Dual Cannabis-Methamphetamine Use Doubles Bipolar Disorder Risk After Psychosis: A 25-Year Inpatient Cohort Study from Iran

ObjectiveThis study aimed to estimate transition rates from substance-induced psychosis (SIP) to schizophrenia or bipolar disorder, evaluate the risk associated with dual use of methamphetamine and cannabis, and identify predictors of chronicity among Iranian men. MethodsA 25-year retrospective cohort study (1999-2024) was conducted using clinical data from Shafa Hospital, a tertiary psychiatric referral center in Guilan Province, Iran. The study included 258 male inpatients aged [≥]17 years with SIP attributed to cannabis and/or methamphetamine use. Patients with a history of schizophrenia or bipolar disorder were excluded. Outcomes were validated using DSM-V criteria, and Kaplan-Meier survival curves and Cox proportional hazards models were employed for analysis. ResultsOver a median follow-up of 33 months, 37.6% of participants transitioned to schizophrenia (25.2%) or bipolar disorder (12.4%). The median time to conversion was shorter for bipolar disorder (13.4 months) compared to schizophrenia (26.6 months). Dual cannabis-methamphetamine use significantly increased the risk of bipolar disorder (p=0.008). Familial psychiatric history doubled the risk of schizophrenia (HR=4.29, 95% CI: 2.48-7.41) and tripled the risk of bipolar disorder (HR=3.89, 95% CI: 1.87-8.11). Recurrent hospitalizations were associated with increased risks for both schizophrenia (HR=1.34) and bipolar disorder (HR=2.64). The cumulative incidence of schizophrenia rose linearly to 67.6% at 10 years. ConclusionSIP poses a significant risk for the development of schizophrenia or bipolar disorder, particularly in cases involving dual-substance use, younger age, familial psychiatric history, and frequent hospitalizations. The findings underscore the need for targeted surveillance, early intervention, and long-term, risk-stratified care models in regions with rising methamphetamine use to reduce SIP-related morbidity