REVIEW OF: Karandinos G et al, Addiction 2025;120(5):1040–1045
STUDY TYPE: Retrospective propensity score-matched cohort analysis

The prevalence of opioid smoking, which was once thought to be relatively rare, has been rising in recent years. Harm reduction advocates often recommend smoking as a safer alternative to injecting, but is it actually safer? In this study, researchers analyzed a large national sample of SAMHSA treatment data to find out.

Roughly 287,000 people entering substance use treatment who primarily smoked opioids were compared with a matched group who primarily injected. Mortality during the first year of treatment was compared between the two groups.

After controlling for opioid type, use severity, co-occurring substance use, housing, and demographics, mortality was lower among those who smoked compared to those who injected: 6.5 vs 9.7 deaths per 1,000 person-years, or about a one-third reduction in risk. This difference held across multiple sensitivity analyses, including daily users, higher-intensity treatment settings, and whether patients used opioids before or after fentanyl became highly prevalent in the illicit drug supply.

The study didn’t identify causes of death, but the difference likely reflects both lower overdose risk per use and fewer injection-related complications. Still, absolute risk remained substantial in both groups. For context, other studies have found that the mortality in the general population for comparable age groups is around 1–4 deaths per 1,000 person-years (Xu J et al, National Vital Statistics Reports 2025;74(4):1–138).

CARLAT TAKE
Smoking opioids appears less lethal than injecting, with about one-third lower mortality in this large treatment sample. That said, the absolute risk remains high; smoking is safer, not safe. When counseling patients, frame this as harm reduction, not reassurance. Continue to emphasize naloxone, avoiding use alone, and the importance of medication treatment.