REL-1017 (esmethadone; d-Methadone), a Rapid-Acting Antidepressant Has No Meaningful Opioid Abuse Liability in Nonclinical and Clinical Abuse Potential Studies

Henningfield J (presenter), Apseloff G, Gorodetzky C, Pappagallo M, Shram M, De Martin S, Fant R, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Bifari F, Folli F, Ribeiro S, Traversa S, Inturrisi CE, Manfredi PL

REL-1017 (esmethadone) is the opioid-inactive isomer of methadone and a novel uncompetitive NMDAR antagonist with efficacy in all tested models of depressive-like behaviour. In a Phase 2 clinical trial REL-1017 showed rapid, robust, and sustained efficacy as adjunctive treatment for Major Depressive Disorder (MDD) without opioid-like side effects. Phase 3 trials are in progress. Due to the high prevalence of substance use disorder among patients with MDD, we evaluated REL-1017 in nonclinical (rat) and human abuse potential (HAP) studies.

To be presented at the 84th CPDD Annual Scientific Meeting, June 11-15, 2022.