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Background and Objectives: Bipolar disorder is a chronic condition affecting millions of people worldwide. Currently, there is some evidence to suggest that cannabis use during adolescence may be an environmental risk factor for its onset, however inconsistencies have been observed across the literature. Considering this, we aimed to assess whether early lifetime cannabis is associated with subsequent bipolar disorder in young adults between 18 and 22 years of age., Methods: Using data from the 1993 Pelotas (Brazil) birth cohort (n = 5249), cannabis exposure was examined at age 18 by self-report, and bipolar disorder diagnosis was measured at age 22 using the Mini International Neuropsychiatric Interview (MINI). In order to control the analysis, we considered socioeconomic status index, sex, skin color, physical abuse by parents and lifetime cocaine use., Results: A total of 3781 individuals were evaluated in 2015 aged 22 years, of whom 87 were diagnosed with the bipolar disorder onset after the age of 18. Lifetime cannabis use predicted bipolar disorder onset at 22 years old (OR 1.82, 95% CI [1.10, 2.93]), and the effect remained after adjusting for socioeconomic status, sex, skin color, and physical abuse by parents (OR 2.00, 95% CI [1.20, 3.25]). However, this association was attenuated to statistically non-significant after further adjustment for all available covariates, including lifetime cocaine use (OR 1.79, 95% CI [0.95, 3.19]). We also found similar results for early cocaine use, where the association with bipolar disorder onset did not maintain significance in the multivariate model (OR 1.35, 95% CI [0.62, 2.86]). Otherwise, when we considered cannabis or cocaine lifetime use as a unique feature, our findings showed that the adolescent exposure to cannabis or cocaine increased the odds by 1.95 times of developing bipolar disorder at 22 years age, even when controlling for all other study variables (OR 2.14, 95% CI [1.30, 3.47]). Finally, our models suggest that cocaine use may potentially exert a major influence on the effect of lifetime cannabis use on bipolar disorder onset, and that physical abuse by parents and sex may modify the effect of cannabis use for later bipolar disorder onset., Conclusion: Based on our findings, early cannabis exposure predicted bipolar disorder onset in young adults, but this association was confounded by cocaine use. Contrary to schizophrenia, cannabis as a sole exposure was not associated with bipolar disorder onset after adjusting for control variables., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)