Using Cannabis and Opioids Together Was Linked to Less Suicidal Risk Than Expected in Women
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Cannabis + opioid co-use showed sub-additive (not additive) suicide risk, especially in women
- Evidence Grade:
- 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.
- Study Age:
- Published in 2025.
- Original Title:
- Gender differences in non-fatal suicidal behaviors linked to concurrent use of cannabis and opioids.
- Published In:
- Journal of psychiatric research, 191, 170-176 (2025)
- Authors:
- Nayeem, Nawar(3), Wang, Samantha Sijing, Naidu, Aniketh, Messias, Erick, Lin, Ping-I
- Database ID:
- RTHC-07243
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
What does sub-additive risk mean?
If cannabis use and opioid use each carry a certain suicide risk individually, additive risk would mean their combined risk equals the sum. Sub-additive means the combined risk was actually less than the sum of the individual risks, suggesting the two substances may interact in ways that partially offset each other's association with suicidality.
Does this mean cannabis is protective against opioid-related suicidality?
The study found a statistical interaction, not proof of a protective effect. Multiple explanations exist, including unmeasured confounders, different populations choosing to co-use, or biological interactions between the substances. Much more research is needed before any protective claim could be made.
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Cite This Study
https://rethinkthc.com/research/RTHC-07243APA
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
MLA
Nayeem, Nawar, et al. "Gender differences in non-fatal suicidal behaviors linked to concurrent use of cannabis and opioids.." Journal of psychiatric research, 2025. https://doi.org/10.1016/j.jpsychires.2025.09.046
RethinkTHC
RethinkTHC Research Database. "Gender differences in non-fatal suicidal behaviors linked to..." RTHC-07243. Retrieved from https://rethinkthc.com/research/nayeem-2025-gender-differences-in-nonfatal
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.