Cannabis use did not reduce mortality in veterans on opioids, and increased risk in older adults

Among nearly 300,000 veterans prescribed opioids, cannabis use did not reduce mortality overall but was associated with increased 90-day mortality in adults over 65 on long-term opioid therapy.

Keyhani, Salomeh et al.·JAMA network open·2022·Strong EvidenceRetrospective Cohort
RTHC-03955Retrospective CohortStrong Evidence2022RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Retrospective Cohort
Evidence
Strong Evidence
Sample
N=297,620

What This Study Found

Cannabis use was not associated with all-cause mortality at 90 or 180 days in the overall population or among those on long-term opioid therapy. However, cannabis was associated with a small increased risk of composite adverse outcomes (ED visits, hospitalization, death). Among adults 65 and older on LTOT, cannabis use was associated with a 55% increased 90-day mortality risk (HR 1.55).

Key Numbers

297,620 veterans. 30,514 cannabis users. Overall mortality HR: 1.07 (90-day, NS), 1.00 (180-day, NS). Composite outcome HR: 1.05 (90-day), 1.04 (180-day). Adults 65+ on LTOT: 90-day mortality HR 1.55 (95% CI 1.17-2.04).

How They Did This

Cohort study of 297,620 veterans with urine drug screening (2014-2019) who received opioid prescriptions through the VA system. Propensity score weighting reduced confounding. Cox regression estimated hazard ratios for 90- and 180-day outcomes.

Why This Research Matters

Cannabis has been proposed as an opioid-sparing therapy that could reduce opioid-related deaths. This large VA study found no such mortality benefit and identified increased risk in the oldest patients, challenging the opioid-sparing narrative.

The Bigger Picture

The absence of a mortality benefit undermines one of the key arguments for cannabis as an opioid adjunct. The finding of increased risk in older adults on long-term opioids is particularly concerning given this is a rapidly growing demographic of cannabis users.

What This Study Doesn't Tell Us

Observational study cannot establish causation. Urine drug screening captures any recent use, not dose or frequency. Veterans may not represent the general population. Cannot distinguish therapeutic from recreational cannabis use.

Questions This Raises

  • ?Why are older adults on long-term opioids at higher mortality risk with cannabis?
  • ?Could drug interactions between cannabis and opioids explain the increased risk in seniors?

Trust & Context

Key Stat:
55% increased mortality risk in seniors on long-term opioids
Evidence Grade:
Large VA cohort with propensity score adjustment and biologically verified cannabis exposure, published in JAMA Network Open.
Study Age:
Published in 2022, covering 2014-2019.
Original Title:
Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids.
Published In:
JAMA network open, 5(12), e2247201 (2022)
Database ID:
RTHC-03955

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-ControlFollows or compares groups over time
This study
Cross-Sectional / Observational
Case Report / Animal Study

Looks back at existing records to find patterns.

What do these levels mean? →

Frequently Asked Questions

Does cannabis reduce the risk of opioid overdose death?

This study of nearly 300,000 veterans on opioids found no reduction in mortality associated with cannabis use. In adults over 65 on long-term opioids, cannabis was actually associated with increased mortality.

Is it safe to use cannabis while taking opioids?

While cannabis did not increase mortality for most opioid users in this study, it was associated with a small increase in ER visits and hospitalizations, and a 55% increase in 90-day mortality among adults 65 and older on long-term opioid therapy.

Read More on RethinkTHC

Cite This Study

RTHC-03955·https://rethinkthc.com/research/RTHC-03955

APA

Keyhani, Salomeh; Leonard, Samuel; Byers, Amy L; Zaman, Tauheed; Krebs, Erin; Austin, Peter C; Moss-Vazquez, Tristan; Austin, Charles; Sandbrink, Friedhelm; Bravata, Dawn M. (2022). Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids.. JAMA network open, 5(12), e2247201. https://doi.org/10.1001/jamanetworkopen.2022.47201

MLA

Keyhani, Salomeh, et al. "Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids.." JAMA network open, 2022. https://doi.org/10.1001/jamanetworkopen.2022.47201

RethinkTHC

RethinkTHC Research Database. "Association of a Positive Drug Screening for Cannabis With M..." RTHC-03955. Retrieved from https://rethinkthc.com/research/keyhani-2022-association-of-a-positive

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.