analysis of Variance; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Connecticut; Desipramine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Treatment Outcome

Depression is common among patients who abuse both opiates and cocaine, and its treatment has had mixed success. This study compares buprenorphine-maintained patients with lifetime major depressive disorder (MDD, N = 53) with those never depressed (ND, N = 96) on cocaine and opiate-free urines during a 12-week outpatient double-blind, placebo-controlled, randomized clinical trial. The 149 subjects were assigned to four groups: 1) desipramine (DMI) + contingency management (CM); 2) DMI + noncontingency management (NCM); 3) placebo + CM; and 4) placebo + NCM. Depression assessments included Hamilton Depression Rating Scale, Center for Epidemiological Studies Depression Inventory, and Structured Clinical Interview for DSM-IV interview for diagnosis of lifetime MDD. Urine toxicologies were performed thrice weekly and the CES-D was performed monthly. The MDD group had a larger proportion of females (45% vs 21%, P = 0.02) and were more likely to be married (13.2% vs 7.3%, P = 0.02) than the ND group. Treatment retention did not vary by depression status. Hierarchical Linear Modeling found that depressive symptoms decreased comparably across the four treatment groups. Although participation in CM improved drug-free urines more for patients with MDD than for the ND group (Z = 2.44, P = 0.01), treatment with DMI was significantly more efficacious for the ND group than for the MDD group (Z = -2.89, P = 0.003). These results suggest that patients with MDD may respond better to behavioral treatments such as CM than to desipramine plus buprenorphine. The ND cocaine-abusing, opiate-dependent patients may be more responsive to the anticraving effects of DMI.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Depressive Disorder, Major; Desipramine; Diagnosis, Dual (Psychiatry); Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prognosis; Psychiatric Status Rating Scales; Treatment Outcome

This study examined the usefulness of baseline cocaine urine toxicology results and self-reported days of cocaine use in predicting treatment response in cocaine- and opioid-dependent subjects. Ninety-nine male and 52 female subjects, maintained on buprenorphine, participated in a 24-week, randomized, double-blind, four-cell trial that evaluated desipramine (150 mg/d) or placebo plus contingency management or a noncontingent voucher control. Out of 151, 102 (67%) subjects had cocaine-positive and 49 (32%) cocaine-negative urines at the beginning of treatment. For the previous 30 days before study participation, 91 (60%) subjects reported using cocaine 15 or less days (low baseline cocaine use) and 60 (40%) subjects reported more than 15 days (high baseline cocaine use). By using the treatment effectiveness score (TES) as the outcome measure, a negative urine for cocaine at baseline predicted a better outcome during a 24-week trial for cocaine and opioid use. There also was a significant interaction between baseline cocaine urine results and desipramine response with the urine cocaine-negative group showing greater desipramine response than placebo for opioid and cocaine use. Self-reported cocaine use at baseline did not show significant predictive power for TES scores during the clinical trial. These results suggest that baseline cocaine urine results should be considered as stratifying variables in clinical trials for cocaine dependence.

Topics: Adult; Analysis of Variance; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Desipramine; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Self Disclosure; Time Factors; Token Economy; Treatment Outcome

The purpose of this open-label, uncontrolled study was to evaluate the feasibility of administering off-label buprenorphine in combination with ancillary medications for inpatient short-term detoxification of heroin-dependent patients at a psychiatric facility. A sample of 20 heroin-dependent patients admitted to an urban psychiatric hospital was administered buprenorphine 6, 4, and 2 mg/day during the first, second, and third day of detoxification, respectively, and then observed during the fourth and fifth day. Eighty-five percent of the subjects abused other substances, 75% reported cocaine abuse/dependence, 75% had comorbid mood disorders. All subjects completed the medication phase of the study. No clinically significant adverse events were reported. There was a significant decrease in the Clinical Investigation Narcotic Assessment (CINA) total score between baseline and days 2 through 5. The results suggest that buprenorphine is well tolerated and may be beneficial for medically supervised short-term withdrawal from heroin for hospitalized psychiatric patients.

Topics: Adult; Analgesics, Opioid; Baltimore; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Emergency Services, Psychiatric; Female; Heroin Dependence; Humans; Male; Middle Aged; Mood Disorders; Narcotic Antagonists; Patient Satisfaction; Pilot Projects; Substance Withdrawal Syndrome

The utility of the crossover design in substance abuse research was examined in a 26-week, double-blind clinical trial that evaluated the efficacy of desipramine (0 or 150 mg/day) in 109 male and female cocaine- and opiate-dependent patients maintained on buprenorphine (12 mg/day) or methadone (65 mg/day). After being stabilized on buprenorphine or methadone (weeks 1-2), half of the patients were randomly assigned to receive desipramine for the first half of the trial and placebo for the second, with the order reversed for the second half. Analyses using hierarchical linear models (HLM) indicated that desipramine reduced the use of opiates only when administered at the start (rather than the middle) of the trial, whereas cocaine use was reduced when desipramine was introduced at either time.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Tricyclic; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Cross-Over Studies; Desipramine; Double-Blind Method; Female; Humans; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Placebos; Time Factors; Treatment Outcome

The effect of sublingual buprenorphine on cigarette smoking was examined in 23 adult men with DSM III-R diagnosis of concurrent opiate and cocaine dependence. After admission to a clinical research ward, subjects were detoxified with methadone (10-50 mg/day), then were drug-free for 6 days before random assignment to either 4 or 8 mg/day of buprenorphine. Gradually increasing daily sublingual doses of buprenorphine were administered for 5 days, then subjects were maintained on 4 or 8 mg/day of buprenorphine for 12 days. Each subject's preferred brand of cigarettes was available ad libitum throughout the study. Five responses (FR 5) on a key were required to earn each cigarette. The time and number of cigarettes were recorded by an automated cigarette dispenser. Subjects acquired significantly more cigarettes during the buprenorphine induction and maintenance phases (25.5+/-2.0) than during the drug-free phase (18.5+/-1.8; p<0.0002). During buprenorphine induction, the number of cigarettes acquired was positively correlated with increasing doses of buprenorphine (p<0.001) and the inter-cigarette interval was significantly shorter during buprenorphine maintenance than during drug-free conditions (p<0.001). These data showed that daily administration of the partial mu opioid agonist buprenorphine was associated with increased smoking in men concurrently dependent on opiates and cocaine. These findings are consistent with previous reports of opioid-cigarette interactions.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cocaine-Related Disorders; Humans; Inpatients; Male; Narcotic Antagonists; Opioid-Related Disorders; Smoking; Treatment Outcome

This study targeted poly-drug (cocaine plus heroin) abstinence among buprenorphine-maintained participants with a 12-week voucher-based reinforcement therapy (VBRT) phase versus a yoked control condition. Baseline levels of cocaine and heroin use were significant predictors of treatment outcome, regardless of treatment assignment. Overall, there were no significant group differences on treatment outcome. However, among the subsample that produced one or more poly-drug-free urine results, VBRT participants had significantly increased cocaine-but not heroin and poly-drug-abstinence, although all results were in the predicted direction. Results suggest that for those who achieve poly-drug abstinence, VBRT may enhance treatment outcome. However, improved interventions, perhaps targeting single-drug abstinence, increasing reinforcement magnitude, or both, may be necessary to promote initial poly-drug abstinence in this population.

