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Background: Contingency Management (CM) is being piloted as a treatment for stimulant use disorder in several US states, highlighting the need for treatment optimization. One important goal of optimization is decreasing drug use during the early stages of treatment, which has predicted success in other interventions. However, this "critical period" has not been reported in CM trials. The purpose of this analysis was to determine if, after accounting for baseline abstinence and incentive condition, abstinence in a CM trial for people with Cocaine Use Disorder (CUD) could be predicted by cocaine use during a first-week critical period., Methods: Eighty-seven participants with CUD were randomized to receive contingent high or low value incentives for cocaine abstinence or were in a non-contingent control group. Generalized estimating equations (GEE) were used to analyze urine test results over 36 timepoints during the 12-week intervention. To assess for a critical period, the first three visits were included in the GEE as a covariate for remaining urine test results., Results: Participants who provided more negative samples during the critical period were significantly more likely to produce a negative urine sample during the remainder of the trial, though some effects of group remained after controlling for the critical period., Conclusions: These results indicate that a critical period exists for CM trials, and it can explain a substantial amount of future performance. Early contact with an abstinence-contingent high magnitude alternative reinforcer may explain additional performance beyond the critical period, further justifying the use of high magnitude alternative reinforcers., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Abstinence is a widely-used endpoint in clinical trials of stimulant use disorders. A quantitative measure of frequency of use may be a more sensitive endpoint; however, it is important to establish that it is associated with post-treatment drug use. We examine and compare how within-treatment abstinence and frequency of use are related to two post-treatment longitudinal measures of drug use., Methods: For each of three existing stimulant use disorder clinical trial datasets, we examined the association between within-treatment frequency of use (based on urine screens), within-treatment abstinence, and post-treatment follow-up assessments of drug use (urine screens and reported days of use). In joint analyses that simultaneously model the effects of within-treatment abstinence and frequency of use, it is possible to discern their relative importance as predictors of post-treatment drug use during the 12 months following the end of treatment., Results: Results indicate a quantitative measure of within-treatment frequency of use was associated with longitudinal post-treatment follow-up assessments of drug use. Results from joint analyses of post-treatment follow-up drug use assessed by urine screens suggest that within-treatment frequency of use, rather than abstinence per se, is predictive of post-treatment drug use. However, results from joint analyses of self-report of days of use are equivocal., Conclusion: Results lend support to the use of a quantitative measure of within-treatment drug use as an alternative to complete abstinence. They suggest that some within-treatment use that fall short of complete abstinence may potentially represent clinically important improvements given their association with post-treatment drug use., Competing Interests: Declaration of Competing Interest Dr. Weiss has served as a consultant to Janssen Pharmaceuticals and GW Pharmaceuticals. All other authors report no potential conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The link between illicit drug use and impaired employee performance in the workplace has been assumed, but the relation has not been demonstrated clearly in research. This study was an evaluation of the relations between cocaine and opiate use, attendance, and performance in a job skills training program in a population with high rates of drug use., Methods: Out-of-treatment injection drug users (N = 42) attended a model therapeutic workplace where they could earn a maximum pay of around $10 per hour, 4 h every weekday, for 30 weeks. At the workplace, participants could complete practice trials on computer-based typing and keypad training programs. Participants were asked to provide urine samples thrice weekly, which were tested for opiates and cocaine., Results: Participants worked for more hours on a program that resulted in a flat hourly wage when their urine was negative for opiates and cocaine than when their urine was opiate and cocaine positive. Attendance was positively associated with opiate-negative samples during the study. When participants attended the workplace, however, their performance was not related to drug use. Participants completed the same number of practice trials, performed at the same accuracy, and typed at the same speed when they were positive and negative for cocaine and opiates., Conclusions: Contrary to common expectations, this study failed to show that the use of opiates or cocaine affected in-training performance, even though opiate and cocaine use predicted reduced attendance under some circumstances., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: 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., Case Summary: 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., Conclusion: 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Individuals who use cocaine have fewer cognitive resources needed to maintain abstinence. This is evidenced by blunted brain function during cognitive control tasks and reduced communication between brain regions associated with cognitive function. For instance, relapse vulnerability is heightened in individuals with less communication between the right and left frontoparietal executive control network (ECN). Given that recent cocaine use enhances such communication, it is plausible that recency of cocaine use influences interhemispheric ECN communication. However, it is unclear whether ECN communication weakens over the course of early cocaine abstinence, which may then enhance relapse risk., Methods: In ten men with cocaine use disorder, we conducted a preliminary assessment of the relationship between the number of days since last cocaine use (1-3days) and interhemispheric ECN coupling using resting state functional magnetic resonance imaging (fMRI)., Results: Reduced interhemispheric ECN coupling was associated with increasing days since last cocaine use; weaker coupling was also associated with lower urine cocaine metabolite concentrations. This association was more prominent in prefrontal than parietal ECN-subregions., Conclusions: Preliminary results indicate that resting state interhemispheric ECN coupling weakens within the first few days following last cocaine use. Because of the known link between reduced ECN interhemispheric coupling and relapse vulnerability, these results suggest that relapse risk may increase the longer an individual abstains during an early quit attempt. Treatments focused on reversing this coupling deficit may facilitate abstinence., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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., Competing Interests: This study was supported by an unrestricted, unsolicited investigator initiated request from Reckitt Benckiser Pharmaceuticals, Inc. (provided study drug only) who had no role in study design; collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. The authors alone are responsible for the content and writing of this manuscript. Drs. Gordon, Kinlock, and Fitzgerald received funding from Alkermes on a prior study. Dr. Schwartz did a one-time consultation for Reckitt-Benckiser on behalf of his employer (the Friends Research Institute). Dr. O’Grady has in the past received funding for his time from Reckitt-Benckiser. Dr. Vocci has consulted with and received other funding (meals, travel expenses) from the following companies: Braeburn Pharmaceuticals, Demerx, Indivior, Pinney Associates. He has received travel and meal expenses from Intratab Labs Inc., and received consulting fees from Alkermes and Usona Institute. All of Dr. Vocci’s consulting fees go to his employer, Friends Research Institute, Inc., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Modafinil is a medication approved for narcolepsy and shift work sleep disorder. It has both dopaminergic and glutamatergic activity that could be useful for the treatment of cocaine dependence. Modafinil has reduced cocaine subjective effects and cocaine self-administration in human laboratory trials and has reduced cocaine use in cocaine dependent patients in some clinical trials., Methods: This was an 8-week, double blind, placebo controlled clinical trial involving 94 cocaine dependent subjects. Subjects received 300mg of modafinil or identical placebo daily along with weekly individual therapy. The primary outcome measure was cocaine use measured by self-report, and confirmed by twice weekly urine benzoylecgonine tests (UBT). Additional outcome measures included cocaine craving measured by the Brief Substance Craving Scale and global improvement measured by the Clinical Global Impression Scale (CGI)., Results: The odds ratio (OR) in favor of abstinence for modafinil vs. placebo was 2.54 (p=. 03) and modafinil-treated subjects were significantly more likely than placebo-treated subjects to be abstinent from cocaine during the last 3 weeks of the trial, 23% vs. 9%, χ(2)=3.9, p<.05. Modafinil treated subjects were more likely to report very low levels of cocaine craving intensity and duration on the Brief Substance Craving Scale (OR=2.04, p=.03 and OR 1.06, p=.03 respectively). Modafinil-treated subjects were also more likely than placebo-treated subjects to rate themselves as "very much improved" on the CGI (OR=2.69, p=.03)., Conclusion: Modafinil may be an efficacious treatment for cocaine dependence., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Dual dependence on opiate and cocaine occurs in about 60% of patients admitted to methadone maintenance and negatively impacts prognosis (Kosten et al. 2003. Drug Alcohol Depend. 70, 315). Topiramate (TOP) is an antiepileptic drug that may have utility in the treatment of cocaine dependence because it enhances the GABAergic system, antagonizes the glutamatergic system, and has been identified by NIDA as one of only a few medications providing a "positive signal" warranting further clinical investigation. (Vocci and Ling, 2005. Pharmacol. Ther. 108, 94)., Method: In this double-blind controlled clinical trial, cocaine dependent methadone maintenance patients (N=171) were randomly assigned to one of four groups. Under a factorial design, participants received either TOP or placebo, and monetary voucher incentives that were either contingent (CM) or non-contingent (Non-CM) on drug abstinence. TOP participants were inducted onto TOP over 7 weeks, stabilized for 8 weeks at 300 mg daily then tapered over 3 weeks. Voucher incentives were supplied for 12 weeks, starting during the fourth week of TOP induction. Primary outcome measures were cocaine abstinence (Y/N) as measured by thrice weekly urinalysis and analyzed using Generalized Estimating Equations (GEE) and treatment retention. All analyses were intent to treat and included the 12-week evaluation phase of combined TOP/P treatment and voucher intervention period., Results: There was no significant difference in cocaine abstinence between the TOP vs. P conditions nor between the CM vs. Non-CM conditions. There was no significant TOP/CM interaction. Retention was not significantly different between the groups., Conclusion: Topiramate is not efficacious for increasing cocaine abstinence in methadone patients., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Background: Medications decreasing central noradrenergic activity have been associated with attenuation of cocaine effects., Aims: This pilot study examined the efficacy of doxazosin versus placebo for reducing cocaine use in treatment-seeking cocaine dependent persons., Methods: We screened 108 cocaine dependent subjects and assigned 35 participants to receive either doxazosin (8mg/day) or placebo for 13 weeks. Participants were titrated on the study medication according to two different schedules. During the initial phase of the study, patients were titrated onto the study medication over an 8-week period (DOX-slow). After reviewing data from our human laboratory study, a second phase was initiated, wherein titration was accelerated to a 4-week period (DOX-fast). All participants received weekly cognitive behavioral therapy. Urine toxicology was performed thrice weekly., Results: Baseline subject characteristics were comparable. Thirty subjects entered the study: 8 subjects in DOX-slow, 9 subjects in DOX-fast, and 13 subjects in placebo. Total number of cocaine-negative urines was significantly increased in the DOX-fast group; and percentage of total cocaine-negative urines by group were 10% for DOX-slow group, 35% for DOX-fast group, and 14% for placebo (χ(2)=36.3, df=2, p<0.0001). The percentage of participants achieving two or more consecutive weeks of abstinence by group was 0% for DOX-slow group, 44% for DOX-fast group, and 7% for placebo (χ(2)=7.35, df=2, p<0.023)., Conclusions: This pilot study suggests the potential efficacy of doxazosin when rapidly titrated in reducing cocaine use., (Published by Elsevier Ireland Ltd.)

