The overdose crisis in North America is increasingly driven by illicitly manufactured fentanyl and other high-potency synthetic opioids, which are associated with severe and unpredictable opioid-induced respiratory depression (OIRD). Current pharmacologic strategies to prevent fatal overdose have largely emphasized downstream rescue through opioid antagonism (e.g., naloxone), leaving limited attention to upstream pharmacologic modification of respiratory risk. In this Opinion article, we argue that buprenorphine should be reframed not only as a treatment for opioid use disorder (OUD), but also as a pharmacologic modifier of OIRD risk in fentanyl-dominant drug markets. Drawing on its partial μ opioid receptor agonism, ceiling effect on respiratory depression, and exceptionally high receptor affinity, we describe how buprenorphine can displace full agonists while limiting respiratory suppression. We further situate this pharmacology within emerging population-level observations from North American fentanyl contexts, suggesting reduced overdose mortality among individuals receiving opioid agonist therapy, particularly buprenorphine. In fentanyl-dominant drug markets, reframing buprenorphine as a modifier of respiratory risk has direct implications for clinical messaging about overdose protection, medication selection for individuals with ongoing illicit opioid use, and policy approaches aimed at reducing opioid-related mortality.
Bahji et al. (Wed,) studied this question.