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How ketamine works: An actionable hypothesis.

Roberto Malinow

Proceedings of the National Academy of Sciences of the United States of America May 5, 2026 DOI: 10.1073/pnas.2533728123 via PubMed

Summary

AI-generated from the abstract

Ketamine reduces depression and suicidality in treatment-resistant individuals, but its mechanism remains unknown. A new hypothesis proposes that synaptic and circuit plasticity underlies ketamine's effects, potentially leading to improved treatments for depression and other conditions.

Study at a glance

Characteristics Theoretical or philosophical paper Peer reviewed
Topics Depression Ketamine
Keywords Nmda
Key finding Ketamine's antidepressant effects may be explained by synaptic and circuit plasticity.

Abstract

Ketamine has been shown to reduce depression and suicidality in individuals resistant to treatment by other drugs. Exactly how ketamine works is not known. Here, I propose a new hypothesis that involves synaptic and circuit plasticity and may lead to enhanced efficacy in treating depression as well as other conditions.

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