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

Am J Addict. Sep-Oct 2013;22(5):443-52. doi: 10.1111/j.1521-0391.2013.12034.x. Epub 2013 May 15.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / adverse effects
  • Acetylcysteine / therapeutic use*
  • Adult
  • Amino Acid Transport System y+ / drug effects*
  • Cocaine-Related Disorders / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Psychiatric Status Rating Scales
  • Psychological Tests
  • Secondary Prevention
  • Treatment Outcome


  • Amino Acid Transport System y+
  • SLC7A11 protein, human
  • Acetylcysteine