Naltrexone treatment of comorbid alcohol and cocaine use disorders

 Naltrexone (NTX) has been shown to be efficacious for the treatment of alcohol dependence. Since alcohol and cocaine use disorders commonly co-occur, we conducted a randomized, double-blind, placebo-controlled trial of NTX 50 mg/day in 64 subjects with comorbid alcohol and cocaine use disorders. Although subjects in both groups reduced their consumption of both alcohol and cocaine during the 8-week trial, there was no consistent advantage to NTX over placebo treatment. We conclude that, due to behavioral, neurochemical, or other factors, individuals with both alcohol and cocaine use disorders are distinct from those dependent on alcohol alone, and that NTX at a dosage of 50 mg/day is not efficacious in this patient population. Several factors, including medication dosage, length of treatment, sample size and attrition rate, limit the interpretation of these findings. Consequently, we recommend that subsequent trials of NTX to reduce the risk of relapse in patients with comorbid alcohol and cocaine use disorders take these issues into account. Received: 15 November 1997 / Final version: 9 May 1998     

Fluoxetine treatment of cocaine-dependent patients with major depressive disorder.

Sixty-eight male and female individuals with both DSM-IV diagnoses of cocaine dependence and major depressive disorder were randomly assigned to one of two medication conditions (placebo vs. 40 mg per day) as part of a double-blind, placebo-controlled clinical efficacy trial of fluoxetine for the treatment of this dual diagnosis. During the 12-week outpatient treatment phase all participants also received individual cognitive-behavioral psychotherapy targeting both cocaine use and depression. Depressive symptoms remitted as a function of time in treatment, with no significant medication effects found. Fewer cocaine positive urines were found during the first 6 weeks of treatment in the placebo group compared with the 40-mg group. Cocaine use and depressive symptoms during treatment were significantly correlated. The findings fail to support the role of fluoxetine for treatment of cocaine use and depression in dually-diagnosed patients.     

Effects on smoking cessation: naltrexone combined with a cognitive behavioral treatment based on the community reinforcement approach

A promising option in substance abuse treatment is the Community Reinforcement Approach (CRA). The opioid antagonist naltrexone (NTX) may work in combination with nicotine replacement therapy (NRT) to block the effects of smoking stimuli in abstinent smokers. Effects of lower doses than 50 mg/dd. have not been reported. A study was conducted in Amsterdam in 2000/2001 with the objective to explore the effects of the combination NTX (25/50-mg dd.), NRT, and CRA in terms of craving and abstinence. In a randomized open label, 2 x 2 between subjects design, 25 recovered spontaneous pneumothorax (SP) participants received 8 weeks of treatment. Due to side effects, only 3 participants were compliant in the 50-mg NTX condition. Craving significantly declined between each measurement and there was a significant interaction between decline in craving and craving measured at baseline. The abstinence rate in the CRA group was nearly double that in the non-psychosocial therapy group (46% vs. 25%; NS) at 3 months follow-up after treatment.     

A comparison between low-magnitude voucher and buprenorphine medication contingencies in promoting abstinence from opioids and cocaine

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.     

Effects on Smoking Cessation: Naltrexone Combined with a Cognitive Behavioral Treatment Based on the Community Reinforcement Approach

A promising option in substance abuse treatment is the Community Reinforcement Approach (CRA). The opioid antagonist naltrexone (NTX) may work in combination with nicotine replacement therapy (NRT) to block the effects of smoking stimuli in abstinent smokers. Effects of lower doses than 50 mg/dd. have not been reported. A study was conducted in Amsterdam in 2000/2001 with the objective to explore the effects of the combination NTX (25/50-mg dd.), NRT, and CRA in terms of craving and abstinence. In a randomized open label, 2 × 2 between subjects design, 25 recovered spontaneous pneumothorax (SP) participants received 8 weeks of treatment. Due to side effects, only 3 participants were compliant in the 50-mg NTX condition. Craving significantly declined between each measurement and there was a significant interaction between decline in craving and craving measured at baseline. The abstinence rate in the CRA group was nearly double that in the non-psychosocial therapy group (46% vs. 25%; NS) at 3 months follow-up after treatment.     

