Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?
The American journal of psychiatry March 1, 2025 Marjorie R Levinstein, Reece C Budinich, Jordi Bonaventura et al. 49 citations
Ketamine, a racemic compound used as an anesthetic, analgesic, and recreational drug, is being investigated for treating refractory depression and comorbid conditions like anxiety, obsessive-compulsive disorder, and opioid use disorder. Although ketamine is traditionally classified as an NMDA receptor antagonist, this review argues its pharmacology should be redefined to include opioid receptors and the endogenous opioid system. The authors propose that ketamine's antidepressant effects may arise from bifunctional, synergistic interactions involving both NMDA and opioid receptors.