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.

Nayeem, Nawar et al.·Journal of psychiatric research·2025·Moderate EvidenceCross-Sectional
RTHC-07243Cross SectionalModerate Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Cross-Sectional
Evidence
Moderate Evidence
Sample
N=152,930

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)
Database ID:
RTHC-07243

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

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.

Read More on RethinkTHC

Cite This Study

RTHC-07243·https://rethinkthc.com/research/RTHC-07243

APA

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.