Topics: Adolescent; Adult; Breath Tests; Buprenorphine; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Psychiatric Status Rating Scales; Substance Abuse Detection; Substance-Related Disorders; Time Factors; Treatment Outcome

Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose.. After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use.. There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%).. At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Psychiatric Status Rating Scales

We examined the effects of disulfiram versus placebo on cocaine dependence in buprenorphine-maintained subjects.. Opioid and cocaine dependent subjects (n = 20) were induced onto buprenorphine maintenance, then randomized to disulfiram (250 mg q.d. ; n = 11) or placebo (n = 9) treatment for 12 weeks.. Groups were comparable at baseline on demographic measures and on baseline measures of drug-use severity. Fifteen subjects completed the study, including 8 subjects randomized to disulfiram (72.7%) and 7 subjects randomized to placebo (77.8%). The total number of weeks abstinent from cocaine was significantly greater on disulfiram versus placebo (mean +/- SD: 7.8 +/- 2.6 vs. 3.3 +/- 0.5, p <.05) and the number of days to achieving 3 weeks (24.6 +/- 15.1 vs. 57.8 +/- 7.7, p <.01) of continuous cocaine abstinence was significantly lower in disulfiram compared with placebo. The number of cocaine-negative urine tests during the trial were also higher on disulfiram (14.7) than on placebo (8.6); furthermore, subjects in the disulfiram group achieved consistently higher rates of cocaine-negative urine tests in each 3-week interval and the increase over time was faster in the disulfiram compared with placebo.. This preliminary study suggests the potential efficacy of disulfiram versus placebo for treatment of cocaine dependence in buprenorphine-maintained patients.

Topics: Adult; Alcohol Deterrents; Buprenorphine; Chi-Square Distribution; Cocaine-Related Disorders; Disulfiram; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Substance Abuse Detection; Time Factors

Opioid dependence is a chronic, relapsing disorder with important public health implications.. In a 17-week randomized study of 220 patients, we compared levomethadyl acetate (75 to 115 mg), buprenorphine (16 to 32 mg), and high-dose (60 to 100 mg) and low-dose (20 mg) methadone as treatments for opioid dependence. Levomethadyl acetate and buprenorphine were administered three times a week. Methadone was administered daily. Doses were individualized except in the group assigned to low-dose methadone. Patients with poor responses to treatment were switched to methadone.. There were 55 patients in each group; 51 percent completed the trial. The mean (+/-SE) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate (89+/-6), buprenorphine (96+/-4), and high-dose methadone (105+/-4) than for those receiving low-dose methadone (70+/-4, P<0.001). Continued participation was also significantly more frequent among patients receiving high-dose methadone than among those receiving levomethadyl acetate (P=0.02). The percentage of patients with 12 or more consecutive opioid-negative urine specimens was 36 percent in the levomethadyl acetate group, 26 percent in the buprenorphine group, 28 percent in the high-dose methadone group, and 8 percent in the low-dose methadone group (P=0.005). At the time of their last report, patients reported on a scale of 0 to 100 that their drug problem had a mean severity of 35 with levomethadyl acetate, 34 with buprenorphine, 38 with high-dose methadone, and 53 with low-dose methadone (P=0.002).. As compared with low-dose methadone, levomethadyl acetate, buprenorphine, and high-dose methadone substantially reduce the use of illicit opioids.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Methadone; Methadyl Acetate; Middle Aged; Narcotics; Opioid-Related Disorders; Treatment Outcome

Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence.. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10.. In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence.. Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Desipramine; Drug Administration Schedule; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Sex Factors; Treatment Outcome

This study a) compared the effects of buprenorphine versus methadone maintenance on benzodiazepine and alcohol use and b) evaluated the prognostic significance of gender and psychopathology and their interaction with maintenance treatment. Eighty male and 36 female patients were randomly assigned to daily sublingual buprenorphine (4 or 12 mg) or oral methadone (20 or 65 mg). Maintenance medication was not associated with significant differences in alcohol or benzodiazepine use. Rates of abstinence from illicit opioids were significantly higher for females, within the buprenorphine 4-mg group, females also had significantly better retention, lower rates of opioid-positive urine samples, and higher rates of abstinence from illicit opioids. Lifetime sedative dependence was associated with significantly better retention, decreased rates of cocaine-positive urine samples, and increased rates of cocaine abstinence; among buprenorphine- but not methadone-maintained patients, it was also associated with increased rates of abstinence from illicit opioids.

Topics: Adult; Alcoholism; Antisocial Personality Disorder; Benzodiazepines; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Depressive Disorder; Double-Blind Method; Female; Humans; Male; Methadone; Opioid-Related Disorders; Patient Dropouts; Prognosis; Sex Factors; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

We use a novel, longitudinal approach to describe average time spent in opioid use disorder (OUD) cascade of care stages for people with HIV (PWH) and with OUD, incorporating four definitions of treatment retention. Using this approach, we describe the impact of cocaine or hazardous alcohol use on time spent retained on buprenorphine.. We followed PWH with OUD enrolled in the Johns Hopkins HIV Clinical Cohort from their first buprenorphine treatment episode between 2013 and 2020. We estimated 4-year restricted mean time spent on buprenorphine below buprenorphine retention threshold, on buprenorphine above retention threshold, off buprenorphine and in HIV care, loss to follow-up, and death. Retention definitions were based on retention threshold (180 vs 90 days) and allowable treatment gap (7 vs 30 days). Differences in 2-year restricted mean time spent retained on buprenorphine were estimated for patients with and without cocaine or hazardous alcohol use.. The study sample (N = 179) was 63% male, 82% non-Hispanic Black, and mean age was 53 (SD 8) years. Patients spent on average 13.9 months (95% CI 11.4, 16.4) on buprenorphine over 4 years. There were differences in time spent retained on buprenorphine based on the retention definition, ranging from 6.5 months (95% CI 4.6, 8.5) to 9.6 months (95% CI 7.4, 11.8). Patients with cocaine use spent fewer months retained on buprenorphine. There were no differences for patients with hazardous alcohol use.. PWH with OUD spend relatively little time receiving buprenorphine in their HIV primary care clinic. Concurrent cocaine use at buprenorphine initiation negatively impact time on buprenorphine.

Topics: Buprenorphine; Cocaine; Cocaine-Related Disorders; Female; HIV Infections; Humans; Male; Middle Aged; Opioid-Related Disorders

Substance use disorder (SUD) and infectious disease (ID) care integration may lead to improvements in SUD and ID outcomes. We assessed implementation of integrating peer-supported SUD care in an outpatient ID setting.. In this implementation study, we describe REcovery in Specialty care Through medication and OutREach (RESTORE), a low-threshold SUD program implemented in a Baltimore outpatient ID clinic. Key program components were clinician training and support in SUD care, prescription of SUD treatment medications, and peer-based psychosocial support provided by peer recovery specialists. We assessed clinician adoption of RESTORE and compared patient outcomes from baseline to 6 months.. Between January 2019 and January 2022, the number of ID clinicians (N=61) who prescribed buprenorphine increased eightfold from 3 (5%) to 24 (39%). Of 258 ID patients referred to RESTORE, 182 (71%) engaged, 137 consented to study participation. Mean age in the study sample was 52.1 (SD=10.4), 63% were male, 84% were Black/African-American. Among 127 (93%) who completed 6-month follow-up, fewer participants reported illicit/non-prescribed opioid use in the past 30 days at follow-up (32%) compared to baseline (52%; p<0.001). Similar reductions were noted for cocaine use (47% to 34%; p=0.006), emergency department visits (23% to 9%; p=0.002), and inpatient hospitalizations (15% to 7%; p=0.025).. SUD care integration into an outpatient ID care setting using a peer-supported implementation strategy was adopted by clinicians and improved clinical outcomes for patients. This strategy is a promising approach to treating people with infectious diseases and SUD.

