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

Abstract

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

Objectives: The goal of this secondary analysis was to examine whether N-acetylcysteine (NAC) reduced depressive symptoms among adults (age 18-50) 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.

Methods: Data for this secondary analysis were from a National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) multi-site clinical trial for CUD. Adults with CUD (N = 302) were randomized to receive 2400 mg 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-Δ9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale.

Results: 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 this 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 suggest that depression may be a risk factor for poor CUD treatment outcome and therefore should be addressed in the context of treatment. However, results do not support the use of NAC to concurrently treat co-occurring depressive symptoms and CUD in adults.

Trial registration: Clinicaltrials.gov: NCT01675661.

Keywords: Cannabis; Cannabis use disorder; Depression; Marijuana; Mood; N-acetylcysteine; Structural equation modeling.

Conflict of interest statement

Rachel L. Tomko, Nathaniel L. Baker, Caitlyn O. Hood, Amanda K. Gilmore, Erin A. McClure, Lindsay M. Squeglia, Aimee L. McRae-Clark, and Susan C. Sonne declare that they have no conflict of interest. Kevin M. Gray has provided consultation to Pfizer, Inc.

Figures

Figure 1.

Structural equation model used to assess the cross-lagged relationship between depression scores (Xt) and cannabis use in grams (Yt) at study baseline (0), and 4 study treatment and follow-up weeks (4, 8, 12, FU). Note. The model illustrates the autocorrelated relationships (β) between longitudinal outcome measures (HAD-D depression scores and cannabis use quantity in grams), cross-lagged relationships (γ) between the two outcome measures and synchronous relationships (ρ) between measures taken at the same time point.

Figure 2.

Adjusted* HAD-D Scores Over Time Note. *HAD-D scores at Weeks 4 through Follow-Up (Week 16) represent model-adjusted (adjusting for baseline HAD-D and gender) means and standard errors. Week 0 mean HAD-D score is unadjusted.