Background: Methadone maintenance for heroin dependence reduces illicit drug use, crime, HIV risk, and death. Typical dosages have increased over the past few years, based on strong experimental and clinical evidence that dosages under 60 mg/day are inadequate and that dosages closer to 100mg/day produce better outcomes. However, there is little experimental evidence for the benefits of exceeding 100 mg/day, or for individualizing methadone dosages. We sought to provide such evidence., Methods: We combined individualized methadone dosages over 100 mg/day with voucher-based cocaine-targeted contingency management (CM) in 58 heroin- and cocaine-dependent outpatients. Participants were randomly assigned to receive a fixed dose increase from 70 mg/day to 100mg/day, or to be eligible for further dose increases (up to 190 mg/day, based on withdrawal symptoms, craving, and continued heroin use). All dosing was double-blind. The main outcome measure was simultaneous abstinence from heroin and cocaine., Results: We stopped the study early due to slow accrual. Cocaine-targeted CM worked as expected to reduce cocaine use. Polydrug use (effect-size h=.30) and heroin craving (effect-size d=.87) were significantly greater in the flexible/high-dose condition than in the fixed-dose condition, with no trend toward lower heroin use in the flexible/high-dose participants., Conclusions: Under double-blind conditions, dosages of methadone over 100mg/day, even when prescribed based on specific signs and symptoms, were not better than 100mg/day. This counterintuitive finding requires replication, but supports the need for additional controlled studies of high-dose methadone., (Published by Elsevier Ireland Ltd.)