Topics: Buprenorphine; Cocaine-Related Disorders; Female; Hospitalization; Humans; Male; Opioid-Related Disorders; Outpatients; Substance-Related Disorders

Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized.. We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants being treated with methadone or buprenorphine (in a buprenorphine-naloxone formulation) for up to 16 weeks. A smartphone app was used to assess stress and craving at three random times per day over the course of the study.. Five basic patterns of use were identified: frequent opioid use, frequent cocaine use, frequent dual use (opioids and cocaine), sporadic use, and infrequent use. These patterns were differentially associated with medication (methadone vs. buprenorphine), race, age, drug-use history, drug-related problems prior to the study, stress-coping strategies, specific triggers of use events, and levels of cue exposure, craving, and negative mood. Craving tended to increase before use in all except those who used sporadically. Craving was sharply higher during the 90 min following moderate-to-severe stress in those with frequent use, but only moderately higher in those with infrequent or sporadic use.. People who share similar patterns of drug-use during treatment also tend to share similarities with respect to psychological processes that surround instances of use, such as stress-induced craving. Cluster analysis combined with smartphone-based experience sampling provides an effective strategy for studying how drug use is related to personal and environmental factors.

Topics: Affect; Buprenorphine; Cocaine-Related Disorders; Craving; Ecological Momentary Assessment; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Smartphone; Stress, Psychological

Despite rising morbidity and mortality from the opioid epidemic and other addictions, people who inject drugs (PWID) remain understudied regarding pain outcomes. Data among PWID regarding chronic pain and drug use, including non-medical use of opioids, is largely unknown. We examined the prevalence of chronic pain and drug use for pain in this population.. Standardized surveys captured self-report of demographics, chronic pain, and non-prescription drug use in 203 PWID in an urban syringe services program between April and November 2016. Chronic pain was defined as self-report of chronic pain diagnosis or persistent pains over the past 6 months.. Overall, 47% (95% CI, 40%-54%) of PWID reported chronic pain, while 35% (95% CI, 29%-42%) reported non-prescription drug use of any type for pain. Among those with chronic pain, drug use to treat pain was commonly reported (76%; 95% CI, 66%-83%). Non-medical opioid use did not differ among PWID with or without chronic pain or drug use for pain. A multivariable logistic regression model showed chronic pain was more likely among non-Hispanic whites and those with arthritis, older age, and homelessness.. Chronic pain serves as an important factor in the persistence of drug use in more than one-third of PWID in this sample. The high prevalence of chronic pain with drug use for pain suggests that proper pain management is likely to be an essential component of preventing or regressing injection drug use in PWID, with data needed on effective interventions for this population.

Topics: Adolescent; Adult; Age Factors; Analgesics, Opioid; Arthritis; Baltimore; Black or African American; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Ill-Housed Persons; Male; Middle Aged; Needle-Exchange Programs; Odds Ratio; Opioid-Related Disorders; Prevalence; Risk Factors; Substance Abuse, Intravenous; White People; Young Adult

Developing new medications for the treatment of cocaine dependence continues to be a research priority. Compelling evidence indicates that mixed opioid receptor agonists, particularly bifunctional compounds that target nociceptin/orphanin FQ peptide (NOP) and mu opioid receptors, may be useful for the treatment of cocaine addiction. Here, we verify that potent and selective pharmacological activation of NOP receptors is sufficient to reduce relevant facets of cocaine addiction in animal models. Accordingly, we determined whether systemic injections of the small molecule AT-312 (0, 1, 3 mg/kg) could reduce operant cocaine self-administration, motivation for cocaine, and vulnerability to cocaine relapse in rats. Results indicate that a potent and selective NOP receptor agonist was equally efficacious in reducing the number of cocaine infusions in short (1-hour), as well as long (6-hour) access sessions. When tested on an economic-demand reinforcement schedule, AT-312 reduced Q

Topics: Animals; Buprenorphine; Cocaine; Cocaine-Related Disorders; Cycloheptanes; Indoles; Male; Nociceptin Receptor; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Reinforcement Schedule; Self Administration

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Philadelphia; Primary Health Care; Retrospective Studies; Treatment Outcome; Vulnerable Populations

Topics: Acetaminophen; Adult; Buprenorphine; Cocaine-Related Disorders; Diagnosis, Differential; Diarrhea; Drug Combinations; Female; Humans; Illicit Drugs; Naloxone; Narcotic Antagonists; Nausea; Opioid-Related Disorders; Oxycodone; Substance Abuse Detection; Vomiting

To analyse predictors of heroin abstinence in opiate substitution therapy (OST) based on frequency of crack use and its interactions with other predictors in a clinical non-experimental setting.. Retrospective study.. A community drug service in London, UK.. 325 clients starting OST between 2010 and 2014 (197 methadone and 128 buprenorphine).. Logistic regression models (a general model and separate models for methadone and buprenorphine) assessed demographic and clinical data as predictors of heroin abstinence at one year after treatment start (or at the date of transfer to another service).. For the general model participants choosing methadone were more likely to use heroin at follow up (OR=2.36, 95% CI: 1.40-3.17) as were daily crack users on methadone (OR=2.62, 95% CI: 0.96-7.16). For the methadone model only daily crack use predicted heroin use at follow up (OR=2.62, 95% CI: 0.96-7.16). For buprenorphine, higher amounts of baseline heroin use, lower buprenorphine dose and daily drinking predicted heroin use at follow up (OR=0.85, 95% CI: 0.75-0.95; OR=1.31, 95% CI: 1.06-1.60 and OR=6.04, 95% CI: 1.26-28.92). Both use of cannabis and depression increased likelihood of heroin abstinence for clients not using crack compared to occasional (OR=6.68, 95% CI: 0.37-119.59; OR=106.31, 95% CI: 3.41-3313.30) and daily (OR=57.49 (95% CI: 2.37-1396.46; OR=170.99 (95% CI: 4.61-6339.47) users.. Most of the predictors in the general model were found significant only in the buprenorphine but not in the methadone model, suggesting that a general model has little predictive value. Crack use was a significant predictor of heroin abstinence at follow up in all models, however for buprenorphine only when depression or cannabis use was present. Further research is needed to assess effective treatment approaches for the growing population of dual users.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Female; Heroin Dependence; Humans; London; Male; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Retrospective Studies; Treatment Outcome; Young Adult

Urine adulteration is a concern among patients treated for opioid use disorder. Quantitative urine testing for buprenorphine (B) and norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can facilitate constructive conversations with patients that may lead to modifications in the treatment plan, and strengthening of the patient-provider relationship.. Three cases are presented in which discordant urine B and NB levels were recognized. Each patient was submerging buprenorphine/naloxone strips in their urine to mask ongoing illicit drug use. The authors used an approach to addressing intentional adulteration of urine samples that adheres to the principles of harm-reduction, the centrality of the patient-provider relationship, and the acknowledgment that ongoing illicit drug use and subsequent dishonesty about disclosure may be common among persons with substance use disorders. Each of the three patients ultimately endorsed diluting their urine, which allowed for strengthening of the patient-provider relationship and modifications to their treatment plans. Two of the three patients stabilized and achieved abstinence, while the third was eventually referred to a methadone treatment program.. Providers should routinely monitor B and NB levels, rather than qualitative screening alone, and discordant levels should elicit a timely conversation with the patient. The authors use of a nonjudgmental approach to address urine adulteration, including giving patients an opportunity to reflect on potential solutions, has been effective at helping patients and providers to reestablish a therapeutic alliance and maintain retention in treatment.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Drug Contamination; Female; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Substance Abuse Detection

