Gender differences in non-fatal suicidal behaviors linked to concurrent use of cannabis and opioids

Cannabis and opioids are among the most misused substances in the U.S. Growing evidence suggests gender differences in how substance use impacts mental health, particularly non-fatal suicidal behaviors. This study investigates whether the joint effect of cannabis and opioid use on non-fatal suicidal behaviors differs between men and women METHODS: We extracted data on US citizens from the All of Us (AoU) Research Program (N = 152,930; ages 18-49) and used logistic regression models to assess whether cannabis and opioid uses and their interaction were associated with non-fatal suicidal behaviors (suicidal ideation, attempts, or self-harm), controlling for demographic and psychiatric variables RESULTS: In the study population, 3.2 % of participants used cannabis, 2.3 % used opioids, and 2.5 % experienced non-fatal suicidal behaviors. We found that the co-use of cannabis and opioids was associated with a smaller-than-expected increase in non-fatal suicidal behaviors overall and among women, suggesting an attenuated rather than additive risk (β = -0.58 overall; β = -0.87 in women; both p < 0.001). In men, however, this joint effect did not significantly differ from additivity (β = -0.29, p = 0.07), indicating a potential greater vulnerability CONCLUSIONS: These findings underscore gender-specific differences in the relationship between polysubstance use and suicidality, with implications for tailoring suicide risk screening and intervention programs. Understanding how cannabis and opioid co-use influences non-fatal suicidal behaviors differently across genders is crucial for developing targeted prevention efforts. Future research should explore the biological, psychological, and social mechanisms driving these disparities to inform more effective harm reduction strategies and mental health interventions.