A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults

Kevin M. Gray, Susan C. Sonne, Erin A. McClure, Udi E. Ghitza, Abigail G. Matthews, Aimee L. McRae-Clark, Kathleen M. Carroll, Jennifer S. Potter, Katharina Wiest, Larissa J. Mooney, Albert Hasson, Sharon L. Walsh, Michelle R. Lofwall, Shanna Babalonis, Robert W. Lindblad, Steven Sparenborg, Aimee Wahle, Jacqueline S. King, Nathaniel L. Baker, Rachel L. TomkoLouise F. Haynes, Ryan G. Vandrey, Frances R. Levin

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


Background Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N = 302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n = 153) or placebo (n = 149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63–1.59, p = 0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

Original languageEnglish
Pages (from-to)249-257
Number of pages9
JournalDrug and Alcohol Dependence
StatePublished - Aug 1 2017

Bibliographical note

Funding Information:
This study was supported by National Institutes of Health [grant numbers UG1DA013727, UG1DA015831, UG1DA020024, UG1DA013714, UG1DA013732, U10DA013045, and HHSN271201200017C]. While the study was conducted within the National Drug Abuse Treatment Clinical Trials Network with facilitation by the National Institute on Drug Abuse Center for the Clinical Trials Network, funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The opinions in this paper are those of the authors and do not represent the official position of the U.S. government.

Publisher Copyright:
© 2017 Elsevier B.V.


  • Addiction
  • Cannabis
  • Cessation
  • Marijuana
  • N-acetylcysteine
  • Pharmacotherapy
  • Treatment

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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