Co-use of cannabis and opioids was associated with a smaller-than-expected increase in suicidal behaviors in women, suggesting an attenuated rather than additive risk, while men showed no significant deviation from additivity.
Addiction researchers, suicide prevention specialists, clinicians treating polysubstance use.
Cannabis + opioid co-use showed sub-additive (not additive) suicide risk, especially in women
What the researchers found
Cannabis and opioid co-use was associated with a smaller-than-expected (sub-additive) increase in non-fatal suicidal behaviors overall (interaction beta=-0.58, p<0.001) and especially in women (beta=-0.87, p<0.001). In men, the joint effect did not significantly differ from additivity (beta=-0.29, p=0.07), indicating potential greater vulnerability.
Why it matters
The finding that cannabis-opioid co-use produces a sub-additive rather than additive suicide risk, particularly in women, complicates simplistic assumptions about polysubstance use. It suggests the interaction between these substances and mental health is more nuanced than expected.
The numbers in context
n=152,930; 3.2% used cannabis; 2.3% used opioids; 2.5% experienced non-fatal suicidal behaviors; overall interaction beta=-0.58, p<0.001; women interaction beta=-0.87, p<0.001; men interaction beta=-0.29, p=0.07.
How the study worked
Logistic regression analysis of All of Us Research Program data (n=152,930, ages 18-49) examining whether cannabis and opioid use and their interaction were associated with non-fatal suicidal behaviors, controlling for demographic and psychiatric variables, stratified by gender.
What this study cannot tell us
Cross-sectional design cannot establish temporal order or causation. Self-reported substance use may underestimate actual co-use. The All of Us cohort may not be fully representative of the US population. Small effect sizes limit clinical significance. Cannot determine mechanisms of the sub-additive interaction.
How to read the evidence
Moderate: Large dataset from the All of Us Research Program with gender-stratified analysis, though cross-sectional design and self-reported measures limit causal interpretation.
When this study was published
Published in 2025.
The bigger picture
This study contributes to growing research on polysubstance use and mental health outcomes. The gender-specific finding adds complexity to substance use risk assessment and suggests that blanket approaches to polysubstance risk may miss important nuances.
Questions still open
- What mechanisms explain the sub-additive interaction between cannabis and opioids for suicidal behaviors? Is cannabis moderating opioid-related distress, or is some other confounding factor involved? Would these patterns replicate in other datasets?
Common questions
What does sub-additive risk mean?
Does this mean cannabis is protective against opioid-related suicidality?
Read the original research
Gender differences in non-fatal suicidal behaviors linked to concurrent use of cannabis and opioids.
Journal of psychiatric research, 191, 170-176
Citation
Nayeem, Nawar; Wang, Samantha Sijing; Naidu, Aniketh; Messias, Erick; Lin, Ping-I. (2025). Gender differences in non-fatal suicidal behaviors linked to concurrent use of cannabis and opioids.. Journal of psychiatric research, 191, 170-176. https://doi.org/10.1016/j.jpsychires.2025.09.046
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