Cocaine dependence is a chronically relapsing disorder for which its predominant behavioral therapies are associated with only partial efficacy. The goal of this study was to determine if the N-methyl-d-aspartate (NMDA) glutamate receptor partial agonist and cognitive enhancer, d-cycloserine (DCS), could boost the cocaine abstinence and treatment retention goals of cognitive behavioral therapy (CBT). This study employed a placebo-controlled, randomized double-blind trial design of 44 cocaine-dependent men enrolled in a 4-week outpatient Substance Abuse Treatment Program (SATP) at the Atlanta Veteran's Administration Medical Center. Subjects received 50mg of DCS or placebo prior to four weekly sessions of a condensed version of a manual-based CBT for cocaine dependence. Cocaine abstinence and treatment retention measures represented primary outcome variables. Relative to a 12-step based treatment-as-usual, an under-dosed CBT was associated with significant improvements in drug abstinence and treatment retention at 4-weeks and for maintenance of drug abstinence after four more weeks of follow-up. The robust response to the under-dosed CBT was not enhanced by the adjunct administration of DCS at either the 4- or 8-week endpoints. This controlled clinical trial failed to demonstrate an ability of DCS to boost the relapse prevention or treatment retention goals of CBT.

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