Unlabelled: This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants., Design: One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites., Methods: Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained., Results: Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04)., Conclusions: Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The purpose of this double-blind, randomized, outpatient study was to evaluate the reinforcing and subjective effects of modafinil (200, 400, or 600 mg) in cocaine abusers. Twelve participants (2 female, 10 male) completed this study, consisting of 3 blocks of 7 sessions; each block tested a difference dose of modafinil. During the first 2 sessions of each block, participants "sampled" 1 of the doses of modafinil, and placebo. These doses of modafinil and placebo were available for the subsequent five choice sessions of the block. In each choice session, participants had an opportunity to administer active or placebo capsules. Modafinil administration did not differ from placebo administration, and subjective-effects ratings were not systematically altered as a function of modafinil dose. Results suggest that modafinil does not have abuse liability in cocaine abusers., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Cocaine dependence is a major public health problem for which there is no FDA-approved pharmacological treatment. Baclofen is a GABA(B) receptor agonist that in preclinical and early pilot clinical trials has shown promise for the treatment of cocaine dependence. The purpose of this multi-site, double-blind study, was to compare the safety and efficacy of baclofen (60 mg/day) vs placebo in an 8-week treatment of individuals with severe cocaine dependence. The primary outcome measure was subjects' self-reported cocaine use substantiated by urine benzoylecgonine (BE). Analysis of the data did not show a significant difference between the groups treated with baclofen and placebo. The current results do not support a role for 60 mg baclofen in treating cocaine dependence in the population studied. The contrast of this result to earlier, preclinical and human pilot data with baclofen may reflect the trial's focus on severe cocaine-dependent users, and/or the need for a higher baclofen dose. Baclofen's potential as a relapse prevention agent was not tested by the current design, but may be a useful target for future studies.

