Association between cannabis use and major depressive disorder: a population-based cross-sectional study

Major depressive disorder (MDD) is a chronic, recurrent psychiatric illness with challenging management, partly due to the heterogeneity of clinical presentations, unpredictable course and episodes, and variable treatment responses. Cannabis may alleviate depression by promoting glutamate, GABA, and dopamine, but results from previous studies remain controversial or inconsistent. In this study, we aimed to investigate the association between cannabis use and the prevalence and severity of MDD in adults. This study utilized data from the UK Biobank, with cannabis use as the exposure variable and depression as the outcome. Depression was ascertained using six distinct definitions, including broad clinical diagnosis, symptom-based criteria, self-reported depression, electronic health record-based diagnoses, and a strictly defined diagnostic category based on guideline criteria. C-reactive protein (CRP) levels and markers of biological aging were extracted from the database and analyzed as potential mediators. Both logistic and linear regression models were employed to examine the correlation. Subgroup analyses were used to explore potential effect modifiers while sensitivity analyses were used to ensure the robustness of the regression models. A total of 33,749 individuals were included in the final analysis, with 50.5% being male. Cannabis use was associated with a 27% increase in the odds of depression prevalence (adjusted odds ratio [OR] = 1.27; 95% confidence interval [CI] = 1.18–1.38). No significant association was observed between the frequency of cannabis use and the number of depression episodes. Subgroup analyses revealed that, among current smokers, cannabis use was not significantly associated with increased odds of depression (OR = 1.09; 95% CI = 0.89–1.35). CRP levels may mediate this relationship, whereas markers of biological aging did not. Sensitivity analyses conducted a priori demonstrated consistent results, supporting the robustness of these findings. Cannabis use is associated with elevated odds of depression, with a comparatively attenuated impact observed among current smokers. However, the quantity of cannabis consumed did not correlate with the number of depression episodes. Further research employing longitudinal cohort studies or controlled clinical trials is needed to further inform evidence-based depression management strategies.