Association of Antidepressant and/or Benzodiazepine Use With Cannabis Frequency and Differences by Sex in Primary Care Patients With Depression and/or Anxiety

Background Cannabis use is increasingly prevalent among adults with depression and anxiety, raising concerns about potential interactions with prescribed antidepressant medication and/or benzodiazepines. Using data from a large, university health system in Los Angeles, this cross‐sectional study examined the association between having an active prescription of antidepressant medication and/or benzodiazepines and frequency of cannabis use by sex in adult primary care patients with depression and/or anxiety. Methods This analysis included 45,693 adult male and female patients with a current diagnosis of depression and/or anxiety (International Classification of Diseases, Tenth Revision [ICD‐10] codes: F41, F33) listed in their electronic health record (EHR). Among patients with a diagnosis, those with an active prescription for antidepressant medication and/or benzodiazepines were identified using EHR data. Cannabis use was assessed as part of routine patient self‐administered screening via the EHR‐based Tobacco and Cannabis Questionnaire (TCQ) from January 2021 to June 2023. Sex‐stratified multivariable ordinal logistic regression models assessed whether active antidepressant medication and/or benzodiazepine prescriptions were associated with increased cannabis use frequency. Models were adjusted for sexual identity, age, race/ethnicity, employment, and Charlson Comorbidity Index (CCI). Results Females comprised 67.5% of the sample of patients with depression and/or anxiety; 16.3% reported cannabis use for mental health symptoms. Cannabis use for mental health symptoms among males was 21.2%.Among those with depression and/or anxiety, 46.2% of females and 42.8% of males were prescribed antidepressant medication and/or benzodiazepines. Females with an active prescription for antidepressant medication and/or benzodiazepines had 1.32 times the adjusted odds of more frequent cannabis use (95% CI: 1.24–1.40) compared to those without a prescription. Among males, the adjusted odds ratio was lower at 1.14 (95% CI: 1.06–1.23), suggesting a significant difference by sex. Conclusions Findings indicate that cannabis use commonly occurs alongside prescribed mental health treatment, underscoring the need for primary care providers to routinely address cannabis and medication co‐use during clinical care.