A randomized, placebo-controlled laboratory study of the effects of D-cycloserine on craving in cocaine-dependent individuals

Abstract

Rationale: D-Cycloserine (DCS), a partial glutamate N-methyl-D-aspartate (NMDA) receptor agonist, enhances extinction of conditioned fear responding; preliminary data suggest that it may facilitate extinction of drug cue reactivity.

Objective: This study investigates DCS effects on cocaine cue craving and drug use in cocaine-dependent subjects.

Methods: Thirty-two subjects were randomly assigned to receive (1) DCS only, (2) DCS before sessions 1 and 3, placebo (PBO) before session 2, or (3) PBO only 15-min before each of 3 1-h cocaine cue exposure sessions conducted 1 day apart. Craving ratings were obtained before, during, and after sessions. Drug use and cue-induced craving were assessed 1 week after the last cue session.

Results: Repeated presentation of cocaine cues resulted in decreased craving both within and between sessions. DCS did not facilitate extinction learning and may have enhanced craving. The group that received three doses of DCS had significantly higher craving than the PBO group at the baseline ratings taken before sessions 2 and 3, as well as significantly higher cue-induced craving at follow-up. The group that received two doses of DCS did not differ from the PBO group. There were no group differences in postextinction cocaine use.

Conclusions: The reduction of cocaine cue reactivity in the PBO group suggests that the study procedures were sufficient to produce extinction. Under these conditions, DCS did not facilitate extinction and may have enhanced craving. Further studies of glutamatergic agents and extinction in cocaine dependence should include consideration of procedural variables that could have a major impact on study outcomes.

Figures

Fig 1

Craving rating across cue exposure sessions by group Means and standard errors for baseline, cue-elicited, and recovery craving rating by treatment group during all three extinction training sessions (M/W/F) as well as the 1-week follow-up cue exposure test. Baseline craving ratings are taken as the average of two craving ratings taken 20 and 5 minutes prior to initial cue onset. Cue-elicited craving was assessed immediately after each of three 10-min cue exposures (followed by 10-min rest periods), over one hour cue exposure sessions. Craving during the recovery period was assessed at 5, 30, and 60 minutes following the final rest period. Inset. Averaged cue-induced craving during each cue exposure session by treatment group.