Opioid dependence is a major health concern across the world and does also occur in adolescents. While opioid substitution treatment (OST) has been thoroughly evaluated in adult populations, very few studies have examined its use in adolescents. There are concerns that OST is underutilised in adolescents with heroin dependence. We sought to measure changes in drug use among adolescents receiving OST and also to examine treatment attrition during the first 12 months of this treatment.. We included all heroin dependent patients aged under 18.5 years commencing OST at one outpatient multidisciplinary adolescent addiction treatment service in Dublin, Ireland. Psycho-social needs were also addressed during treatment. Drug use was monitored by twice weekly urine drugs screens (UDS). Change in the proportion of UDS negative for heroin was examined using the Wilcoxon signed rank test. Attrition was explored via a Cox Regression multivariate analysis.. OST was commenced by 120 patients (51% female and mean age 17.3 years). Among the 39 patients who persisted with OST until month 12, heroin abstinence was 21% (95% confidence interval [CI] = 9-36%) at month three and it was 46% (95% CI = 30-63%) at month 12. Heroin use declined significantly from baseline to month three (p < 0.001) and from month three to month 12 (p = 0.01). Use of other drugs did not change significantly. People using cocaine during month 12 were more likely to be also using heroin (p = 0.02). Unplanned exit occurred in 25% patients by 120 days. The independent predictors of attrition were having children, single parent family of origin, not being in an intimate relationship with another heroin user and evidence of cocaine use just before treatment entry.. We found that heroin dependent adolescent patients achieved significant reductions in heroin use within three months of starting OST and this improved further after a year of treatment, about half being heroin abstinent at that stage. Patient drop out from treatment remains a challenge, as it is in adults. Cocaine use before and during treatment may be a negative prognostic factor.

Topics: Adolescent; Buprenorphine; Cocaine-Related Disorders; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Medication Adherence; Methadone; Opiate Substitution Treatment; Patient Dropouts

Urine drug tests (UDTs) are recommended to monitor patients treated for opioid use disorder in primary care. The aims are to (1) estimate the frequency of self-report and UDT results of opioid and cocaine use and (2) evaluate the association between treatment time with non-disclosure of opioid or cocaine use and having a positive UDT.. We conducted a retrospective review of patients enrolled in a primary care-based buprenorphine program between January 2011-April 2013. We describe three clinical visits types: no disclosure of opioid/cocaine use and positive UDT; disclosure of opioid or cocaine use and a negative or positive UDT; and no disclosure of opioid or cocaine use and a negative UDT. We fit generalized estimating equations logistic regression models to evaluate whether treatment time is associated with non-disclosure of opioids or cocaine use and a positive UDT.. Among all UDT results (n = 1755) from 130 patients, 10% were positive for illicit opioids and 4% for cocaine. Among UDTs with illicit opioid or cocaine positive results, in 57% and 76% of these scenarios, the patient did not disclose. The odds of non-disclosure and having a positive UDT was higher in the first 180 days for opioids and 90 days for cocaine.. Among primary care patients treated with buprenorphine, a small but substantial percentage of UDTs were cocaine or opioid positive. As treatment time increased, non-disclosure was less common but persisted even after six months. Among primary care patients treated with buprenorphine, UDTs contribute information to optimize clinical care.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; Retrospective Studies; Self Report; Substance Abuse Detection; Young Adult

To test if polysubstance use profiles and drug-related outcomes differ between those receiving and not receiving opioid substitution therapies (OST) among people who inject drugs (PWID).. An annual cross-sectional, sentinel sample of PWID across Australia.. Data came from 3 years (2011-13) of the Illicit Drug Reporting System (IDRS).. A total of 2673 participants who injected drugs from the combined national IDRS samples of 2011 (n = 868), 2012 (n = 922) and 2013 (n = 883).. Latent class analysis (LCA) was used to summarize participants' self-reported use of 18 types of substances, with the resulting polysubstance use profiles then associated with participant experience of a number of drug-related outcomes.. Polysubstance use profiles exhibiting a broad range of substance use were generally at increased risk of negative drug-related outcomes, whether or not participants were receiving OST, including thrombosis among OST receivers [odds ratio (OR) = 2.13, 95% confidence intervals (CI) = 1.09-4.17], injecting with used needles among OST receivers and non-receivers, respectively (OR = 2.78, 95% CI = 1.50-5.13; OR = 2.15, 95% CI = 1.34-3.45) and violent criminal offences among OST receivers and non-receivers, respectively (OR =2.30, 95% CI = 1.16-4.58; OR = 1.87, 95% CI = 1.14-3.07). An important exception was non-fatal overdose which was related specifically to a class of PWID who were not receiving OST and used morphine frequently (OR = 1.83, 95% CI = 1.06-3.17) CONCLUSION: Regardless of opioid substitution therapies usage, people who inject drugs who use a broad-range of substances experience greater levels of injecting-related injuries and poorer health outcomes and are more likely to engage in criminal activity than other groups of people who inject drugs.

Topics: Abscess; Adolescent; Adult; Alcoholism; Amphetamine-Related Disorders; Analgesics, Opioid; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cross-Sectional Studies; Drug Overdose; Female; Heroin Dependence; Humans; Male; Marijuana Abuse; Methadone; Middle Aged; Needle Sharing; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance-Related Disorders; Thrombosis; Violence; Young Adult

Cocaine decreases methadone and buprenorphine plasma concentrations. HIV infection and/or antiretroviral medication use may impact these relationships. We sought to determine the association between recent cocaine use and methadone and buprenorphine concentrations in HIV-infected and uninfected subjects in clinical care. R- and S-methadone or buprenorphine and norbuprenorphine concentrations were assessed at 0.5, 1, 2, and 24 hours after dosing in subjects with confirmed cocaine use and abstinence. We compared methadone and buprenorphine concentrations for cocaine use vs. abstinence, by HIV status in 16 subjects receiving methadone (6 HIV-infected) and 17 receiving buprenorphine (8 HIV-infected). With recent cocaine use, peak R-methadone (244 vs. 297 ng/mL, p = 0.03) and peak S-methadone (285 vs. 339 ng/mL); p = 0.03 concentrations were lower in HIV-uninfected subjects only. Peak buprenorphine and norbuprenorphine concentrations were unchanged regardless of cocaine use or HIV status. Cocaine may decrease methadone concentrations in HIV-uninfected subjects. HIV infection or its treatment may attenuate cocaine's effect on methadone.