To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 x 3 (dosexcontingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100mg/day, double-blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or "split"). The "split" contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was "split" between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The split 100mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required.

Background: There is currently no FDA-approved medication for cocaine dependence and no standard primary outcome measure for reduction of cocaine use in cocaine-dependence trials. The ability to detect a significant medication effect will depend, in part, on the primary outcome measure utilized. The goal of the present paper is to compare self-report or either of two urine toxicology measures used alone to a relatively new measure -- the SRPHK1 -- which combines self-report, quantitative urine benzoylecgonine levels, and an estimate of the concordance between the two to determine the cocaine-use status of each study day., Method: Datasets from two separate randomized, placebo-controlled cocaine-dependence trials were used to compare four cocaine-use outcome measures., Results: The two data sets yielded very similar findings and suggest that the combined measure is associated with significantly fewer missing data than urine toxicology and that estimated cocaine use varied significantly depending on which measure was used, with the lowest use estimate being yielded by self-report, the highest by the two urine toxicology measures evaluated, and an intermediate value obtained using the combined measure. The results also suggest that the concordance between self-report and urine toxicology is around 90% at the beginning of the clinical trial but decreases to around 75% by the end of the trial., Conclusion: By combining the objectivity of urine toxicology with the reduced incidence of missing data characteristic of self-report, the SRPHK1 may provide advantages over self-report or urine toxicology measures used alone. In any case, the SRPHK1 provides an interesting complement to these other outcome measures and may warrant further evaluation.

Although improvement in psychosocial functioning is a common goal in substance-abuse treatment, the primary outcome measure in most cocaine trials is urinalysis-verified cocaine use. However, the relationship between cocaine use and psychosocial outcomes is not well documented. To investigate this relationship and identify the optimal urine-screen method, we retrospectively analyzed data from two 25-week randomized controlled trials of abstinence reinforcement (AR) in 368 cocaine/heroin users maintained on methadone. Cocaine use was measured thrice weekly by qualitative urinalysis, benzoylecgonine concentration (BE), and an estimate of New Uses of cocaine by application of an algorithm to BE. Social adjustment (SAS-SR), current diagnosis of cocaine dependence (DSM-IV criteria), and depression symptoms (Beck Depression Inventory) were determined at study exit. Cocaine use was significantly lower in AR groups than in controls. Across groups, in-treatment cocaine use was significantly associated with worse social adjustment, current cocaine dependence, and depression at exit. Significant differences were detected more frequently with New Uses than qualitative urinalysis or BE. Nevertheless, the amount of variance accounted for by the urine screens was typically <15%. Cocaine use during treatment, especially when measured with New Uses criteria, can predict psychosocial functioning, but cannot substitute for direct measures of psychosocial functioning.

