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Randomized controlled trial of d-cycloserine in cocaine dependence: Effects on contingency management and cue-induced cocaine craving in a naturalistic setting.

ABSTRACT: Cocaine dependence constitutes a significant public health concern. This randomized, double-blind, placebo-controlled trial tested a novel approach to reducing cocaine use among cocaine-dependent individuals with d-cycloserine, a drug known to enhance learning and some learning-based therapies. Urine samples and cocaine craving were assessed across three phases: induction (Weeks 1-2), treatment (Weeks 3-5; urinalysis-based contingency management plus exposure therapy), and posttreatment (Weeks 6-7). During the treatment phase, either 50 mg of d-cycloserine or placebo was administered after delivery of urinalysis feedback with potential monetary reward and before exposure therapy sessions in naturalistic contexts individually associated with cocaine use. d-cycloserine significantly improved learning on an operant laboratory task. Contingency management significantly reduced cocaine use and craving. d-cycloserine did not significantly affect cocaine use or craving in the treatment phase. Craving significantly increased for the d-cycloserine group during the post treatment phase. Therefore, although the study showed that d-cycloserine was capable of improving learning, enhancement of learning-based therapy was not observed. Moreover, no differences in behavioral measures of cocaine demand (cocaine purchasing task) or monetary or sexual delay discounting were observed across phases or between groups in any phase. These results are somewhat consistent with previous findings suggesting that d-cycloserine administration increases cocaine craving, although they differ from other findings showing that d-cycloserine administration reduces alcohol or nicotine cravings. Methodological variables (e.g., guided vs. unguided exposure therapy sessions, length of extinction exposure) likely play a role in dissimilar findings observed across studies. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

SUBMITTER: Johnson MW

PROVIDER: S-EPMC6994347 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The relative impact of chronic vs acute cocaine on dependence-related variability in reward processing in cocaine-dependent individuals (CD) is not well understood, despite the relevance of such effects to long-term outcomes. To dissociate these effects, CD (N=15) and healthy controls (HC; N=15) underwent MRI two times while performing a monetary incentive delay task. Both scans were identical across subjects/groups, except that, in a single-blind, counterbalanced design, CD received intravenous cocaine (30 mg/70 kg) before one session (CD+cocaine) and saline in another (CD+saline). Imaging analyses focused on activity related to anticipatory valence (gain/loss), anticipatory magnitude (small/medium/large), and reinforcing outcomes (successful/unsuccessful). Drug condition (cocaine vs saline) and group (HC vs CD+cocaine or CD+saline) did not influence valence-related activity. However, compared with HC, magnitude-related activity for gains was reduced in CD in the left cingulate gyrus post-cocaine and in the left putamen in the abstinence/saline condition. In contrast, magnitude-dependent activity for losses increased in CD vs HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-saline. Across outcomes (ie, successful and unsuccessful) activity in the right habenula decreased in CD in the abstinence/saline condition vs acute cocaine and HC. Cocaine-dependent variability in outcome- and loss-magnitude activity correlated negatively with ratings of cocaine craving and positively with how high subjects felt during the scanning session. Collectively, these data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-related insensitivity to reinforcing outcomes/'liking', but having no discernible effect on dependence-related alterations in incentive salience/'wanting'. The relationship of drug-related affective sequelae to non-drug reward processing suggests that CD experience a general alteration of reward function and may be motivated to continue using cocaine for reasons beyond desired drug-related effects. This may have implications for individual differences in treatment efficacy for approaches that rely on reinforcement strategies (eg, contingency management) and for the long-term success of treatment.

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Randomized controlled trial of d-cycloserine in cocaine dependence: Effects on contingency management and cue-induced cocaine craving in a naturalistic setting.

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