A systematic review and meta-analysis of sex differences in cannabis use disorder amongst people with comorbid mental illness

ABSTRACT

Background

While males are more likely diagnosed with cannabis use disorder (CUD), females are more susceptible to developing and maintaining CUD. Yet, for both sexes, CUD is associated with high rates of comorbid mental illness (MI).

Objectives

To identify and compare sex differences in the prevalence of comorbid CUD amongst individuals with/without MIs.

Methods

This systematic review generated pooled odds ratios (OR) and 95% confidence intervals (CI) from 37 studies (including clinical trials, cohort, and case–control studies) among individuals with and without MIs, quantifying sex differences in rates of comorbid CUD. A meta-analysis was also completed.

Results

In the CUD-only group, males were twice as likely to have CUD than females (OR = 2.0, CI = 1.9–2.1). Among MIs, males were more likely than females to have CUD comorbid with schizophrenia (OR ~2.6, CI = 2.5–2.7) and other psychotic, mood, and substance use disorders (1> OR <2.2, CI = 0.7–2.6). The reverse association (females > males) was observed for anxiety disorders and antisocial personality disorder (OR = 0.8, CI = 0.7–1.0). Among females, MIs increased the likelihood of having CUD, except for psychotic disorders and depression. A meta-analysis was inconclusive due to high heterogeneity across studies. Thus, comparisons across MI groups were not possible.

Conclusion

While males are more likely to be diagnosed with CUD, there are important sex differences in the prevalence of CUD across MI diagnoses that should be taken into account when approaching CUD prevention and determining treatment efficacy.

KEYWORDS:

• Cannabis
• cannabis use disorder
• sex differences
• mental illness
• comorbidity
• schizophrenia
• depression
• bipolar disorder
• meta-analysis

Funding

This manuscript was supported in part by a CIHR Pre-Doctoral Award (to Ms Kozak), the Canada First Research Excellence Fund awarded to the Healthy Brains for Healthy Lives Initiative at McGill University (to Dr Rabin), NIDA grant R21-DA-043949 (to Dr George), NIDA grant R01-DA-047296 (to Dr Cooper), and the Semel Charitable Foundation (to Dr Cooper).

Disclosure statement

Dr George reports that he is a consultant for Frutarom, Novartis, and the Canadian Centre for Substance Use and Addiction in the last 12 months. Dr Cooper reports that she served on the scientific advisory board of FSD Pharma in the last 12 months.