Background: GABAergic medications appear to reduce the reinforcing effects of cocaine by attenuating cocaine-induced dopamine release. This study evaluated gabapentin and tiagabine compared to placebo in reducing cocaine taking behavior., Methods: A total of 76 treatment seeking, cocaine dependent, methadone-treated, predominately Caucasian male subjects were randomly assigned to tiagabine 24 mg/day (N=25), gabapentin 2400 mg/day (N=26) or placebo (N=25) in a 10-week double-blind placebo-controlled trial. Study medications were slowly increased to their full dosages by the end of week 5 and maintained through week 10. The primary outcome measure was thrice-weekly drug free urine samples., Results: Treatment retention was significantly less for the gabapentin group relative to the other groups (log rank=5.29, d.f.=1, p=0.02). The proportion of cocaine-free urine samples during weeks 6-10 was significantly larger in the tiagabine treated group (p<0.05). The longitudinal data showed significant change in thrice-weekly cocaine free urines that reached a greater abstinent rate for the tiagabine treated group (22%) compared to gabapentin (5%) or placebo (13%) treated groups. Mixed-effects ordinal regression models showed a significant tiagabine by time interaction compared to gabapentin (Z=2.48, d.f.=1, p=0.01) and placebo (Z=3.90, d.f.=1, p=0.0001). The gabapentin group did not differ from placebo., Conclusion: Gabapentin showed poor treatment retention and ineffectiveness in reducing cocaine use. Tiagabine significantly reduced cocaine taking behavior compared to placebo or gabapentin among methadone-stabilized cocaine abusers.

Background: Cocaine dependence is a major public health problem for which there is no FDA-approved pharmacological treatment. Selegiline is an irreversible selective inhibitor of monoamine oxidase type B (MAO-B) which may affect cocaine addiction through several potential mechanisms. In this study, selegiline transdermal system (STS) was compared to placebo as a treatment for cocaine dependence. This multi-site, double-blind trial of 300 subjects with cocaine dependence assessed the efficacy of selegiline using subject self-reported cocaine use substantiated by urine benzoylecgonine (BE) as the primary outcome measure. Analysis of the data did not show a significant effect for selegiline over placebo. This study does not support a role for selegiline in treating cocaine dependence. The contrast of this result to earlier, promising preclinical and human pilot data could be due to factors associated with sample size, patient characteristics, dose, or poor predictive validity of preclinical models.

The purpose of this double-blind, outpatient study was to evaluate the reinforcing and subjective effects of the uncompetitive N-methyl-d-aspartate (NMDA) antagonist memantine in cocaine-dependent humans. Eight participants (two females, six males) completed this study which consisted of three blocks of seven sessions; each block tested a different dose of memantine. During the first two sessions of each block, participants "sampled" the memantine capsule (10, 20, or 30 mg) and the placebo capsule that were available for the next five sessions. During the five subsequent sessions, participants had an opportunity to self-administer either the active or placebo capsule. Memantine was not reinforcing and subjective-effects ratings were not altered as a function of dose. Results suggest that these doses of memantine do not have abuse liability in cocaine-dependent individuals.

Background: Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence., Methods: The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT)., Results: Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi2 = 3.9, d.f. = 1, P = 0.05)., Conclusion: Topiramate may be effective for the treatment of cocaine dependence.

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.

Background: Multiple lines of evidence suggest both dopaminergic and serotonergic involvement in the reinforcing effects of cocaine. Medications such as olanzapine, which block dopamine D2 receptors, as well as serotonin receptors 5HT2A and 5HT2C may be able to reduce cocaine use in cocaine dependent patients by reducing the euphoric effects of cocaine and attenuating cocaine craving., Methods: This was a 12-week, double blind, placebo controlled, pilot trial involving 30 cocaine dependent subjects. Subjects received either olanzapine (10 mg/day) or identical placebo. Outcome measures included treatment retention, qualitative urine benzoylecgonine tests, cocaine craving, clinical global impression scores, and results from the addiction severity index., Results: Treatment retention was slightly, but significantly, better in the placebo-treated subjects. Placebo-treated subjects were more likely to be abstinent from cocaine during the trial compared to olanzapine-treated subjects, based on urine benzoylecgonine results. Olanzapine was not superior to placebo in any outcome measure., Conclusions: The results of this trial do not support the usefulness of olanzapine for the treatment of cocaine dependence. In fact, olanzapine may worsen cocaine treatment outcome.

