The collective lie in ketamine therapy: a call to realign clinical practice with neurobiology
Charles Miller, Bárbara Lopes, Anna Mccurdy
Frontiers in Psychiatry September 22, 2025 DOI: 10.3389/fpsyt.2025.1610335 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Intervention | Ketamine-assisted psychotherapy |
| Topics | Ketamine Esketamine |
| Keywords | Clinical practice Dissociative Narrative review Mental health Function biology Psychotherapist Mechanism biology Cognitive science Medline |
| Key findings | The acute dissociative experience in ketamine-assisted psychotherapy is neither necessary nor sufficient for therapeutic success; lasting improvement requires plasticity-driven reorganization in the days following administration. |
Abstract
In recent years, ketamine therapy has become increasingly entangled with psychedelic culture, leading to widespread misinterpretation of its therapeutic mechanism. This manuscript challenges the prevailing narrative that positions ketamine as a consciousness-expanding agent or psychotherapy enhancer, highlighting the discord between this view and ketamine's well-established neurobiological function as an N-methyl-D-aspartate (NMDA) receptor antagonist that promotes neuroplasticity. Drawing on recent research and clinical data, the article argues that the acute dissociative experience often emphasized in ketamine-assisted psychotherapy (KAP) is neither necessary nor sufficient for therapeutic success. Instead, it describes how meaningful, lasting improvement in mental health outcomes requires plasticity-driven reorganization in the days following ketamine administration, not from insights gleaned during dissociation. By prioritizing subjective experience over biological timing, current KAP practitioners risk distorting memory, reinforcing maladaptive narratives, and undermining the potential of psychoplastogenic treatments. This article calls for a shift toward evidence-based protocols that align clinical practice with neurophysiology, advocating for greater education, standardization, and scientific rigor in ketamine therapy.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cites 16
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Ketamine: a paradigm shift for depression research and treatment Neuron March 1, 2019
- Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine as Adjunctive Therapy in Treatment-Resistant Depression (TRD) Molecular Psychiatry October 3, 2018
and 11 more in the library