OBJECTIVES: Bipolar disorder (BD) frequently co-occurs with substance use disorders (SUDs), including alcohol, cannabis, tobacco, stimulants, and opioids. Comorbid SUDs can worsen the clinical presentation of BD, contributing to more severe mood episodes, rapid cycling, and poorer recovery outcomes. However, the unique impacts of different SUDs on the BD clinical profile are less studied, potentially obscuring substance-specific effects on the course of illness and prognosis in BD. METHODS: We conducted a systematic review of the literature (PubMed, PsycINFO) and identified N = 48 clinical studies exploring the clinical effects of specific SUDs on BD symptomatology, course of illness, and treatment outcomes. RESULTS: Our findings revealed that cannabis use disorder (CUD) and alcohol use disorder (AUD) are the most studied SUDs in BD. Concurrent CUD is frequently associated with increased manic episodes, rapid cycling, psychosis, and earlier BD onset, with mixed findings for depressive episodes, suicidality, and treatment outcomes. AUD is frequently linked with worse depression outcomes and increased suicidality, with mixed findings for manic symptoms, rapid cycling, age of onset, psychosis, and treatment outcomes. Other SUDs, including cocaine, tobacco, opioids, and methamphetamine, were underexplored but were linked to increased suicidality, hospitalizations, and medication nonadherence. CONCLUSIONS: Specific clinical profiles were associated with different SUDs, which underscores the need for more research to improve our understanding and treatment of comorbid BD-SUDs. Further research exploring non-alcohol and non-cannabis SUDs and utilizing more rigorous methodological designs is needed to clearly elucidate these associations and advance substance-specific interventions in BD patients.
Garvie et al. (2026) studied this question.