Randomized Controlled Trial of D-Cycloserine in Cocaine Dependence: Effects on Contingency Management and Cue-Induced Cocaine Craving in a Naturalistic Setting

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.