A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.
Open accessAbstract
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 1200mg (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 1200mg 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.
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N-acetylcysteine's effect was not replicated in a larger clinical trial among adults, in which N-acetylcysteine and placebo groups did not differ in cannabis abstinence.
“However, its effect was not replicated in a larger clinical trial among adults, in which N-acetylcysteine and placebo groups did not differ in cannabis abstinence 70.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [70]
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Self-citation
- Authors
- Gray, K. M., Sonne, S. C., McClure, E. A., Ghitza, U. E., Matthews, A. G., McRae-Clark, A. L., Carroll, K. M., Potter, J. S., Wiest, K., Mooney, L. J., Hasson, A., Walsh, S. L., Lofwall, M. R., Babalonis, S., Lindblad, R. W., Sparenborg, S., Wahle, A., King, J. S., Baker, N. L., Tomko, R. L., Haynes, L. F., Vandrey, R. G., & Levin, F. R.
- Affiliations
- Medical University of South Carolina (US)
- National Institutes of Health (US)
- Emmes (United States) (US)
- Yale University (US)
- The University of Texas at San Antonio (US)
- University of California, Los Angeles (US)
- University of Kentucky (US)
- National Institute on Drug Abuse (US)
- Johns Hopkins University (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Gray, Kevin M.
- ORCID
- Venue
- Drug and Alcohol Dependence
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 177
- Pages
- 249-257
- ISSN
- 0376-8716 (ISSN-L)
- PMC
- PMC5535813
- OpenAlex
- W2624100118
- Cited by
- 157
- References
- 35
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 17 · 2023: 13 · 2022: 20 · 2021: 20 · 2020: 17 · 2019: 13 · 2018: 24 · 2017: 6
- FWCI
- 12.85
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Drug and Alcohol Dependence (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UKnowledge (University of Kentucky) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UG1DA013727, UG1DA015831, UG1DA020024, UG1DA013714, UG1DA013732, U10DA013045, HHSN271201200017C)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- cannabis use disorder, N-acetylcysteine, contingency management, medication adherence, cannabis abstinence, adolescents versus adults, treatment-seeking patients
- MeSH terms
- Acetylcysteine, Adolescent, Adult, Cannabis, Marijuana Abuse, Double-Blind Method, Female, Humans, Male, Marijuana Smoking, Sulpiride, Free Radical Scavengers, Treatment Outcome, Medication Adherence, Young Adult
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