The quest for predictive utility of baseline demographic and drug use characteristics has been difficult. The present article draws data from two studies of cocaine-dependent individuals (N = 297) in treatment at clinics in Los Angeles, and examines the utility of socio-demographic characteristics of patients and in-treatment performance variables as predictors of success at treatment end, 6 and 12 month follow-up assessments. Socio-demographic variables examined are age, gender, ethnicity, and educational attainment; drug use variables include years of cocaine use, self-reported days of cocaine use, the Addiction Severity Index drug composite score, and two composite measures cited in the literature. The in-treatment variables examined include cocaine urine toxicology results, number of weeks retained, and measures of compliance. The self-reported number of days of cocaine use in the past 30 days provides the most predictive utility of all baseline variables evaluated, and is the most parsimonious of the significant variables associated with substance use at all subsequent timepoints. Matching cocaine-dependent patients with treatment types or intensities based on the self-reported number of cocaine use days at intake may increase patient success rates.

This screening trial evaluated whether amantadine hydrochloride (100 mg bid) demonstrated sufficient clinical efficacy compared to placebo to recommend development as a pharmacotherapy for cocaine dependence. Participants were randomized to amantadine (n=34) or placebo (n=35) conditions in a 16-week, placebo-controlled, double blind trial with three times per week group counseling. Amantadine-treated participants were retained significantly longer than placebo. Based on results of a joint probability index for urine drug testing results (i.e. the proportion of cocaine-metabolite free urine samples divided by the number of participants assigned to the condition), participants assigned to amantadine were found to be significantly more likely to be cocaine abstinent on the last day of 8-weeks of treatment than participants assigned to placebo. Results at the end of 16 weeks of treatment were similar. Standard measures of urine drug testing consistently favored the amantadine condition over placebo, although not at levels of statistical significance. There was no statistical significance infrequency or severity of reported adverse events by treatment condition. Participants assigned to amantadine exhibited greater reductions in global staff ratings of cocaine dependence severity from baseline to termination compared with placebo. There were no significant differences in frequency or severity of reported adverse events by treatment condition. These results provide moderate support for further study of amantadine for the treatment of cocaine dependence.

Stress plays an important role in substance abuse problems. For example, in studies with rodents stress induces reinstatement of opioid and cocaine self-administration. In addition, attenuation of the stress response by pharmacological adrenalectomy using ketoconazole, a cortisol synthesis inhibitor, reduces cocaine self-administration in rodents. In contrast, studies in primates and humans have produced conflicting results using cortisol synthesis inhibitors for attenuating cocaine-related behaviors and subjective effects. To explore the treatment implications of these findings, ketoconazole's (600-900 mg daily) ability to reduce heroin and cocaine use was compared with placebo in 39 methadone maintained patients with a history of cocaine abuse or dependence during a 12-week double blind trial. Contrary to the predicted effects, both heroin and cocaine use increased after patients were stabilized on methadone and ketoconazole. Depressive and withdrawal symptoms improved no more with ketoconazole than with placebo treatment, and side effects were greater on ketoconazole than placebo. As reported before with methadone treatment, morning cortisol levels were significantly lower than normal values throughout the clinical trial, but were not lower with ketoconazole than placebo treatment. Thus, in agreement with the negative results from acute dosing studies in primates and humans, chronic ketoconazole treatment does not appear to reduce cocaine or opioid use in humans maintained on methadone.

We examined the effects of urine testing frequency on treatment outcome in a contingent methadone take-home program. Study patients who submitted<80% opiate and/or cocaine positive urines during a 5-week baseline received 60 mg methadone throughout the study, submitted urine samples on Monday, Wednesday, and Friday, and were randomized into one of three take-home incentive conditions. Study patients could receive three take-home doses per week if one urine sample randomly selected each week (Weekly; n=16) or each month (Monthly; n=18) was negative for opiates and cocaine. Take-homes for Random Drawing control patients (n=19) were determined weekly independent of urine test results. Subjects in the Weekly group showed an immediate increase from baseline in percentage of drug-free urines; those in the Monthly group showed a gradual increase over the first 3 months; and those in Random Drawings showed a decline in percentage of drug-free urines over time. The percentage of patients with sustained (8 or more weeks) opiate and cocaine abstinence was 56.6, 38.9 and 10.5% for Weekly, Monthly and Random Drawing groups, respectively (P<0.002). These results confirm that methadone take-homes contingent on drug-free urines prevent a decline in treatment performance over time and suggest that abstinence can be sustained with urine testing conducted as infrequently as once a month.