Topics: Adult; Anti-HIV Agents; Buprenorphine; Cocaine; Cocaine-Related Disorders; Drug Interactions; Female; HIV Infections; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Stereoisomerism; Time Factors

Topics: Abortion, Legal; Buprenorphine; Civil Rights; Cocaine-Related Disorders; Female; Fetal Death; Halfway Houses; Humans; Legal Guardians; Medication Adherence; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Substance Abuse Detection; United States

Topics: Animals; Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clinical Trials as Topic; Cocaine-Related Disorders; Counseling; Dopamine; Drug Discovery; Drug Industry; Humans; Ibogaine; Lobeline; Molecular Targeted Therapy; Naloxone; Naltrexone; Oligopeptides; Opioid-Related Disorders; Pleasure; Rats; Receptors, Nicotinic; Reward; Substance-Related Disorders; Tobacco Use Disorder; Vaccines; Vesicular Monoamine Transport Proteins

On October 2012, Hurricane Sandy struck New York City, resulting in unprecedented damages, including the temporary closure of Bellevue Hospital Center and its primary care office-based buprenorphine program.. At 6 months, we assessed factors associated with higher rates of substance use in buprenorphine program participants that completed a baseline survey one month post-Sandy (i.e. shorter length of time in treatment, exposure to storm losses, a pre-storm history of positive opiate urine drug screens, and post-disaster psychiatric symptoms).. Risk factors of interest extracted from the electronic medical records included pre-disaster diagnosis of Axis I and/or II disorders and length of treatment up to the disaster. Factors collected from the baseline survey conducted approximately one month post-Sandy included self-reported buprenorphine supply disruption, health insurance status, disaster exposure, and post-Sandy screenings for PTSD and depression. Outcome variables reviewed 6 months post-Sandy included missed appointments, urine drug results for opioids, cocaine, and benzodiazepines.. 129 (98%) patients remained in treatment at 6 months, and had no sustained increases in opioid-, cocaine-, and benzodiazepine-positive urine drug tests in any sub-groups with elevated substance use in the baseline survey. Contrary to our initial hypothesis, diagnosis of Axis I and/or II disorders pre-Sandy were associated with significantly less opioid-positive urine drug findings in the 6 months following Sandy compared to the rest of the clinic population.. These findings demonstrate the adaptability of a safety net buprenorphine program to ensure positive treatment outcomes despite disaster-related factors.

Topics: Analgesics, Opioid; Appointments and Schedules; Benzodiazepines; Bipolar Disorder; Buprenorphine; Cocaine; Cocaine-Related Disorders; Cohort Studies; Comorbidity; Cyclonic Storms; Depressive Disorder; Disaster Planning; Disasters; Female; Health Services Accessibility; Humans; Male; Narcotic Antagonists; New York City; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatient Clinics, Hospital; Prospective Studies; Psychotic Disorders; Risk Factors; Stress Disorders, Post-Traumatic; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion.

Topics: Adolescent; Adult; Alcoholism; Ambulatory Care; Buprenorphine; Cocaine-Related Disorders; Data Interpretation, Statistical; Diagnostic and Statistical Manual of Mental Disorders; Female; Health Personnel; Heroin Dependence; Humans; Income; Length of Stay; Male; Narcotic Antagonists; Patient Compliance; Patient Selection; Pilot Projects; Recurrence; Socioeconomic Factors; Young Adult

Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist-induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction.

Topics: Animals; Buprenorphine; Cocaine; Cocaine-Related Disorders; Male; Naloxone; Naltrexone; Rats; Rats, Wistar; Substance Withdrawal Syndrome

Cocaine use is common in opioid-dependent HIV-infected patients, but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known.. We conducted a prospective study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter. Assessments were conducted at baseline and quarterly for 1 year. We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention, illicit opioid use, antiretroviral adherence, CD4 counts, HIV RNA, and risk behaviors.. Sixty-six percent (197 of 299) of patients reported baseline cocaine use and 65% (173 of 266) of patients with follow-up data reported in-treatment cocaine use. Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention, antiretroviral adherence, CD4 lymphocytes, or HIV risk behaviors. However, baseline cocaine use was associated with a 14.8 (95% confidence interval [CI], 9.0-24.2) times greater likelihood of subsequent cocaine use (95% CI, 9.0-24.2), a 1.4 (95% CI, 1.02-2.00) times greater likelihood of subsequent opioid use, and higher log10 HIV RNA (P < 0.016) over time. In-treatment cocaine use was associated with a 1.4 (95% CI, 1.01-2.00) times greater likelihood of concurrent opioid use.. Given cocaine use negatively impacts opioid and HIV treatment outcomes, interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted.

Topics: Adult; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Risk Factors; Treatment Outcome; Unsafe Sex

Necrosis of the penis glans is commonly described after circumcision or strangulation. We report the case of a patient, opioid abuser, who presented an isolated glans necrosis after an injection of buprenorphin. The buprenorphin (Subutex) is a sublingual partial mu-opioid agonist used for the treatment of heroin dependance. Its intravenous or subcutaneous abuse is associated with local infection. The patient require a surgical intervention. After the failure of a mucosal graft, a soft skin graft was done.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Follow-Up Studies; Heroin Dependence; Humans; Injections, Subcutaneous; Male; Narcotic Antagonists; Necrosis; Penis; Reoperation; Skin Transplantation; Surgical Wound Infection; Wound Healing

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Hand; Heroin Dependence; Humans; Lymph Nodes; Lymphatic Vessels; Lymphedema; Male; Opioid-Related Disorders; Radionuclide Imaging; Substance Abuse, Intravenous

Topics: Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Half-Life; Humans; Male; Middle Aged; Morphine; Pain, Postoperative; Substance-Related Disorders

Addiction to heroin and crack cocaine is debilitating and persistent, but such disorders are treatable. We present the first effectiveness study of the main community interventions for addiction to heroin and crack cocaine in England, using data from the National Drug Treatment Monitoring System (NDTMS).. The study cohort consisted of all adults with a heroin or crack cocaine addiction, or both, who started pharmacological treatment (n=18 428 patients) or psychosocial treatment (n=2647) between Jan 1 and Nov 30, 2008, received at least 6 months' treatment or were discharged by the study endpoint (May 31, 2009), and had outcome data submitted to the NDTMS. Effectiveness was assessed from change in days of heroin or crack cocaine use, or both in the 28 days before the start of treatment and in the 28 days before review.. 14 656 clients-74% of the cohort eligible for analysis at review with available data-were analysed at the study endpoint. During the 28 days before review, 37% (5016/13 542) of heroin users abstained from heroin and 52% (3941/7636) of crack cocaine users abstained from crack cocaine. A higher proportion of users of heroin only abstained than did users of both heroin and crack cocaine (42% [2465/5863] vs 33% [2551/7679]; OR 1.46, 95% CI 1.36-1.56), and more users of crack cocaine only abstained than did users of both drugs (57% [295/522] vs 51% [3646/7114]; 1.24, 1.03-1.48). Overall heroin use reduced by 14.5 days (95% CI 14.3-14.7) and crack cocaine use by 7.7 days (7.5-7.9). For clients given pharmacological treatment, reduction in days of heroin use was smaller for users of both heroin and crack cocaine than for users of heroin alone (p<0.0001), but this differential effectiveness was not recorded for psychosocial treatment in heroin or crack cocaine users compared with users of both drugs.. The first 6 months of pharmacological or psychosocial treatment is associated with reduced heroin and crack cocaine use, but the effectiveness of pharmacological treatment is less pronounced for users of both drugs. New strategies are needed to treat individuals with combined heroin and crack cocaine addiction.. National Treatment Agency for Substance Misuse.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Community Mental Health Services; England; Female; Heroin Dependence; Humans; Linear Models; Male; Methadone; Multivariate Analysis; Narcotic Antagonists; Program Evaluation; Prospective Studies; Psychotherapy; Treatment Outcome

Chronic treatment with the mu-opioid receptor agonist, buprenorphine, reduces cocaine-induced behaviors in rats with a history of cocaine self-administration. The mechanisms underlying these actions of buprenorphine remain unclear.. The objective of this study is to investigate the effects of chronic buprenorphine treatment on cocaine-induced activity and levels of glutamate and dopamine (DA) in the nucleus accumbens (NAc) in rats that were preexposed to cocaine or drug-naïve.. In experiment 1, basal levels of NAc glutamate were assessed using in vivo microdialysis in cocaine-naïve rats that were treated chronically with buprenorphine (3.0 mg/kg per day) via osmotic minipumps or that underwent sham surgery. In experiment 2, rats were preexposed to seven daily injections of cocaine or saline. After a 12-16-day drug-free period, extracellular levels of NAc glutamate and DA and locomotor activity were assessed simultaneously, before and after an acute injection of cocaine (15 mg/kg, intraperitoneal), in rats under sham and chronic buprenorphine (3.0 mg/kg per day) treatment.. Chronic buprenorphine treatment increased basal levels of glutamate in drug-naïve and cocaine-preexposed rats, blocked the expression of locomotor sensitization to cocaine, and potentiated the NAc DA response to acute cocaine in cocaine-preexposed rats.. These findings suggest that buprenorphine may block the expression of cocaine sensitization and other cocaine-related behaviors by increasing basal levels of glutamate in the NAc, which would serve to decrease the effectiveness of cocaine or cocaine-associated cues.

