Oliceridine: Examining the clinical evidence, pharmacology, and contested mechanism of action of the first FDA-approved biased opioid agonist

Oliceridine is the first Food and Drug Administration-approved biased opioid agonist, approved in 2020 for managing moderate to severe acute pain in adults in controlled clinical settings. The advantages of the drug are its potency and decreased opioid-related adverse effects compared to morphine. The rationale for its potency, and especially the decreased adverse effects, is its purported preferential G protein signaling over β-arrestin recruitment, favoring less opioid-related adverse effects. Further research has led to questions as to the actual mechanism of action of the drug, leading to additional questions about whether it is a genuinely biased opioid agonist. This paper examines the mechanism of action, pharmacology, adverse effects, and clinical evidence accumulated to date regarding its effectiveness as a potent analgesic.