The role of depressive symptoms in treatment of adolescent cannabis use disorder with N-Acetylcysteine

Relative to adults, adolescents are at greater risk of developing a cannabis use disorder (CUD) and risk may be exacerbated by co-occurring depressive symptoms. N-Acetylcysteine (NAC), an over-the-counter antioxidant, is thought to normalize glutamate transmission. Oxidative stress and glutamate transmission are disrupted in both depression and CUD. Thus, NAC may be particularly effective at promoting cannabis abstinence among adolescents with elevated depressive symptoms. Secondary analyses were conducted using a sub-sample of adolescents with CUD (N = 74) who participated in an 8-week randomized placebo-controlled clinical trial examining the efficacy of NAC for cannabis cessation. It was hypothesized that NAC would reduce severity of depressive symptoms, and that decreases depressive symptom severity would mediate decreases in positive weekly urine cannabinoid tests (11-nor-9-carboxy-Δ9-tetrahydrocannabinol). Additionally, it was expected that adolescents with greater severity of baseline depressive symptoms would be more likely to become abstinent when assigned NAC relative to placebo. Results from linear mixed models and generalized estimating equations did not suggest that NAC reduced severity of depressive symptoms, and the hypothesis that NAC's effect on cannabis cessation would be mediated by reduced depressive symptoms was not supported. However, an interaction between treatment condition and baseline severity of depressive symptoms as a predictor of weekly urine cannabinoid tests was significant, suggesting that NAC was more effective at promoting abstinence among adolescents with heightened baseline depressive symptoms. These secondary findings, though preliminary, suggest a need for further examination of the role of depressive symptoms in treatment of adolescent CUD with NAC.