How ketamine works: An actionable hypothesis.
Proceedings of the National Academy of Sciences of the United States of America May 5, 2026 Peer reviewed DOI: 10.1073/pnas.2533728123 via PubMed
Summary
Ketamine reduces depression and suicidality in individuals who do not respond to other treatments. The exact mechanism of action is unclear, but a new hypothesis suggests that it may involve synaptic and circuit plasticity, potentially improving treatment efficacy for depression and other conditions.
Study at a glance
| Population | individuals resistant to treatment by other drugs |
|---|---|
| Key finding | Ketamine has been shown to reduce depression and suicidality in individuals resistant to treatment by other drugs. |
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.