How ketamine works: An actionable hypothesis.
Proceedings of the National Academy of Sciences of the United States of America May 5, 2026 DOI: 10.1073/pnas.2533728123 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Depression Ketamine Esketamine |
| Keywords | Nmda |
| Key points | Proposes that ketamine's antidepressant effects arise from 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.