Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models

Oxa-iboga alkaloids are presented as ibogaine analogs designed to reduce ibogaine's cardiac safety risk while preserving strong anti-opioid effects. The study reports that oxa-iboga compounds do not show proarrhythmic adverse effects in primary human cardiomyocytes and act as potent kappa opioid receptor agonists. Pharmacologically, they have improved opioid-relevant efficacy in male rat models of opioid use disorder. In preclinical relapse and pain-related models, oxa-noribogaine induces long-lasting suppression of intake of morphine, heroin, and fentanyl after single-dose or short regimens, reverses opioid-induced hyperalgesia, and suppresses opioid drug seeking in rodent relapse paradigms. Mechanistically, the paper frames these compounds as mechanistically distinct from standard kappa opioid agonists, including atypical behavioral features despite KOR activity.