Topics: Animals; Brain Mapping; Buprenorphine; Chromatography, High Pressure Liquid; Cocaine; Cocaine-Related Disorders; Dopamine; Dopamine Uptake Inhibitors; Glutamic Acid; Male; Microdialysis; Motor Activity; Narcotic Antagonists; Nucleus Accumbens; Rats; Rats, Long-Evans

The use of heroin, cocaine, and other drugs is well researched in New York City, but prescription opioids (POs) have been overlooked. This study documents patterns of PO use, misuse, and diversion among street drug users, and begins to indicate how drug culture practices interact with the legitimate therapeutic goals of PO prescriptions (e.g. pain management).. Staff completed interviews inquiring about the reasons for use of POs and illicit drugs with 586 street drug users. Ethnographers wrote extensive field notes about subjects' complex patterns of PO use.. Methadone was used (71.9%) and sold (64.7%) at a higher level than OxyContin, Vicodin, and Percocet, used by between 34% and 38% of the users and sold by between 28% and 41% of the sellers. Recent PO use is associated with the recency of using heroin and cocaine (p<.001). Half of the heroin/cocaine sellers sold POs, and one quarter of the PO sellers only sold POs. Subjects were classified into four groups by whether they diverted POs or used POs to relieve pain or withdrawal rather than for euphoria. This classification was associated with frequency of PO use, whether POs were obtained from doctors/pharmacies or from drug dealers and family members, and those mostly likely to use POs for pain and withdrawal.. POs are an important component of street drug users' drug-taking regimes, especially those who are Physically Ill Chemical Abusers (PICA). Future research is needed to model PO use, misuse, and diversion among this population.

Topics: Administration, Intranasal; Adult; Aged; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Drug Prescriptions; Ethnicity; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; New York City; Pain; Patient Selection; Socioeconomic Factors; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Substance-Related Disorders

For opioid-dependent patients, the need for detoxification has been a barrier to entry into long-term residential treatment. This report describes a retrospective observational cohort study with the first 38 opioid-dependent patients entering First Step, a 14-day buprenorphine-naloxone (Suboxone) detoxification regimen integrated into a long-term residential therapeutic community (TC) program. Eighty-nine percent (34 of 38) of First Step patients completed a 14-day buprenorphine taper protocol, 50% (19 of 38) completed an initial 3- to 4-week stay, and 39% (15 of 38) completed at least 3 months of residential treatment at the TC. Retention did not differ significantly in a demographically matched concurrently admitted control group without impending opioid withdrawal, in which 65% (24 of 37) completed an initial 3- to 4-week stay (p = .20) and 57% (21 of 37) completed at least 3 months of treatment (p = .14). Withdrawal symptoms were mild, and there were no instances of precipitated withdrawal. The findings suggest the potential for buprenorphine to serve as a bridge, improving the viability of long-term residential treatment for managing opioid dependence.

Topics: Adult; Alcoholism; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Long-Term Care; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Neurologic Examination; New York City; Opioid-Related Disorders; Patient Dropouts; Residential Treatment; Retrospective Studies; Substance Withdrawal Syndrome; Therapeutic Community

The mechanisms through which buprenorphine (BUP), a mixed opioid agonist-antagonist, reduces both heroin and cocaine taking remain unclear. Evidence suggests that chronic exposure to BUP blunts drug seeking by attenuating the salience of drug-associated cues. Here, we examined the effect of chronic BUP treatment (osmotic minipumps, 3.0 mg/kg/day) in rats on responding for sucrose pellets and associated cues on FR1, FR5, and PR schedules and on extinction and reinstatement of sucrose seeking by sucrose priming. The effect of chronic BUP treatment on the dopamine (DA) response in the nucleus accumbens (NAc) to sucrose pellets and to lab chow was also measured using in vivo microdialysis. Whereas chronic BUP treatment had only a modest effect on pellet intake on the FR1 schedule, it significantly reduced responding at the outset of sessions and reduced lever pressing during sucrose-associated cue presentations. No effect was observed in the FR5 or PR schedules. BUP slightly reduced responding during extinction and significantly reduced reinstatement. Chronic BUP did not alter the NAc DA response to either sucrose pellets or lab chow, although it did significantly increase basal DA. Consistent with previous studies with heroin and cocaine, chronic BUP reduced responding in the presence of reward-related cues.

Topics: Animals; Buprenorphine; Cocaine-Related Disorders; Cues; Eating; Extinction, Psychological; Heroin Dependence; Male; Narcotic Antagonists; Rats; Rats, Long-Evans; Reinforcement Schedule; Reward; Self Administration; Sucrose

Topics: Alcohol Drinking; Buprenorphine; Cocaine-Related Disorders; Dopamine; Humans; Narcotic Antagonists; Nociceptin; Nociceptin Receptor; Nucleus Accumbens; Opioid Peptides; Receptors, Opioid

Hepatitis C virus (HCV) is the most prevalent chronic viral illness in the United States. Many individuals with virus HCV are opioid dependent requiring treatment with opiate substitution treatment such as buprenorphine. Previous reports in the literature have suggested hepatotoxicity with buprenorphine tempering initial enthusiasm of the safety of buprenorphine in HCV-infected patients.. As part of an ongoing SAMHSA-funded grant to expand opiate substitution therapy with buprenorphine, all opioid-dependent patients seeking treatment with buprenorphine undergo a laboratory evaluation including transaminases (AST/ALT) as well as laboratory evaluation for acute and chronic hepatitis.. Of the 121 patients screened for entry into buprenorphine treatment, 4 patients had evidence of acute HCV infection.. Despite markedly elevated transaminases in the setting of acute hepatitis C infection, these patients tolerated buprenorphine treatment with improvement in their transaminases during the course of buprenorphine treatment.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Bipolar Disorder; Buprenorphine; Cocaine-Related Disorders; Female; Hepatitis B virus; Hepatitis C; Humans; Liver; Liver Function Tests; Male; Naloxone; Narcotic Antagonists; Needle Sharing; Opioid-Related Disorders; RNA, Viral; Transaminases

