N-Acetylcysteine for Youth Cannabis Use Disorder

Cannabis use is particularly prevalent and problematic among youth. Compared with only one in eleven cannabis-exposed adults, one in six cannabis-exposed youth develops cannabis use disorder. Moreover, youth are more prone than adults to potentially lasting adverse effects of cannabis use, including cognitive impairment, altered brain development, poor educational outcome, and diminished life achievement. Despite this, relatively little work has focused on developing optimally efficacious cannabis use disorder treatments, particularly among youth. Current evidence-based treatments convey generally small to modest effect sizes, and novel approaches are critically needed. Among the most promising approaches is the over-the-counter antioxidant medication N-acetylcysteine (NAC). Our team previously demonstrated superior NAC versus placebo (PBO) abstinence outcomes in youth with CUD who concurrently received the behavioral treatment contingency management (CM). Further work is now needed to test whether NAC is efficacious without a platform of CM. The proposed trial is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups. We will also serially assess cognitive task performance, examining changes in performance among participants who achieve abstinence versus those that do not. This proposed trial is the clear "next step" in the assessment of NAC as an extremely promising youth CUD treatment modality, and is positioned to inform researchers, clinicians, and the general public, addressing a critical need for optimization of youth CUD treatment.