A randomized placebo-controlled trial of gabapentin for cocaine dependence

BACKGROUND: In laboratory animals, augmentation of GABA neurotransmission results in inhibition of cocaine self-administration and inhibition of reinstatement to cocaine-seeking behaviors. If parallel effects were observed in humans, GABA-ergic medication should be effective both in the abstinence-induction as well as in the relapse-prevention phase of cocaine dependence treatment. Gabapentin is an anticonvulsant medication that increases human brain GABA levels. We evaluated the safety and efficacy of gabapentin combined with relapse-prevention therapy in the treatment of cocaine-dependent individuals. DESIGN: The study involved 129 individuals with cocaine dependence. Of the 99 participants, who were randomized into a double-blind trial 88% were males, 66% were minorities and with an average age of 39 years (range 22-58 years). After 2 weeks of placebo lead-in, participants were randomized to receive either gabapentin 3200 mg (1600 mg bid) or placebo for 12 weeks, followed by 2 weeks of placebo lead-out. Prior to randomization, participants were stratified into four groups based on the principal route of cocaine use (smokers versus intranasal users) and the level of cocaine use during the 2 weeks of lead-in (high level versus low level). Throughout the 16 weeks study, participants received weekly individual relapse-prevention therapy. The outcome measures included: days of cocaine use and a binary indicator of abstinence based on urine toxicology test, self-reported cocaine craving and retention in treatment. RESULTS: Forty-nine percent of randomized patients completed 12 weeks of the trial. Retention did not differ by treatment group but cocaine-smokers dropped out of treatment at a significantly faster rate than intranasal users. For the entire sample, odds of cocaine use over the course of the study did not differ between gabapentin- and placebo-treated individuals. There was a significant difference in the odds of cocaine use between high and low-use groups, with the odds in high-use groups decreasing over time and odds in the low-use groups gradually increasing over the course of the study, such that by the end of the study low and high users were similarly likely to use cocaine. In the low-use group, there was a non-significant trend suggesting that gabapentin-treated subjects had more favorable outcome compared to placebo-treated individuals. There was no treatment effect on abstinence rates, craving or other substance use. Gabapentin at 3200 mg/day was very well tolerated in this group of cocaine-dependent participants. CONCLUSIONS: When combined with weekly individual relapse-prevention therapy, gabapentin 1600 mg bid was no more effective than placebo in the treatment of cocaine dependence. When reviewed in conjunction with other published studies, gabapentin and other GABA enhancing anticonvulsant medications may deserve further study as relapse-preventive agents in cocaine-dependent individuals who achieve abstinence early in treatment.     

Effect of flupenthixol on subjective and cardiovascular responses to intravenous cocaine in humans.

The effects of oral flupenthixol and intramuscular (i.m.) flupenthixol decanoate in combination with intravenous (i.v.) cocaine were evaluated in male cocaine abusers. Participants resided at an inpatient research unit for 27 days followed by an 11-day outpatient period. Oral flupenthixol (2.5 or 5.0 mg; p.o.) followed by flupenthixol decanoate (10 or 20 mg; i.m.) and placebo were investigated in individuals who were randomly assigned to one of three groups under double-blind conditions (placebo, low or high dose flupenthixol). During the inpatient period, participants had four fixed cocaine dosing sessions; each session they were administered four doses of i.v. cocaine (approx. 48 mg/70 kg), spaced 14 min apart. These sessions occurred once before medication (baseline phase), once following oral medication (oral phase), and twice following intramuscular medication (IM phase). Out of 23 participants, 18 completed the study; 4 of the 5 non-completers were in the high dose flupenthixol group. Overall, there were few subjective, cardiovascular, or cocaine pharmacokinetic differences between the placebo group and the low dose flupenthixol group, indicating that the low dose of flupenthixol was well tolerated, but ineffective. In the high dose flupenthixol group, two out of seven individuals (29%) experienced a dystonic reaction following oral flupenthixol and were medically discharged. Taken together, these findings indicate that flupenthixol is not a good candidate for treating cocaine abusers.     

