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Peer-reviewed article

Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?

Levinstein MRiD, Budinich RCiD, Bonaventura JiD, Schatzberg AF, Zarate CA Jr, Michaelides MiD

The American journal of psychiatryJan 15, 202544 citationsDOI: 10.1176/appi.ajp.20240378

Abstract

Ketamine is a racemic compound and medication comprised of (<i>S</i>)-ketamine and (<i>R</i>)-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders such as anxiety, obsessive-compulsive, and opioid use disorders. Despite its complex pharmacology, ketamine is referred to as an <i>N</i>-methyl-d-aspartate (NMDA) receptor antagonist. In this review, the authors argue that ketamine's pharmacology should be redefined to include opioid receptors and the endogenous opioid system. They also highlight a potential mechanism of action of ketamine for depression that is attributed to bifunctional, synergistic interactions involving NMDA and opioid receptors.

Topics & conditions

Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.

KetamineDepressionAnxietyOCD

Keywords

PsychopharmacologyAntidepressantsKetamine/esketamine

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