Naltrexone treatment has demonstrated some advantages for special populations of heroin addicted individuals, but patients' compliance seems to be very poor, with a low adherence and low retention rate. Kappa-opioid system overdrive seems to contribute to opioid protracted abstinence syndrome, with dysphoria and psychosomatic symptoms during naltrexone treatment. The objective of this observational study was to determine the effectiveness of a functional k antagonist in improving naltrexone treatment outcome. A partial mu agonist/kappa antagonist (buprenorphine) and a mu antagonist (naltrexone) were combined during a 12 weeks protocol, theoretically leaving k antagonism as the major medication effect. Sixty patients were submitted to outpatient rapid detoxification utilizing buprenorphine and opioid antagonists. Starting on the fifth day, 30 patients (group A) received naltrexone alone. Alternatively, 30 patients (group B) received naltrexone (50mg oral dose) plus buprenorphine (4 mg sublingual) for the 12 weeks of the observational study. The endpoints of the study were: retention in treatment, negative urinalyses, changes in psychological symptoms (Symptom Checklist-90 Revised: SCL-90) and craving scores (visual analysis scale (VAS)). Thirty-four subjects (56.67%) completed the 12 weeks study. Twenty-one patients (35.0%) had all urine samples negative for opiates and cocaine. nine subjects (15.0%) had urine samples negative for cocaine and opiates for the last 4 weeks of the study. five subjects (8.3%) continued to use cocaine during the 12 weeks of the study. No significant change in pupillary diameter after buprenorphine administration was evidenced during clinical observations from baseline across the weekly measurements. Retention rates in group A (naltrexone) and group B (naltrexone + buprenorphine) at week 12 were respectively 40% (12 patients) and 73.33% (22 patients), with a significant difference in favour of group B (p= 0.018). Patients treated with naltrexone in combination with buprenorphine (B patients) showed a significantly lower rate of positive urines for morphine (4.45%) and cocaine metabolites (9.09%) than those treated with naltrexone alone (A) (25%, morphine; 33.33% cocaine) (p< 0.05; p< 0.05). Irritability, depression, tiredness, psychosomatic symptoms and craving scores decreased significantly less in Group A patients than in group B patients. The dysfunction of opioid system with kappa receptors hyper-activation provoked by heroi

Topics: Adult; Affect; Buprenorphine; Cocaine; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Liver; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Psychiatric Status Rating Scales; Substance Abuse Detection; Survival Analysis

This study of a cohort of drug addicts receiving buprenorphine maintenance treatment in a district in western France focused on changes in their drug use and their social and work lives. It also looked at the health consequences of their drug use before and after maintenance treatment (mean: four years).. From the files of an agency providing services to drug addicts, we randomly selected 180 of the 236 patients receiving buprenorphine maintenance treatment (BMT). Usable questionnaires were returned by 118 subjects (66% response rate). This self-administered questionnaire included 32 items.. The respondents accounted for half the population receiving drug maintenance treatment and were representative of the population for age and sex. The mean age was 30 +/- 5 years, mean BMT dose 6,5 mg/day, and mean duration of drug maintenance treatment 47 +/- 27 months. Other drug use diminished during the four years of maintenance treatment: three of every four heroin users had stopped, opiate users dropped from 31% to 5% of the population, and cocaine use followed a similar trend. Benzodiazepine use also fell, but remained relatively frequent (27%, compared with 68% four years earlier). Drinking patterns changed from strongly alcoholic beverages to lower-proof drinks. Arrest rates dropped from 70% to 25%. The percentage of persons seropositive for HIV (4%) and HCV (33%) remained low, but too many subjects had not been screened (35%). Roughly 10% of these subjects had returned to work, mainly those who had cut their drug use most.. While our survey reveals some positive points, especially a reduction in illegal drug use, several negative observations appeared, including combined use of cannabis and benzodiazepines, inadequate screening, and misuse of BMD. These results underline how important it is for care providers to focus simultaneously on medical treatment and identification of co-morbidities and to provide social work when necessary. The employment rate remains too low.

Topics: Adult; Behavior, Addictive; Benzodiazepines; Buprenorphine; Cocaine-Related Disorders; Cohort Studies; Employment; Female; France; Heroin Dependence; HIV Seropositivity; Humans; Male; Marijuana Abuse; Narcotic Antagonists; Opioid-Related Disorders; Socioeconomic Factors; Substance-Related Disorders; Surveys and Questionnaires; Time Factors

Topics: Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Counseling; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance

A 37-year-old man with a 19-years history of injection drug use (IDU) who had acquired a chronic hepatitis C virus (HCV-) infection 9 years ago, entered the German clinical study on heroine assisted treatment ("Modellprojekt zur heroingestützten Behandlung Opiatabhängiger"). Before study onset he received buprenorphine maintainance treatment, while at the same time engaging in illicit IDU (heroine, cocaine). He lived in a caravan and was on social welfare.. PCR revealed a genotype 2 and an HCV-viral load of 310,000 IU/ml. Liver biopsy showed a moderate chronic active hepatitis and a mild portal fibrosis without signs of liver cirrhosis.. Within the heroine-assisted treatment program the patient injected heroine under medical supervision several times a day and attended the standardized psychosocial program that comprised an intensive education on HCV-infection. Within a period of ten months of physical and social stabilization he managed to stop illicit drug use, found stable housing and started to work. We then initiated treatment of HCV-infection. Subcutaneous pegylated interferon alpha-2a, peroral ribavirin and intravenous heroine were administered as directly observed therapy. Based on the close mashed care of the heroine assisted treatment setting, side effects were well controllable and reversible after the end of antiviral therapy. A sustained response was obtained.. After careful indication, heroine-assisted treatment with particularly intensive medical and psychological care can offer appropriate conditions for a save and successful treatment of hepatitis C as well as for a sustained result.

Topics: Administration, Oral; Adult; Antiviral Agents; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Comorbidity; Drug Therapy, Combination; Hepatitis C, Chronic; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Male; Polyethylene Glycols; Recombinant Proteins; Rehabilitation, Vocational; Ribavirin; Social Adjustment; Social Welfare; Substance Abuse, Intravenous

Topics: Adult; Buprenorphine; Cocaine; Cocaine-Related Disorders; Female; Humans; Narcotic Antagonists; Trichotillomania

With the recent approval of buprenorphine for the treatment of opiate dependence in the United States it has become important to develop an understanding of the factors that influence the likelihood of successful treatment outcomes when using buprenorphine. This study examined, in a convenience sample, the relationship between novelty-seeking behaviors, as determined by Cloninger's Tridimensional Personality Questionnaire (TPQ), and attendance variables during participation in a buprenorphine-based treatment program for 21 heroin-dependent cocaine users that took place in the late 1990s. Approximately two-thirds of the participants were male and primarily African-American. About half of them were employed and had at least a high school education. Approximately one-third of them were married or cohabitating and they all resided in the greater Detroit, Michigan area of the United States. The Tridimensional Personality Questionnaire (TPQ) was administered to the participants prior to entering the treatment program. Demographic variables, psychiatric distress, and substance use severity were also evaluated. Variables with significant bivariate relationships with poor attendance measures were entered into a regression analysis predicting attendance measures. Participants who scored high on the TPQ Novelty Seeking Scale attended significantly fewer regularly scheduled visits, had a greater overall number of missed visits, and shorter treatment retention times. Demographics, substance use severity, and psychiatric distress did not have significant relationships with these attendance measures.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Humans; Likelihood Functions; Middle Aged; Narcotic Antagonists; Outpatients; Patient Compliance; Personality Inventory; Surveys and Questionnaires