Enhanced treatment outcomes for cocaine-using methadone patients.

Cocaine dependent methadone patients were randomly assigned to 6 months of high intensity cognitive-behavioral therapy or low intensity therapy. A repeated measures ANOVA was conducted with patients stratified on severity of cocaine use at baseline. Both treatment groups showed significant and equivalent reductions in cocaine use during the post-treatment period. Completing either therapy and lower cocaine severity at baseline were associated with lower proportion of cocaine-positive urines across a 48-week post-treatment period. Examination of the treatment x cocaine severity interaction provided some evidence that high-severity patients improved more if exposed to high intensity treatment than to low intensity treatment. Positive outcomes for therapy completers relative to non-completers increased over time. The results are consistent with several clinical trials showing that: (1) participation in treatment is associated with reductions in cocaine use; and (2) the relationship between treatment intensity and outcome is not linear and may better be explained by an interaction between patient and treatment factors.     

Cigarette smoking and short-term addiction treatment outcome

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.     

Bromocriptine treatment for cocaine addiction: association with plasma prolactin levels

Bromocriptine is a dopamine receptor agonist used with mixed success in the treatment of cocaine addiction. Variations in dopamine receptor sensitivity may help account for these differences. We evaluated this question in a 24-week outpatient controlled clinical trial in 70 cocaine-abusing (DSM-III) men (86% African-American, mean age 34 years, mean 39 months of regular cocaine use [predominantly smoked]). Subjects received 4 weeks of inpatient treatment. During the last 2 weeks they were inducted onto bromocriptine (maximum dose 2.5mg po tid) (n=35) or placebo (n=35). Plasma prolactin concentrations were assayed before and after the first bromocriptine dose (1.25mg po) as a measure of dopamine receptor sensitivity. After discharge, subjects continued on medication with weekly group counseling. Bromocriptine significantly suppressed prolactin concentrations (4.4 ng/ml decrease), while placebo did not (0.1 ng/ml decrease). Both groups decreased their cocaine use, with no significant group differences in retention in treatment or proportion of cocaine-positive urine samples. There was no significant association between basal plasma prolactin concentrations or prolactin response to first bromocriptine dose and either outcome measure. These data do not support the efficacy of bromocriptine treatment nor a role for prolactin concentration in predicting treatment response.     

A Combination of Isradipine and Naltrexone Blocks Cocaine’s Enhancement of a Cocaine Place Preference

Rats were conditioned by pairing cocaine with one side of an alley and placebo with the other. After conditioning, compared to Baseline and a placebo-control group, rats spent more time in the place of cocaine experience. Subsequently, there were further tests except now cocaine was given just before the test session in addition to one of two other kinds of injections. One of these additional injections was a placebo and the other was a combination of a small dose of isradipine (1 mg/kg) and a dose of naltrexone (3 mg/kg) (ISR+NTX). Measures of gross activity (movement from one side of the alley to the other) were taken during testing. ISR+NTX blocked cocaine’s ability to sustain a place preference. ISR+NTX also blocked sensitization of cocaine’s ability to enhance locomotor activity. This blockade of cocaine’s usual effects indicates that ISR+NTX may have a role in treating cocaine use disorders.     

Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder

Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence have been inconsistent. In this study, cocaine-dependent individuals with (n = 57) and without (n = 82) affective disorder were compared in a 12-week, double-blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug use were collected weekly. Affective symptoms were measured monthly. Subjects receiving CBZ attended more medication sessions (p = .03). The CBZ-treated affective group had a trend toward fewer cocaine-positive UDS (p = .08) and a significantly longer time to first cocaine use (p = .06). CBZ treatment did not have any impact on cocaine use in individuals without affective disorders.     

