Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population

CONTEXT: No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy. OBJECTIVE: To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals. DESIGN: This 25-week, placebo-controlled, double-blind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB). SETTING: Outpatient clinic at the Veterans Affairs Connecticut Healthcare System. PARTICIPANTS: A total of 106 opiate-dependent, cocaine-abusing individuals. INTERVENTIONS: All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study. MAIN OUTCOME MEASURE: Thrice-weekly urine toxicologic test results for cocaine and heroin. RESULTS: Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (P<.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (P<.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P<.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use. CONCLUSION: These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone.     

A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence

BACKGROUND: This study compared 2 psychosocial approaches for the treatment of cocaine dependence: contingency management (CM) and cognitive-behavioral therapy (CBT). METHODS: Patients with cocaine dependence who were receiving methadone maintenance treatment (n = 120) were randomly assigned to 1 of 4 conditions: CM, CBT, combined CM and CBT (CBT + CM), or treatment as usual (ie, methadone maintenance treatment program only [MMTP only]) (n = 30 per cell). The CM procedures and CBT materials were comparable to those used in previously published research. The active study period was 16 weeks, requiring 3 clinic visits per week. Participants were evaluated during treatment and at 17, 26, and 52 weeks after admission. RESULTS: Urinalysis results during the 16-week treatment period show that participants assigned to the 2 groups featuring CM had significantly superior in-treatment urinalysis results, whereas urinalysis results from participants in the CBT group were not significantly different than those from the MMTP-only group. At week 17, self-reported days of cocaine use were significantly reduced from baseline levels for all 3 treatment groups but not for the MMTP-only group. At the 26-week and 52-week follow-up points, CBT participants showed substantial improvement, resulting in equivalent performance with the CM groups as indicated by both urinalysis and self-reported cocaine use data. CONCLUSIONS: Study findings provide solid evidence of efficacy for CM and CBT. Although the effect of CM is significantly greater during treatment, CBT appears to produce comparable long-term outcomes. There was no evidence of an additive effect for the 2 treatments in the CM + CBT group.     

Heroin and cocaine co-use in a group of injection drug users in Montréal

OBJECTIVE: To describe the pattern of co-use of heroin and cocaine in individuals who were not receiving methadone maintenance treatment. DESIGN: Structured interviews. SETTING: Community hospital. PARTICIPANTS: Individuals (n = 1111) selected from a cohort of out-of-treatment injection drug users in Montréal, Que. OUTCOME MEASURE: Frequency (injections per day) and quantity (number of days of use) of heroin, cocaine and speedball (the simultaneous administration of heroin and cocaine) use reported in the month preceding the interview. RESULTS: About 50% of the sample reported using only cocaine intravenously (C group), about 8% reported using only heroin (H group) intravenously and about 15% reported using both heroin and cocaine (HC group) intravenously. Reported cocaine consumption was similar in the HC and C groups. Heroin was used on fewer days by the HC than by the H group, but the number of injections per day was similar. Speedball use, which was quantified independently from heroin and cocaine use, was reported almost exclusively by the HC group, and speedball was used less often than either heroin or cocaine alone. Finally, a similar proportion of individuals in the C and the HC groups consumed alcohol in the 24 hours preceding the interview, but a larger proportion of individuals in the HC group reported the use of marijuana. CONCLUSION: In a cohort of injection drug users in Montréal, cocaine was the most prevalent illicit drug. Furthermore, about 70% of the heroin users also injected cocaine, but not in the form of speedball. Thus, the sequential co-use of heroin and cocaine is highly prevalent in Montréal and deserves particular clinical attention.     

Fluoxetine treatment of cocaine abuse in heroin addicts

The authors administered fluoxetine to 11 cocaine-abusing heroin addicts entered in a methadone maintenance program to determine whether it would decrease cocaine craving and use. Three patients discontinued treatment within a few days of initiation because of lack of any acute therapeutic effect. The remaining 8 received fluoxetine for at least 1 week and were followed up over 1 to 6 months. Of these 8, 5 (63%) were successfully treated for cocaine abuse. Three case examples are presented. Fluoxetine may prove a useful addition to the therapeutic armamentarium in the treatment of cocaine abuse.     

