A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence

Abstract

Background: There remains no FDA approved medication for the treatment of cocaine dependence. Preclinical studies and early pilot clinical investigations have suggested that N-acetylcysteine (NAC) may be useful in the treatment of the disorder.

Objective: The present report assessed the efficacy of NAC in the treatment of cocaine dependence.

Methods: Cocaine-dependent volunteers (n = 111) were randomized to receive daily doses of 1,200 mg of NAC, 2,400 mg of NAC, or placebo. Participants were followed for 8 weeks (up to three visits weekly). At each of these visits, urine samples were collected, along with self-reports of cocaine use. Urine samples were assessed for quantitative levels of benzoylecognine (ie, cocaine metabolite).

Results: Overall, the primary results for the clinical trial were negative. However, when considering only subjects who entered the trial having already achieved abstinence, results favored the 2,400 mg NAC group relative to placebo, with the 2,400 mg group having longer times to relapse and lower craving ratings.

Conclusion: While the present trial failed to demonstrate that NAC reduces cocaine use in cocaine-dependent individuals actively using, there was some evidence it prevented return to cocaine use in individuals who had already achieved abstinence from cocaine.

Scientific significance: N-acetylcysteine may be useful as a relapse prevention agent in abstinent cocaine-dependent individuals.

Copyright © American Academy of Addiction Psychiatry.

Figures

Figure 1. Mean benzoylecognine levels and sub-sample size by group, baseline use, and treatment week

Panel A. BE levels # -- within Placebo group, levels from this week are lower relative to Week 0 * -- within NAC 1200 group, levels from this week are lower relative to Week 0 + -- within NAC 2400 group, levels from this week are lower relative to Week 0 Significant Group × Baseline Use × Time interaction, Wald χ2= 31.0, df = 16, p< .05. . No group differences are noted at any Treatment Week (n = 111). Error bars represent standard error of measurement. Panel B. Sample size (n) per group per week.

Figure 2. Results of exploratory analysis of time to relapse for subjects who were abstinent for at least 1 week prior to entering the medication trial

Note: Placebo n=8, 1200mg NAC n=4, 2400mg NAC n= 5

Figure 3. Exploratory analysis of overall mean craving ratings among initially abstinent individuals across the trial

Note: Due to excessive missing data points at Weeks 0 and 8, means included data from only Weeks 1 through 7. Error bars represent standard error of measurement. ** = BSCS level is significantly less than placebo, p < .001 ## = CSSA craving rating significantly less than NAC 1200mg and placebo, p < .01.