Adjunctive desipramine in the treatment of cocaine abusing schizophrenics.

Because schizophrenic patients have a lifetime prevalence rate for cocaine abuse between 15 and 50 percent, the use of adjunctive pharmacotherapy should be considered in cocaine-abuse treatment programs. This 12-week, open-label outpatient study compares 12 cocaine-abusing schizophrenic patients treated with desipramine (DMI) 100 to 150 mg and antipsychotic agents to 15 patients treated with only antipsychotic agents (no DMI). All 27 patients participated in a Dual Diagnosis Relapse Prevention (DDRP) program, which integrates traditional substance-abuse relapse prevention and psychiatric social skills training. The DMI group was more likely to complete the study (83% vs. 60%, odds ratio = 3.3, NS) and had fewer cocaine-positive urines during the last 6 weeks (20% vs. 50%, odds ratio = 4.0, p < .01). In the context of a specialized dual diagnosis treatment program, patients receiving DMI substantially decreased cocaine usage and had improved psychiatric symptoms.     

Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: a pilot study.

Cocaine abusers frequently report taking the drug in association with alcohol. This combined intake leads to the synthesis of cocaethylene, an active metabolite with effects similar to those of cocaine, but more prolonged. Since pharmacological effects of cocaethylene may partially account for the habit of cocaine abusers to take the drug in combination with ethanol, a main therapeutic goal in these patients should be making body fluids negative for cocaethylene. This randomized controlled open study conducted on 12 subjects co-abusers of cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in this study are restricted to the first 4 weeks of treatment when all the enrolled subjects were still available for examination. In fact, of the 12 subjects enrolled in the study only 4 (33%) completed the 12-week treatment. Of these, three were in the CBT group and one in the NTX/CBT group. Results show that CBT treated subjects remained in treatment longer than those assigned to either DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT-group urine tested positive almost always for both cocaine and cocaethylene. In contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically significant reduction, of positive urinalysis for both cocaine and cocaethylene, with respect to CBT alone. Moreover, across the first 4 weeks of treatment DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT alone. This pilot study suggests that the transient efficacy of pharmacological treatments in maintaining subjects drug free, does not add to the capability of CBT to retain them in treatment.     

Marriage and relationship closeness as predictors of cocaine and heroin use

Marriage has been cited as a protective factor against drug use, but the relationship between marriage and drug use has not been explored longitudinally during addiction treatment. The current study assessed individual trajectories of substance use during treatment as a function of marital status and perceived closeness of the marital relationship. A parallel-process growth model was used to (1) estimate the rate of change in percentage of cocaine-positive and heroin-positive urine samples, and (2) examine the relationship between marital status and drug use trajectories over 35 weeks, during and after treatment. Percent days of use for both drugs were lowest for married participants across all time points. Among married participants, reporting a close relationship with one's partner predicted less cocaine and heroin use. These findings suggest that being married and having a close relationship with one's spouse are associated with better outcomes over time. The causal nature of the association is suggested by previous research that has demonstrated the effectiveness of couples therapy as an adjunct to methadone maintenance.     

Participants receiving dehydroepiandrosterone during treatment for cocaine dependence show high rates of cocaine use in a placebo-controlled pilot study

Twenty-three cocaine-dependent participants were randomly assigned to receive either dehydroepiandrosterone (DHEA; n = 11; 100 mg/day) or placebo (n = 12) in the context of 12 weeks of thrice weekly cognitive-behavioral group counseling. Outcomes were retention, urine drug screening, cocaine craving, adverse experiences, and medication compliance. DHEA-treated participants averaged 45.8 (SD = 28.8) days in treatment, compared with 70.7 (SD = 20.6) days for placebo, r(21) = -2.4, p =.03, and provided 26.8% (SD = 29.3) of urine samples free of cocaine metabolite compared with 70.6% (SD = 39.9) for the placebo condition, r(21) = -3.0, p =.01. No differences were detected between conditions for cocaine craving or adverse experiences. High levels of medication compliance were documented. Results argue against using high doses of DHEA as a pharmacotherapy for cocaine dependence.     

Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials.

Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15-30 or 30-60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.     

High methadone dose significantly reduces cocaine use in methadone maintenance treatment (MMT) patients

AIM: To evaluate whether effective methadone treatment affects cocaine use. METHODS: 421 consecutive patients admitted to a methadone maintenance clinic in Israel (1993-2002) were prospectively studied. Patients' urine samples were analyzed for cocaine during months 1 and 13. RESULTS: On admission 55(13.1%) of 421 patients had urine positive for cocaine and 366 had negative. Of the 55 cocaine-positive patients, 45(81.8%) stayed in treatment at least one year, as did 267(73%) of cocaine-negative. After one year (n=312) 31 of 45 cocaine users stopped and 25 of 267 started. Methadone dose was highest in 31 patients who stopped cocaine (176.1+/-42.1 mg/ day), followed by 14 who did not stop (161.4+/-37.5 mg/day), and 25 who started during treatment (122.9+/-48.7 mg/day), or 242 who never used cocaine (119.5+/-48.4 mg/day) (ANOVA, F=15.6, p<0.0005). CONCLUSIONS: High methadone dose may reduce cocaine use in patients addicted to both heroin and cocaine.     

A double blind, placebo-controlled study of the effects of post-retrieval propranolol on reconsolidation of memory for craving and cue reactivity in cocaine dependent humans

Rationale/objectives

This study examined the effects of propranolol vs. placebo, administered immediately after a “retrieval” session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent “test” session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up.

Methods

CD participants received either 40 mg propranolol or placebo immediately following a “retrieval” CCE session. The next day, participants received a “test” session of CCE that was identical to the “retrieval” session except no medication was administered. Participants underwent a “follow-up” CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions.

Results

Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use.

Conclusions

This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted.     

Levodopa pharmacotherapy for cocaine dependence: choosing the optimal behavioral therapy platform

BACKGROUND: The dopamine precursor levodopa has shown some, albeit relatively weak, promise in treating cocaine dependence. This study sought to identify the most appropriate behavioral therapy platform for levodopa pharmacotherapy by evaluating its effect when administered in combination with behavioral platforms of varying intensities. METHOD: A total of 161 treatment-seeking cocaine dependent subjects received sustained release levodopa/carbidopa (400/100mg bid, Sinemet) or placebo delivered in combination with Clinical Management (ClinMan); ClinMan+cognitive behavioral therapy (CBT); or ClinMan+CBT+voucher-based reinforcement therapy (VBRT) in a 12-week randomized, placebo-controlled, double-blind (for medication condition) trial. Medication compliance was monitored with riboflavin (100mg/capsule) and the Medication Event Monitoring System. Protocol compliance was addressed in weekly, 10-min nurse-delivered ClinMan sessions. Weekly, 1-h CBT sessions focused on coping skills training. VBRT (with escalating reinforcer value) provided cash-valued vouchers contingent on cocaine-negative urine toxicology results. Urine benzoylecgonine assays collected thrice-weekly were analyzed by intention-to-treat criteria using generalized linear mixed models. RESULTS: Levodopa main effects were found on all outcome measures of cocaine use. Contrasts testing the levodopa-placebo difference within each behavioral platform found reliable effects, favoring levodopa, only in the VBRT platform. Levodopa treatment with vouchers produced higher proportions of cocaine-negative urines and longer periods of consecutive abstinence compared to other treatment combinations. CONCLUSION: This is the first study to find a significant treatment effect for levodopa and, in doing so, to demonstrate that the magnitude of this effect is dependent upon conditions of the behavioral therapy platform. The data support use of levodopa with abstinence-based reinforcement therapy as one efficacious combination in cocaine dependence disorder treatment.