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone

BACKGROUND: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial

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

Influence of antisocial personality subtypes on drug abuse treatment response

This methodological study examined the impact of antisocial personality disorder (APD) and other psychiatric comorbidity on drug use and treatment retention in 513 new admissions to methadone maintenance treatment. Patients were classified into one of four groups: APD ONLY, APD plus other psychiatric disorder (APD MIXED), other psychiatric disorder, and no psychiatric disorder. Patients completed research assessments and were then followed for 1 year of treatment. Patients with APD had longer histories of heroin and cocaine use than non-APD patients and were more likely to meet criteria for cocaine dependence. Distinct clinical profiles emerged that differentiated APD ONLY from APD MIXED. APD ONLY patients exhibited higher rates of cocaine and heroin use, whereas those with APD MIXED exhibited higher rates of benzodiazepine use. Self-report measures supported urinalysis results, but group differences did not affect treatment retention. These differences in clinical profiles should be considered when evaluating treatment performance in substance abusers with APD.     

Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance

BACKGROUND: Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. METHODS: Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). RESULTS: Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. CONCLUSIONS: In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.     

Alternative induction and crossover schedules for methadyl acetate

Various schedules exist for inducting heroin addicts newly admitted to treatment into methadyl acetate maintenance and crossover schedules for the transition from methadone maintenance to methadyl acetate maintenance. A sample of 255 street addicts was randomized to three induction schedules: methadyl acetate three times a week (tiw) with placebos on alternate days; methadyl acetate tiw supplemented with decreasing doses of methadone on alternate days; methadyl acetate six days a week with diminishing doses on three days. Treatment was double-blind for four weeks and single-blind for six. All schedules were considered feasible, but supplementation with methadyl acetate or methadone had no advantage. A sample of 310 patients receiving methadone maintenance was randomized to comparable supplementation groups, except that the group receiving supplementary methadyl acetate received it along with the regular dose. This schedule was not successful. Supplementing with methadone had no advantage.     

Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues

OBJECTIVE: Environmental drug-related cues have been implicated as a cause of illicit heroin use during methadone maintenance treatment of heroin dependence. The authors sought to identify the functional neuroanatomy of the brain response to visual heroin-related stimuli in methadone maintenance patients. METHOD: Event-related functional magnetic resonance imaging was used to compare brain responses to heroin-related stimuli and matched neutral stimuli in 25 patients in methadone maintenance treatment. Patients were studied before and after administration of their regular daily methadone dose. RESULTS: The heightened responses to heroin-related stimuli in the insula, amygdala, and hippocampal complex, but not the orbitofrontal and ventral anterior cingulate cortices, were acutely reduced after administration of the daily methadone dose. CONCLUSIONS: The medial prefrontal cortex and the extended limbic system in methadone maintenance patients with a history of heroin dependence remains responsive to salient drug cues, which suggests a continued vulnerability to relapse. Vulnerability may be highest at the end of the 24-hour interdose interval.     

Neuropsychological Status of Heroin Users Undergoing Methadone Maintenance in Harm Reduction Program and Therapeutic Community

The neuropsychological consequences of opioid abuse are particularly evident in attention, memory and executive functioning, but it remains unclear whether these consequences persist in heroin users doing methadone in harm reduction programs and therapeutic community treatments. Thus, the current study aimed to assess these cognitive domains in distinct clinical groups of heroin users undergoing methadone maintenance. The sample consisted of 110 participants divided in four groups (low threshold methadone program, short-term community treatment, long-term community treatment, drug-free controls). These groups were compared regarding memory and attentional abilities. Multiple linear regressions were then conducted to obtain standardized effect sizes for significant comparisons. Results showed a better attentional and memory function in patients that were in opioid dependence treatment in community opposed to patients in harm reduction programs (p’s?<?0.05). Standardized effect sizes suggest larger improvements in cognition in long-term heroin-abstinent individuals doing methadone maintenance. These results highlight the detrimental effect of heroin use in cognitive function, but also suggest that this decrement may be reversed during long-term opioid dependence treatment.     

Does naltrexone treatment lead to depression? Findings from a randomized controlled trial in subjects with opioid dependence

OBJECTIVE: Dysphoria and depression have been cited as side effects of the opioid antagonist naltrexone. We aimed to assess whether depressive symptoms are a clinically relevant side effect in a population receiving naltrexone as a treatment for opioid dependence. METHODS: We carried out a randomized controlled, open-label trial comparing rapid opiate detoxification under anesthesia and naltrexone treatment with continued methadone maintenance at the Alcohol and Drug Service, Royal Brisbane and Women's Hospital, Brisbane, Australia. The study subjects were patients stabilized on methadone maintenance treatment for heroin dependence who wished to transfer to naltrexone treatment. The Beck Depression Inventory, State-Trait Anxiety Inventory and Opiate Treatment Index subscales for heroin use and social functioning were used at baseline and follow-up assessments at 1, 2, 3 and 6 months. RESULTS: Forty-two participants were allocated to receive naltrexone treatment, whereas 38 continued methadone maintenance as the control condition. Participants who received naltrexone did not exhibit worsening of depressive symptoms. In participants attending all follow-up assessments, there was a trend for those receiving naltrexone to exhibit an improvement in depression over time compared with the control group. Participants who were adherent to naltrexone treatment exhibited fewer depressive symptoms than those who were nonadherent. CONCLUSIONS: These results suggest that depression need not be considered a common adverse effect of naltrexone treatment or a treatment contraindication and that engaging with or adhering to naltrexone treatment may be associated with fewer depressive symptoms.     

