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

Background: 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.