Buprenorphine was approved in France for treating opiate dependence in July 1995 and can be prescribed by general practitioners (GPs). Most studies assessing buprenorphine maintenance treatment (BMT) outcomes have taken place in GP settings. An evaluation of BMT outcomes in patients already followed for their HIV-infection could supply additional information about the changes in addictive practices in a non-GP setting.. We assessed BMT discontinuations and the course of self-reported addictive behaviours and characteristics associated with buprenorphine-injection misuse in 114 HIV-infected patients on BMT who were followed in a hospital-based outpatient department.. The continuous series of follow-up visits at which these 114 patients reported regular buprenorphine prescriptions accounted for 237.5 person-years of observation, i.e. 475 follow-up visits. Of the 114 patients on BMT, 43% continued BMT throughout the follow-up, 40% stopped it, and results for 17% were not available either because they did not answer the self-administered questionnaire (5%) or because they were lost to follow-up (12%). Addictive behaviours declined but buprenorphine injection misuse remained stable. Depression measured by the CESD score (RR=1.04 95%CI [1.01-1.06]), cocaine use (RR=2.48 95%CI [1.31-4.68]) and alcohol consumption exceeding 4 alcohol units (AU) per day (RR=2.29, 95%CI [1.17-4.46]) were independently associated with buprenorphine injection misuse among stabilised BMT patients.. Despite the reduction in drug injection after starting BMT, buprenorphine injection misuse mainly involves patients with characteristics of severe addiction. Better monitoring of the illicit drug use patterns of patients on BMT may suggest new medical strategies for GPs to improve BMT outcomes.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Cohort Studies; Depression; Female; Follow-Up Studies; Heroin Dependence; HIV Seropositivity; Humans; Injections, Intravenous; Male; Narcotic Antagonists; Severity of Illness Index; Substance Abuse, Intravenous; Surveys and Questionnaires; Treatment Refusal

This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant relationships with overall retention were entered into a logistic regression analysis. In addition, using a survival analysis, all variables with significant relationships with time to drop-out were entered into a multivariate proportional hazards regression with time dependent covariates. Results demonstrated that although high novelty seekers, in comparison to low novelty seekers, were more likely to drop-out by the end of treatment, they had higher retention rates during the early phases of treatment. It is suggested that buprenorphine and contingency management were viewed by participants as novel treatment components and thus facilitated high novelty seekers' success early in treatment. If replicated, results suggest that inclusion of novel treatment components might facilitate retention among this at-risk group.

Topics: Adult; Age Factors; Buprenorphine; Chi-Square Distribution; Cocaine-Related Disorders; Confidence Intervals; Exploratory Behavior; Female; Heroin Dependence; Humans; Logistic Models; Male; Middle Aged; Narcotics; Patient Dropouts; Survival Analysis; Treatment Outcome

The simultaneous intravenous (i.v.) administration of heroin and cocaine, called a "speedball," is often reported clinically, and identification of effective pharmacotherapies is a continuing challenge. We hypothesized that treatment with combinations of a dopamine reuptake inhibitor, indatraline, and a mu partial agonist, buprenorphine, might reduce speedball self-administration by rhesus monkeys more effectively than either drug alone. Speedballs (0.01 mg/kg/inj cocaine + 0.0032 mg/kg/inj heroin) and food (1 g banana pellets) were available in four daily sessions on a second-order schedule of reinforcement [fixed ratio (FR)4; variable ratio (VR)16:S]. Monkeys were treated for 10 days with saline or ascending dose combinations of indatraline (0.001-0.032 mg/kg/day) and buprenorphine (0.00032-0.01 mg/kg/day). Two combinations of indatraline (0.32 and 0.56 mg/kg/day) + buprenorphine (0.10 and 0.18 mg/kg/day) significantly reduced speedball self-administration in comparison to the saline treatment baseline (p <.01-.001), whereas the same doses of each compound alone had no significant effect on speedball-maintained responding. Daily treatment with 0.56 mg/kg/day indatraline + 0.18 mg/kg/day buprenorphine produced a significant downward shift in the speedball dose-effect curve (p <.01) and transient changes in food-maintained responding. These findings suggest that medication mixtures designed to target both the stimulant and opioid component of the speedball combination may be an effective approach to polydrug abuse treatment.

Topics: Animals; Buprenorphine; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Interactions; Female; Heroin; Heroin Dependence; Indans; Macaca mulatta; Male; Methylamines; Narcotics; Neurotransmitter Uptake Inhibitors; Self Administration

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Heroin Dependence; Humans; Male; Office Visits; Private Practice; Psychiatry

We compared outcomes for agonist-maintained patients with combined opioid and cocaine dependence who were treated in an earlier clinical trial with group drug counseling (DC; n = 57) or in a current trial with the Community Reinforcement Approach (CRA; n = 60). The association between engagement in nondrug-related activities and abstinence was also evaluated. There were no significant differences between the treatments in retention or drug use. The total number of hours and average hours per week engaged in nondrug-related activities was significantly higher for CRA-treated patients who achieved abstinence from opioids, cocaine, or both combined than for those who never achieved abstinence. Although CRA was not more effective overall than DC, the finding that engagement in reinforcing community activities unrelated to drug use (e.g., planned pleasurable events or parenting activities) was associated with abstinence suggests that the planning and reinforcement of specific nondrug-related social, vocational, and recreational activities is a crucial component of CRA.

Topics: Adult; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Community Networks; Counseling; Female; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Recurrence; Social Support; Socioenvironmental Therapy; Temperance; Treatment Outcome; United States

Topics: Buprenorphine; Cocaine-Related Disorders; Disulfiram; Humans

Buprenophrine is a synthetic opioid with micro-agonist properties currently pending Food and Drug Administration (FDA) approval as a maintenance agent for treating heroin-addicted individuals. Unlike methadone, a widely used opioid maintenance agent, buprenorphine is a kappa-receptor antagonist. Research linking the effects of acupuncture to the release of dynorphin, the endogenous ligand for the kappa-receptor, raised the possibility that buprenorphine may block acupuncture's effects. In this study, we sought to gather preliminary data on this issue in order to guide the clinical care of cocaine-abusing, buprenorphine-maintained patients.. Between-group analysis comparing buprenorphine- and methadone-maintained patients on ratings of acute effects after a single session of auricular acupuncture.. Thirty-four (34) cocaine-abusing, opioid-dependent patients, eighteen (18) maintained on buprenorphine, and sixteen (16) maintained on methadone.. A single, 40-minute session of auricular acupuncture; four needles were inserted in each auricle.. Acute effect ratings in four domains: pain, de qi sensations, relaxation effects, subjective experiences.. There were no significant differences in acute-effects ratings between the two groups. Patients in both groups reported positive effects.. These preliminary findings are consistent with the interpretation that buprenorphine does not block auricular acupuncture, supporting the provisional recommendation that cocaine-abusing patients maintained on buprenorphine should not be excluded from receiving auricular acupuncture or from participating in clinical studies of this treatment modality. Further, controlled research on this issue, with clinical outcomes, is needed.

Topics: Acupuncture, Ear; Adult; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Female; Humans; Male; Methadone; Substance Abuse Treatment Centers; Treatment Outcome

Theoretical considerations as well as pre-clinical data suggest a potential role for glutamate-inhibiting agents in the treatment of cocaine addiction. At present, however, there is little clinical data to inform the use of these agents for this application. In this preliminary study eighteen HIV-seropositive cocaine dependent, opiate-agonist maintained patients received lamotrigine (300 mg/day), an indirect glutamate release inhibitor, on either a standard (n = 8) or accelerated (n = 10) induction schedule for 12 weeks. Results showed a significant decrease in percentage of cocaine-positive urine screens in the standard induction lamotrigine group but not in the accelerated induction group. There were fewer reports of side-effects and fewer dropouts in the standard-induction lamotrigine group compared to the accelerated induction group. Neuropsychological assessments suggested a decrement in the Trail Making Tests, but no other decreases in cognitive functioning. We conclude that standard-induction lamotrigine warrants further investigation for the treatment of cocaine abuse in this patient population.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Female; HIV Seropositivity; Humans; Lamotrigine; Male; Methadone; Middle Aged; Neuropsychological Tests; Psychotherapy, Group; Substance Abuse Detection; Substance Abuse, Intravenous; Treatment Outcome; Triazines