行为列联管理在美沙酮维持治疗者中的疗效:一项随机对照研究(英文)

背景为了应对海洛因依赖的严重后果,我国开展了美沙酮维持治疗(methadone maintenance treatment,MMT)项目,但是MMT依从性差。目的评估在美沙酮维持治疗中行为列联管理(contingency management,CM)对阿片类药物依赖者的作用。假设在上海市常规MMT项目基础上结合以奖励机制为基础的CM干预共12周,可提高MMT治疗依从性和增加操守程度。方法来自于3个自愿戒毒MMT门诊的160名海洛因依赖者被随机分入常规治疗组(MMT,n=80)和干预组(MMT+CM,n=80),在前12周每周评估患者的服药行为并进行尿液的毒品检测,随后在第16、20和24周分别进行上述评估检测。结果干预组和常规治疗组完成12周治疗的比例都很高,分别为87.5%和86.2%。12周中,两组服用美沙酮的平均天数差异无统计学意义[70(2.9)d与71(2.7)d],两组未吸海洛因的最长时间(分别为7.4周与6.5周)以及尿检阴性的次数(分别为7.9次与7.6次)也没有明显差异。同样,根据24周的分析提示两组间差异也无统计学意义。用成瘾严重程度指数评估成瘾程度,24周内两组完成随访者的成瘾严重程度都显著下降,但是两组间比较同样无明显差异。结论在我国上海的MMT门诊,以奖励机制为基础的行为列联管理干预并未起到提高治疗依从性和促进保持操守的作用。这与西方研究结果不同。究其原因,一是基线依从性高(86%),二是CM项目提供的奖励相对少。在CM项目中奖励是与场景相关的,因而需要对场景进行仔细的分析,了解在特定场景采用什么特定的奖励措施,以便鼓励目标人群改变行为。     

Naltrexone in the treatment of heroin dependence: relationship with depression and risk of overdose

OBJECTIVE: This article examines the use of naltrexone in the treatment of heroin dependence. The relationship between naltrexone and depression as well as risk of overdose is examined. METHOD: The existing literature is reviewed along with recent interim data from clinical trials underway in Victoria. RESULTS: Naltrexone is a recent addition to treatment for heroin dependence in Australia. The relationship between depression and naltrexone has been examined in previous literature. Underlying rates of depression in heroin users are high and treatment may resolve or exacerbate depression. Research to date demonstrates that the addition of naltrexone does not necessarily increase depression in patients. The risk of non-fatal heroin overdose is significantly elevated after naltrexone treatment as a result of reduced tolerance. Data from clinical trials underway in Victoria demonstrate a significantly elevated rate of non-fatal overdose in naltrexone patients compared to those in substitution maintenance treatment. The mortality rate subsequent to naltrexone treatment appears to be equivalent to or greater than that for untreated heroin users. Further research is required. CONCLUSIONS: Clinicians need to carefully monitor depression in patients, and warn patients of the risks of reduced tolerance to opiates following naltrexone treatment. Agonist treatments such as methadone, LAAM and buprenorphine carry much less risk of overdose.     

Predicting Outcome in Public Addiction Services Using Data Collected During Routinely Assessment Procedures

The study examined the ability of several baseline variables to predict retention and treatment outcome in a cohort study that included 137 participants with heroin and cocaine addiction attending a public addiction service in Italy. Predictors included past drug use, intravenous use, initial urine drug screen results, cocaine and heroin craving and self-reported psychiatric symptoms. Severe depression and, in a lesser extent, anxiety symptoms, predicted lower retention. Only intravenous use was a significant predictor of cocaine use in the whole sample. Positive urine for cocaine and intravenous use predicted worse outcome among heroin addicts. Three Symptoms Checklist-90 (SCL-90) scales scores were associated with lower cocaine and heroin use. Multiple logistic regression showed that cocaine positivity and more structured psychosocial treatment predicted successful outcome. Results highlight the prognostic value of carefully assessing patterns of cocaine use and co-use, routes of administration and psychiatric symptoms at the beginning of treatment, especially in heroin addicts.     

