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

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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

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Funding

This study was supported by National Institutes of Health grants UG1DA013727, UG1DA015831, UG1DA020024, UG1DA013714, U10DA013045, HHSN271201200017C, K12HD055885, K24DA038240, K23AA025399, K23DA042935, K01DA036739, and T32DA035200.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, MSC 861, 67 President Street, Charleston, SC, 29425-8610, USA

    Rachel L. Tomko, Amanda K. Gilmore, Erin A. McClure, Lindsay M. Squeglia, Aimee L. McRae-Clark, Susan C. Sonne & Kevin M. Gray

  2. Department of Public Health Sciences, Medical University of South Carolina, MSC 861, 67 President Street, Charleston, SC, 29425-8610, USA

    Nathaniel L. Baker

  3. Department of Psychology, University of Kentucky, Lexington, KY, 40506, USA

    Caitlyn O. Hood

  4. College of Nursing, Medical University of South Carolina, MSC 861, 67 President Street, Charleston, SC, 29425-8610, USA

    Amanda K. Gilmore

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  1. Rachel L. Tomko
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Correspondence to Rachel L. Tomko.

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Conflict of interest

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.

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Tomko, R.L., Baker, N.L., Hood, C.O. et al. Depressive symptoms and cannabis use in a placebo-controlled trial of N-Acetylcysteine for adult cannabis use disorder. Psychopharmacology 237, 479–490 (2020). https://doi.org/10.1007/s00213-019-05384-z

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