Opioid Overdose Risk Higher for Individuals Who Utilize Varied Routes of Administration

Opioid overdose is a significant cause of morbidity in the US. Previous studies have found that people who inject opioids are at higher risk of overdose than those who use other routes of administration. Researchers in Baltimore, Maryland used data from a cohort of individuals who have injected drugs to investigate the association between within-person variation in route of administration (i.e., injection, nasal inhalation, or smoking), and the risk of non-fatal overdose.

• The study included 1121 unique participants with 4396 visits between 2014 and 2022; the past six-month prevalence of self-reported overdose was 12 percent.
• Utilizing all three routes of opioid administration was associated with a higher risk of overdose compared with: injection alone (adjusted odds ratio [aOR], 2.4), nasal inhalation alone (aOR, 2.9), and injection and smoking (aOR, 4.2).
• The study found similar results for cocaine use via varied routes associated with an increased risk of self-reported overdose.

Comments: This study suggests that people utilizing varied routes of opioid administration have an increased risk of overdose. It makes sense that individuals who utilize only one route would have a more predictable response. It is possible that administration by varied routes is a marker for a more severe use disorder. Another potential factor is that overdose may prompt a change in route of administration. In any case, it would be reasonable to counsel individuals who utilize varied routes of opioid administration on the potential increased risk.

Darius A. Rastegar, MD

Reference: Lucia M, Feder KA, Kirk GD, et al. Association of route of drug administration with self-reported non-fatal overdose: a cohort study of Baltimore City adults who have injected drugs. Drug Alcohol Depend. 2025;277:112962.