Although a number of cocaine use variables are available for use in treatment outcome studies, there is little information on how strongly these variables are related or their relative sensitivity for detecting treatment group differences. Eight continuous and categorical variables of cocaine use obtained at 6-, 12-, 18-, and 24-month follow-ups, four event history variables, and one summary measure of cocaine use over the 24-month follow-up period were examined. The variables were generally correlated 0.30--0.50 or greater. An exploratory factor analysis in which the repeated measures were averaged across follow-up points yielded two factors, one made up of incidence of use variables (e.g. percent days cocaine use, monetary value of cocaine, abstinence status, time to relapse, urine toxicology) and a second consisting of perceived severity of use variables (e.g. drug and cocaine composites, craving). This factor solution was supported by confirmatory factor analyses conducted at each follow-up point. None of the variables yielded significant differences between the two treatment conditions in the study, standard group and individualized relapse prevention continuing care. However, monetary value of cocaine used and urine toxicology variables yielded the largest effect sizes (eta(2)=0.020 and 0.010, respectively).

Sixty-one cocaine dependent outpatients submitted a single urine sample at least 1 week prior to entry into a 4-week treatment study. Participants were then expected to provide three urine samples per week during the month of treatment. The 61 patients studied here all completed treatment and provided an average of more than 11 of 12 scheduled urine samples. Participants who submitted a cocaine-positive sample prior to treatment provided more positive urine samples during the 4-week trial, were less likely to be completely abstinent during the month, and took longer to reach an initial abstinence criterion of three consecutive cocaine-free urines. Thus, a single pretreatment urine test represents a powerful predictor of subsequent cocaine use. The results suggest that future randomized trials stratify group assignment based on the results of a baseline urine test.

Influence of parental alcohol/substance abuse on methadone maintenance therapy (MMT) outcome was examined in 164 DSM-III-R opioid dependent adults with no other current DSM Axis I disorder. Family history positive patients had more DSM-III-R opioid dependence symptoms and were more likely to be classified as severely dependent. However, when placed on identical daily doses of methadone (50 mg), they had lower rates of illicit opioid use but higher rates of cocaine use than family history negative patients. Both effects remained significant after adjusting for gender and race. These results suggest that common genetic factors may underlie both susceptibility to heroin dependence and response to therapeutic methadone treatment.

This study examined the effectiveness of short-term contingency management for eliminating cocaine use and increasing full day treatment attendance with pregnant methadone-maintained women randomly assigned to either an escalating voucher incentive schedule (n=44) or non-incentive (n=36) conditions. Full day treatment attendance and urine toxicology for cocaine and heroin were assessed and consequated for 14 days. The escalating voucher incentive schedule significantly increased full day treatment attendance and drug abstinence compared to the non-incentive schedule. These results suggest that reinforcing the co-occurrence of two required behaviors (treatment attendance and abstinence from illicit drug use) is effective, and may be an important adjunct to methadone pharmacotherapy for treating pregnant drug dependent women.

Structured treatments for cocaine dependence have been shown to be effective despite high attrition rates. What is unclear is what level of treatment intensity is needed to improve and sustain patient outcomes, especially among low SES urban residents. This study evaluated whether there were differences between two levels of treatment intensities for cocaine dependence in reducing substance use and improving health and social indicators. Ninety-four cocaine dependent predominantly African-American male veterans were randomly assigned to either a 12 h/week day hospital program (DH12) or a 6 h/week outpatient program (OP6) and were evaluated at baseline, during treatment and at 4 and 7 months post-treatment. Both treatments stressed abstinence, behavior change and prosocial adjustment and only differed in level of treatment intensity. During treatment measures included urine toxicologies, program attendance, treatment completion and aftercare attendance. Participants reported a 52% reduction in days of cocaine use and experienced significant improvements in employment and psychiatric functioning at seven months post-treatment. However, there was no significant difference between the DH12 and OP6 programs in terms of abstinence during treatment, treatment completion, treatment or aftercare attendance or any Addiction Severity Index (ASI)-related variable assessing level of functioning at 4 and 7 months. While future research with a larger community-based sample that includes female clients is necessary, the current findings demonstrate that a 6 h/week program is just as effective and thus has a significant cost savings compared to a 12 h/week treatment modality for cocaine dependence.

