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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01675661.

Keywords: Addiction; Cannabis; Cessation; Marijuana; N-acetylcysteine; Pharmacotherapy; Treatment.

Conflict of interest statement

Conflict of Interest

Gray has received research support (medication only) from Pfizer. McRae-Clark has served as a consultant for Insys Pharmaceuticals and has received research support (medication only) from Pfizer. Walsh has received research support from Cerecor, Inc., and Braeburn Pharmaceuticals; has served as a consultant for AstraZeneca, Braeburn Pharmaceuticals, Camurus, Daiichi Sankyo, DURECT, Eli Lilly & Co., INSYS, Lightlake Therapeutics, KemPharm, Neurocrine, Novartis, Pfizer, Sun Pharma, and US WorldMeds; and has received speaker’s honoraria from PCM Scientific through unrestricted grants from Gilead, Indivior, and Merck. Lofwall has served as a consultant for Braeburn Pharmaceuticals, CVS Caremark, and PCM Scientific, and has received research support from Braeburn Pharmaceuticals. Vandrey has served as a consultant for Zynerba Pharmaceuticals, Battelle Memorial Institute, and CW Botanicals, and has served on an advisory panel for Insys Therapeutics. Levin has served as a consultant for GW Pharmaceuticals and Major League Baseball, and has received research support (medication only) from US WorldMeds. Sonne, McClure, Ghitza, Matthews, Carroll, Potter, Wiest, Mooney, Hasson, Babalonis, Lindblad, Sparenborg, Wahle, King, Tomko and Haynes report no competing interests.

Copyright © 2017 Elsevier B.V. All rights reserved.

Figures

Figure 1

CONSORT Diagram

Figure 2

Intent-to-treat urine cannabinoid test results BL=Baseline; NAC=N-acetylcysteine

Figure 3

Baseline tobacco use status and intent-to-treat urine cannabinoid test results BL=Baseline; NAC=N-acetylcysteine

Figure 4

Race and intent-to-treat urine cannabinoid test results BL=Baseline; NAC=N-acetylcysteine