Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence

Rationale: Cannabis use among people with mood disorders increased in recent years. While comorbidity between cannabis use, cannabis use disorder (CUD), and mood disorders is high, the underlying mechanisms remain unclear.

Objectives: We aimed to evaluate (1) the epidemiological evidence for an association between cannabis use, CUD, and mood disorders; (2) prospective longitudinal, genetic, and neurocognitive evidence of underlying mechanisms; and (3) prognosis and treatment options for individuals with CUD and mood disorders.

Methods: Narrative review of existing literature is identified through PubMed searches, reviews, and meta-analyses. Evidence was reviewed separately for depression, bipolar disorder, and suicide.

Results: Current evidence is limited and mixed but suggestive of a bidirectional relationship between cannabis use, CUD, and the onset of depression. The evidence more consistently points to cannabis use preceding onset of bipolar disorder. Shared neurocognitive mechanisms and underlying genetic and environmental risk factors appear to explain part of the association. However, cannabis use itself may also influence the development of mood disorders, while others may initiate cannabis use to self-medicate symptoms. Comorbid cannabis use and CUD are associated with worse prognosis for depression and bipolar disorder including increased suicidal behaviors. Evidence for targeted treatments is limited.

Conclusions: The current evidence base is limited by the lack of well-controlled prospective longitudinal studies and clinical studies including comorbid individuals. Future studies in humans examining the causal pathways and potential mechanisms of the association between cannabis use, CUD, and mood disorder comorbidity are crucial for optimizing harm reduction and treatment strategies.