Results of preclinical studies suggest that pergolide, a mixed D(1)/D(2) dopamine receptor agonist, may be useful in treating cocaine dependence. To empirically investigate this possibility, we conducted a 5-year, double-blind, placebo-controlled clinical trial of two doses of pergolide (0.05 and 0.25 mg bid) in subjects with cocaine dependence and combined cocaine/alcohol dependence. Data analysis was performed on an intent to treat population (N=358) and a per protocol population (N=108) with urine drug screens (UDS) used as the main outcome measure. There were no significant effects on UDS at either pergolide dose. Pergolide had no significant effect on alcohol use in the comorbid alcohol/cocaine dependence group. Pergolide does not appear to have clinical value in the treatment of cocaine dependence or in decreasing alcohol use in cocaine-dependent individuals at the presently studied doses.

This study measured effectiveness of behavioral day treatment plus abstinence contingent housing and work therapy (DT+) versus behavioral day treatment alone (DT). A randomized controlled trial assessed participants at baseline, 2 and 6 months. Participants (N=110) met criteria for cocaine abuse or dependence, non-psychotic mental disorders, and homelessness. DT+ achieved greater abstinence at 2 and 6 months and more days housed at 6 months than DT. Effectiveness of DT+ was demonstrated, with greatest impacts on abstinence outcomes. Results replicated earlier work demonstrating effectiveness of behavioral day treatment and contingency management as an effective combination for cocaine abusing homeless persons.

A broad range of baseline subject variables was evaluated to identify predictors of 7-month cocaine use for 160 lower socioeconomic cocaine dependent male veteran patients participating in either an intensive 1-month day hospital (DH; n=90) or a 1-month inpatient (INP; n=70) treatment program. The baseline measures included sociodemographic variables, the seven Addiction Severity Index composite scores, cocaine urine toxicology, craving, the SCL-90 total score, and lifetime psychiatric diagnoses. Since a proportion of subjects who reported no use at follow-up had positive urines, both liberal and conservative data estimation strategies were employed for subjects without urine toxicology data at follow-up who had reported no use (21% of subjects). Analyses were done separately for the DH and INP subjects. Under the conservative definition of cocaine abstinence/use, univariate correlations of predictor variables with 7-month cocaine use revealed no statistically significant relationships. Under the liberal definition of cocaine abstinence/use, only one variable, greater severity of alcohol problems at intake predicted cocaine abstinence at outcome. Because of the inability to predict treatment success, originally planned logistic regression analyses were not undertaken. The findings point to the difficulty of predicting long-term outcomes in cocaine dependent patients based on baseline information and to the importance of obtaining objective data on cocaine use.

The primary goal of this study was to identify factors associated with patients leaving a 3-day hospital detoxification unit against medical advice (AMA). Medical records of 302 patients who were admitted for alcohol or other drug withdrawal were reviewed. Variables examined were: demographics, reported history of drug use, urine toxicology at admission, medication received during the detoxification, and admission day. Data were analyzed using a case-control design. Logistic regression was used to identify independent predictors. We found that being younger, having a shorter history of cocaine abuse, being admitted on a Friday and being an opiate dependent patient treated with clonidine only during the detoxification, were significantly associated with leaving AMA. These findings may provide information that can help clinicians identify those patients who are most at risk for leaving AMA. This will in turn allow them the opportunity to initiate preventive measures to decrease unnecessary attrition and improve utilisation of treatment resources.

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.

Assessments of the possible consequences of prenatal exposure to cocaine have been limited by lack of control for socio-demographic confounders and lack of follow-up into the school years. We evaluated intelligence at ages 6-9 years in 88 children from a cohort of 280 born between September 1, 1985 and August 31, 1986 and identified at birth as cocaine-exposed, and in a group of unexposed (n = 96) births of comparable gender and birthweight. IQ scores did not differ between children with and without prenatal exposure to cocaine (mean 82.9 vs. 82.4, difference = 0.5 points, 95% CI-3.1, 4.1); results were unchanged with adjustment for child height, head circumference and prior residence in a shelter or on the street, and for caregiver IQ and home environment (mean difference = 2.2 points, 95% CI-1.5, 5.8).

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