Using Both Marijuana and Opioids Linked to Highest Depression Risk in Chronic Illness | Research

The takeaway

Among US adults with chronic conditions, co-use of marijuana and opioids was associated with nearly double the odds of major depression compared to using neither substance, exceeding the risk of either substance alone.

Primary care physicians, pain management specialists, psychiatrists, patients with chronic conditions, and public health researchers.

What the researchers found

Co-use of marijuana and opioids had the strongest association with major depressive disorder (AOR=1.92, 95% CI=1.45-2.50), followed by marijuana only (AOR=1.72) and opioid only (AOR=1.44), compared to no use of either substance — with 20.8% of co-users meeting MDD criteria.

Why it matters

People with chronic conditions often use opioids for pain and may add cannabis — this study reveals that combining them carries the highest depression risk, which clinicians should monitor.

The numbers in context

N=35,585; 8.5% co-use; MDD rates: co-use 20.8%, marijuana only 18.4%, opioid only 9.3%, neither 5.6%; adjusted ORs: co-use 1.92, marijuana 1.72, opioid 1.44; all significant

How the study worked

Cross-sectional analysis of 2022 National Survey of Drug Use and Health data from 35,585 US adults with chronic conditions, using Rao-Scott chi-square tests and multivariable logistic regression adjusting for demographics, behavioral, clinical, and social factors.

What this study cannot tell us

Cross-sectional design cannot establish causality; self-reported substance use; past-year timeframe may miss temporal relationships; opioid use includes both prescribed and non-prescribed; marijuana use may be for self-medication of existing depression.

How to read the evidence

Large nationally representative sample with comprehensive statistical adjustments, but cross-sectional design and self-report measures limit causal conclusions.

When this study was published

Published 2026; uses 2022 NSDUH data.

The bigger picture

As cannabis legalization expands and more chronic pain patients consider adding cannabis to opioid regimens, understanding the compounding mental health risks of co-use is critical for informed clinical decision-making.

Questions still open

Does co-use cause depression or do depressed individuals self-medicate with both substances? Would treating depression reduce co-use? Does the sequence of initiation (opioids first vs. cannabis first) affect risk?

Common questions

Does using marijuana and opioids together increase depression risk?

This large national study found that adults with chronic conditions who used both marijuana and opioids had nearly double the odds of major depression compared to those using neither, and higher risk than using either substance alone.

Is marijuana alone linked to depression in people with chronic conditions?

Yes — marijuana-only use was associated with 72% higher odds of major depression (AOR=1.72) compared to no substance use, though the study cannot determine if marijuana causes depression or if depressed individuals are more likely to use it.

Read the original research

Association of Combined Marijuana and Opioid Use with Major Depressive Disorder Among Adults with Chronic Conditions in the United States.

Substance use : research and treatment, 20, 29768357261423812

View on PubMed ↗Publisher’s paper ↗

Citation

Graham, Tiffany; Wiener, R Constance; Mitra, Sophie; Wang, Hao; Shen, Chan; Pedaprolu, Laskhmi; Sambamoorthi, Usha. (2026). Association of Combined Marijuana and Opioid Use with Major Depressive Disorder Among Adults with Chronic Conditions in the United States.. Substance use : research and treatment, 20, 29768357261423812. https://doi.org/10.1177/29768357261423812