Using cannabis while receiving prescribed opioids was associated with an increased risk for adverse outcomes, according to results of a study published in JAMA Network Open.

Investigators from the University of California, San Francisco sourced data for this study from Veteran’s Affairs claims. Between 2014 and 2019, patients (N=297,620) who were receiving any prescribed opioid analgesic for nonend-of-life or noninpatient cancer care indications were screened for cannabis use in urine. Mortality and outcomes were evaluated at 90 and 180 days on the basis of cannabis co-use and duration of opioid use. Propensity matching and weighting approaches were used to balance for cohort differences.

Patients did (n=30,514) and did not (n=267,106) test positive for cannabis. The cannabis users and nonusers had a mean age of 57.8 (SD, 10.5) and 62.3 (SD, 12.3) years (P <.001), 94.3% and 92.7% were men (P <.001), 75.6% and 79.5% were White (P <.001), 4.2% and 3.0% had opioid use disorder (P <.001), and Charlson comorbidity index scores were 2.50 (SD, 1.91) and 3.33 (SD, 2.34) points (P <.001), respectively.


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In a randomly assigned sample of 1219 veterans, cannabis co-use was observed to be more common among individuals with substance and/or alcohol use-related behaviors, adverse outcomes related with opioid use, and clinician actions related with opioid use (all P ≤.01). The cannabis cohort was also more likely to test positive for other substances, such as cocaine, request specific opioid doses, request early opioid refills, escalate opioid dosage without authorization, and to self-harm compared with controls.

In the propensity-weighting analysis, cannabis use did not increase risk for mortality at 90 or 180 days among patients with opioid use in the past 90 days (both P ≥.36) or with long-term use (both P ≥.09). Risk for the composite outcome of emergency department visit, hospitalization, or all-cause mortality was associated with co-use of opioids and cannabis among patients with short-term opioid use at 90 (hazard ratio [HR], 1.05; 95% CI, 1.01-1.07; P =.001) and 180 (HR, 1.04; 95% CI, 1.01-1.06; P =.002) days as well as long-term use at 90 (HR, 1.05; 95% CI, 1.02-1.09; P =.003) and 180 (HR, 1.05; 95% CI, 1.02-1.09; P =.002) days.

Among the subset of patients aged 65 years and older, no significant associations between outcomes and opioid and cannabis concomitant use were observed among those who had short-term opioid use. Among the patients with long-term opioid use, cannabis co-use was associated with increased mortality at 90 days (HR, 1.55; 95% CI, 1.17-2.04) but not at 180 days (HR, 1.17; 95% CI, 0.95-1.44). No associations with the composite outcome were observed.

Similar trends were observed in the propensity-matching analyses.

The results of this study may not be generalizable for nonveteran populations.

Study authors concluded, “Patients engaging in concomitant cannabis and prescription opioid use were a higher-risk group, and our findings suggest that they may benefit from closer monitoring, counseling, and screening for substance use disorders.”

This article originally appeared on Psychiatry Advisor