A retrospective case series evaluating a rapid extended-release buprenorphine induction protocol without prior sublingual stabilization reported significant reductions in monthly opioid overdose rates alongside an absence of serious adverse events among individuals with opioid use disorder who use illicit fentanyl in shelter-based harm reduction settings.

Individuals diagnosed with opioid use disorder who use illicit fentanyl in shelter-based environments face substantial barriers to conventional medications for opioid use disorder. Standard clinical pathways frequently require stabilization on sublingual buprenorphine prior to administering extended-release injectable buprenorphine, a requirement that this low-barrier, virtual-care protocol sought to bypass without mandating opioid abstinence.

The study reviewed all twenty-one individuals who received at least one off-label injection of extended-release buprenorphine between October 1, 2023, and April 30, 2024, through Alberta’s Virtual Opioid Dependency Program. The clinical initiative operated in partnership with two harm reduction program sites offering supervised consumption services, shelter-based housing, or both. Program eligibility required a diagnosis of opioid use disorder under the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, high clinical risk for recurrent overdose, documented prior buprenorphine exposure without allergy, and no history of substance-induced seizures.

All twenty-one participants were actively using illicit fentanyl at intake, confirmed by self-report and verified against provincial electronic medical records, with seven participants reporting fentanyl use within four hours prior to injection. Under the evaluated care model, participants received 300 milligrams of extended-release buprenorphine within twenty-four hours of intake without preceding sublingual stabilization.

Primary outcomes evaluated included pre- versus post-treatment changes in monthly opioid overdose incidence rates, treatment retention, and adverse events, while secondary outcomes examined self-reported fentanyl use changes and adjunct medications. Following initiation, monthly overdose incidence rates decreased significantly from a pre-treatment mean of 0.87 overdoses per month to a post-treatment mean of 0.08 overdoses per month, evaluated using a Wilcoxon signed-rank test (Z = -3.54, p = 0.0004). Additionally, 62 percent of participants reported reduced fentanyl use after receiving treatment.

No serious adverse events or deaths occurred during the observation period, with two participants (10 percent) experiencing mild, self-resolving symptoms. In total, 57 percent of participants (twelve individuals) received at least one maintenance dose, 38 percent received two, 19 percent received three, and 10 percent received four maintenance doses, with an overall mean of 2.24 doses and 75 percent of those returning doing so within 42 days. The authors concluded that the rapid induction approach was safe and associated with significant overdose reductions in this setting, while noting that larger prospective studies remain necessary to confirm findings and optimize protocols.

Subject of Research: Rapid extended-release buprenorphine induction in shelter-based harm reduction

Article Title: Rapid extended-release buprenorphine induction without sublingual stabilization in a shelter-based harm reduction setting for high-risk fentanyl use: a retrospective case series

Article References: Zobell, J. S., Davis, L., Hoffman, L. A., Atkinson, H., Orukpe, I., Guest, L., Aboud, H., Ghauri, I., & Day, N. (2026). Rapid extended-release buprenorphine induction without sublingual stabilization in a shelter-based harm reduction setting for high-risk fentanyl use: a retrospective case series. Harm Reduction Journal. https://doi.org/10.1186/s12954-026-01538-3

Image Credits: AI Generated

DOI: 10.1186/s12954-026-01538-3

Keywords: buprenorphine, opioid use disorder, harm reduction, fentanyl, extended-release buprenorphine, shelter health, overdose prevention, virtual care, Rapid, extended-release, induction, without