Risk factors for criminal recidivism -- a prospective follow-up study in prisoners with substance abuse

ABSTRACT: BACKGROUND: Substance use in general has been shown to predict criminal recidivism. The present study aimed to examine potential predictors of criminal recidivism, including substance-specific substance use patterns, in prisoners with substance use. METHODS: A cohort of prisoners with substance use problems (N = 4,152) were assessed with the Addiction Severity Index (ASI) in the Swedish criminal justice system. Clients were followed for an average of 2.7 years. Criminal recidivism was defined as any return to the criminal justice system. RESULTS: During follow-up, 69 percent (n = 2,862) returned to the criminal justice system. Recidivism was associated with amphetamine and heroin use, with an additive risk for injectors, and with polysubstance use. Also, recidivism was negatively associated with alcohol, other opioids than heroin/methadone and with hallucinogenic drugs, and positively associated with previous psychiatric in-patient treatment, violent behaviour, and with a shorter index sentence. Associations remained when controlling for type of crime. CONCLUSIONS: Even when controlling for type and severity of crime, and for psychiatric problems, risk of criminal relapse was increased by substance use variables, including amphetamine, heroin and polysubstance use, and an additional risk was shown for injection drug users. These findings have implications for the need for substance abuse treatment after release from prison.     

Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial

CONTEXT: Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users. OBJECTIVES: To compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies-cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)-in reducing cocaine use. DESIGN: Randomized, placebo-controlled, double-masked (for medication condition), factorial (2 x 2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT. SETTING: A community-based outpatient substance abuse treatment program. PATIENTS: A total of 121 individuals meeting the criteria for current cocaine dependence. INTERVENTIONS: Patients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks. MAIN OUTCOME MEASURES: Random regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens. RESULTS: Participants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT (P<.01 for both). Findings were consistent across all study samples (eg, intention to treat, treatment initiators, and treatment completers). Benefits of disulfiram use and CBT were most pronounced for participants who were not alcohol dependent at baseline or who fully abstained from drinking alcohol during treatment. Adverse effects experienced by participants who received disulfiram were mild and were not considerably different from those experienced by participants who received placebo. CONCLUSIONS: Disulfiram and CBT are effective therapies for general populations of cocaine-dependent individuals. Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use.     

Nonnarcotic drug use over an addiction career--a study of heroin addicts in Baltimore and New York City

Detailed interview data from 250 male narcotic addicts attending methadone maintenance treatment centers in Baltimore and New York City were used to confirm and extend previous findings regarding the frequency of nonnarcotic drug abuse among relevant addict subgroups. Consistent with earlier results, abuse of nonnarcotic drugs in general, and particularly cocaine, was higher during periods of addiction than during periods of nonaddiction. Overall, marijuana and cocaine were the two main drugs of abuse, but variations were present according to addiction status period, city, and ethnic group membership. Relationships between cocaine use and specific types of criminal activity were also examined. It was found that there were high associations between cocaine use and several different kinds of crime.     

Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use

BACKGROUND: This screening trial evaluated whether the GABAB agonist baclofen demonstrated sufficient clinical efficacy to recommend an adequately powered trial of the medication as a pharmacotherapy for cocaine dependence. METHOD: Participants with cocaine dependence verified by the Structured Clinical Interview for DSM-IV were randomly assigned to baclofen (N = 35; 20 mg t.i.d.) or placebo conditions (N = 35; identical in appearance and dosage rate) using a 2-group, experimental, 16-week double-blind design featuring thrice-weekly cognitive-behavioral drug counseling groups. Outcomes were retention, cocaine use, cocaine craving, and adverse events. RESULTS: A generalized estimating equation (GEE) model showed that participants assigned to receive baclofen demonstrated statistically significant reductions in cocaine use over those assigned to receive placebo as indicated by urine drug screening results (chi(2) = 5.34, df = 1, p =.021). Confirming the GEE model, longitudinal analyses showed that participants assigned to receive baclofen demonstrated significant and stepwise increases in the probability of providing benzoylecgonine-free urine samples throughout the trial as the number of benzoylecgonine-positive samples increased during baseline (chi(2) = 10.63, df = 1, p =.001). Participants assigned to placebo demonstrated no such association. Univariate analyses of aggregates of urine drug screening showed generally favorable outcomes for baclofen, but not at statistically significant levels. There was no statistical significance observed for retention, cocaine craving, or incidence of reported adverse events by treatment condition. CONCLUSIONS: Project findings demonstrated initial clinical efficacy of baclofen over placebo in reducing cocaine use when delivered concurrent with thrice-weekly drug abuse counseling sessions. The effects of baclofen were particularly apparent for those participants with chronic levels of cocaine use at baseline and provide support for a full-scale efficacy trial for baclofen, especially among this subgroup of patients.