A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents

Abstract

Objective: Preclinical findings suggest that the over-the-counter supplement N-acetylcysteine (NAC), via glutamate modulation in the nucleus accumbens, holds promise as a pharmacotherapy for substance dependence. The authors investigated NAC as a novel cannabis cessation treatment in adolescents, a vulnerable group for whom existing treatments have shown limited efficacy.

Method: In an 8-week double-blind randomized placebo-controlled trial, treatment-seeking cannabis-dependent adolescents (ages 15-21 years; N=116) received NAC (1200 mg) or placebo twice daily as well as a contingency management intervention and brief (<10 minutes) weekly cessation counseling. The primary efficacy measure was the odds of negative weekly urine cannabinoid test results during treatment among participants receiving NAC compared with those receiving placebo, in an intent-to-treat analysis. The primary tolerability measure was frequency of adverse events, compared by treatment group.

Results: Participants receiving NAC had more than twice the odds, compared with those receiving placebo, of having negative urine cannabinoid test results during treatment (odds ratio=2.4, 95% CI=1.1-5.2). Exploratory secondary abstinence outcomes favored NAC but were not statistically significant. NAC was well tolerated, with minimal adverse events.

Conclusions: This is the first randomized controlled trial of pharmacotherapy for cannabis dependence in any age group to yield a positive primary cessation outcome in an intent-to-treat analysis. Findings support NAC as a pharmacotherapy to complement psychosocial treatment for cannabis dependence in adolescents.

Figure 1

Proportion of negative urine cannabinoid tests (intent-to-treat analysis including all randomized participants, with urine cannabinoid tests assumed to be positive for all missed visits; n=116); adjusted for years of cannabis use, baseline urine cannabinoid test results, and major depressive disorder. OR=2.4 (95% CI: 1.1-5.2), χ²=4.72, p=0.029 NAC=N-Acetylcysteine, BL=Baseline Visit, FU=Post-Treatment Follow-Up Visit

Figure 2

Survivorship function for time to first negative urine cannabinoid test. Estimated survival function for N-acetylcysteine versus placebo participants; adjusted for years of cannabis use and baseline urine cannabinoid test results. NAC=N-Acetylcysteine

Figure 3

Retention: Proportion of randomized participants (n=116) attending visits. NAC=N-Acetylcysteine, BL=Baseline Visit, Rx=Medication Initiation, FU=Post-Treatment Follow-Up Visit