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

**Authors:** Tiffany Graham, R. Constance Wiener, Sophie Mitra, Hao Wang, Chan Shen, Laskhmi Pedaprolu, Usha Sambamoorthi

PMC · DOI: 10.1177/29768357261423812 · Substance Use : Research and Treatment · 2026-02-23

## TL;DR

People with chronic conditions who use both marijuana and opioids are more likely to have major depression compared to those who use neither.

## Contribution

This study is the first to show a strong link between co-use of marijuana and opioids and increased risk of major depressive disorder in adults with chronic conditions.

## Key findings

- Co-use of marijuana and opioids was associated with the highest odds of major depressive disorder (MDD) compared to other groups.
- The adjusted odds ratio for MDD was 1.92 for co-users, 1.72 for marijuana-only users, and 1.44 for opioid-only users.
- Monitoring co-use of these substances is important to prevent worsening mental health in patients with chronic conditions.

## Abstract

Individuals with chronic conditions often use opioids for pain and the broadening legalization of marijuana and its potential analgesic effects may prompt some individuals to use marijuana as an additional option. Both substances have been individually linked to adverse effects on major depressive disorder (MDD), but little is known about their co-use. This study examined the association between co-use and MDD among US adults with chronic conditions.

This cross-sectional analysis used 2022 National Survey of Drug Use and Health data from 35 585 adults older than 18 years with chronic conditions. Participants were categorized into 4 groups: (1) co-use of marijuana and opioids, (2) opioid only, (3) marijuana only, and (4) neither in the past year. MDD was defined using DSM-5 criteria (⩾2 weeks of depressed mood or anhedonia with ⩾5 symptoms). Associations between substance use and MDD were assessed with Rao-Scott chi-square tests and multivariable logistic regression, adjusting for demographic, behavioral, clinical, and social determinants of health as well as COVID-19-related mental health and past-year benzodiazepine use.

Overall, 8.5% reported co-use; 26.1% reported opioid use and no marijuana use; and 10.9% reported marijuana use and no opioid use. Past year MDD was highest among those with co-use (20.8%) followed by marijuana only (18.4%); opioid only (9.3%); and neither (5.6%). In fully adjusted logistic regression, co-use had the strongest association with past year MDD (AOR = 1.92, 95% CI = 1.45, 2.50) followed by marijuana only (AOR = 1.72, 95% CI = 1.31, 2.26) and opioid only (AOR = 1.44, 95% CI = 1.14, 1.82) compared to the neither opioids nor marijuana group.

Co-use of opioids and marijuana is not uncommon among adults with chronic conditions and is associated with higher odds of MDD. These findings underscore the importance of monitoring substance use in people with chronic conditions, especially to detect co-use that may worsen mental health.

## Linked entities

- **Diseases:** major depressive disorder (MONDO:0002009)

## Full-text entities

- **Diseases:** chronic pain (MESH:D059350), depressed (MESH:D003866), kidney disease (MESH:D007674), heart disease (MESH:D006331), HIV or AIDS (MESH:D015658), emotion (MESH:D003072), Chronic Conditions (MESH:D002908), hypertension (MESH:D006973), Major (MESH:D004830), COVID (MESH:D000086382), cocaine dependence (MESH:D019970), obesity (MESH:D009765), COPD (MESH:D029424), MDD (MESH:D003865), opioid use disorder (MESH:D009293), disease (MESH:D004194), conditions (MESH:D020763), sleep problems (MESH:D012893), anhedonia (MESH:D059445), pain (MESH:D010146), addiction (MESH:D019966), Mental Disorders (MESH:D001523), diabetes (MESH:D003920), cancer (MESH:D009369), cirrhosis of the liver (MESH:D008103), hepatitis B or C (MESH:D006509), asthma (MESH:D001249), ORCID iD (MESH:C535742), anxiety (MESH:D001007)
- **Chemicals:** alcohol (MESH:D000438), psychoactive substances (-), benzodiazepine (MESH:D001569), cocaine (MESH:D003042)
- **Species:** Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097]

## Full text

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## Figures

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## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929868/full.md

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Source: https://tomesphere.com/paper/PMC12929868