Depressive symptoms and cannabis use in a placebo-controlled trial of N-acetylcysteine for adult cannabis use disorder.

Depression is common among individuals with cannabis use disorder (CUD), particularly those who present for CUD treatment. Treatments that consider this comorbidity are essential.

The goal of this secondary analysis was to examine whether N-acetylcysteine (NAC) reduced depressive symptoms among adults (age 8-50) with CUD (N=302) and whether the effect of NAC on cannabis cessation varied as a result of baseline levels of depression. Bidirectional associations between cannabis use amount and depression were also examined.

Data for the analysis were from a NIDA Clinical Trials Network multi-site clinical trial for CUD (CTN-0053). Adults with CUD (N=302) were randomized to receive 2400mg of NAC daily or matched placebo for 12 weeks. All participants received abstinence-based contingency management. Cannabis quantity was measured by self-report, and weekly urinary cannabinoid levels (11-nor-9-carboxy- 9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale.

Results found that depressive symptoms did not differ between the NAC and placebo groups during treatment. There was no significant interaction between treatment and baseline depression predicting cannabis abstinence during treatment. Higher baseline depression was associated with decreased abstinence throughout treatment and a significant gender interaction suggested that they may be particularly true for females. Cross-lagged panel models suggested that depressive symptoms preceded increased cannabis use amounts (in grams) during the subsequent month. The reverse pathway was not significant (i.e., greater cannabis use preceding depressive symptoms).

Conclusions: Results from this study indicate that symptoms of depression may be a barrier to cannabis cessation among adults, regardless of whether NAC is administered. Overall, the findings suggest that depressive symptoms should be considered clinically relevant within cannabis cessation programs for adults, and that more research is needed to explore treatments that could mitigate the impact of depressive symptoms on treatment outcomes. Treatments that address depressive symptoms concurrently with CUD treatment may be particularly beneficial.

Related protocols: CTN-0053