Higher Prevalence of Non-Fatal Overdose with Opioid and Stimulant Use Compared to Use of Opioids Alone

Background Fatalities from accidental drug overdose remain a major public health crisis in both the United States and Canada. Prior non-fatal overdose is an important risk factor for subsequent fatal overdose. Improved understanding of non-fatal overdose risk with respect to substance use patterns could support efforts to prevent overdose fatalities. Methods We examined associations between polydrug use and non-fatal overdose using data from four cohorts including people who use drugs (PWUD): ACCESS/VIDUS/ARYS (2018-2024), ALIVE (2018-2024), CNICS (2019-2025), and ROI (2018-2020). Cohorts collected data on drug use and non-fatal overdose in the past 6 months. Drug use was categorized as opioids only; opioids and stimulants; opioids and non-stimulant drugs; and non-opioid drugs. Relative risk regression models estimated prevalence ratios (PR) of nonfatal overdose by drug use adjusted for age, sex, race/ethnicity, and study time. Generalized estimating equations were used to examine repeated measures for ALIVE, CNICS, and ACCESS/VIDUS/ARYS. Random effects meta-analysis was used to obtain pooled estimates across cohorts. Results Among 7,573 PWUD, mean age was 44.7 (SD + 13.6) years; 71.4% were men, 60.8% reported White, 24.0% Black, and 7.1% Latine/Hispanic race/ethnicity; 44.1% had HIV; and 13.7% reported a non-fatal overdose at their last study visit. In pooled analyses, PWUD reporting using stimulants and opioids had greater non-fatal overdose prevalence, compared to opioids only (PR=2.26, 95%CI:1.56-3.27). Discussion The consistent increase in non-fatal overdose with opioids and stimulants compared to opioids alone across four diverse cohorts has implications for overdose prevention efforts.