The ketamine chameleon: history, pharmacology, and the contested value of experience.
Danny Diep, Sara de la Salle, Julien Thibault Lévesque, Michael Lifshitz, Nicolas Garel, Kyle T. Greenway
Expert Review of Clinical Pharmacology March 1, 2025 DOI: 10.1080/17512433.2025.2459377 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Philosophy of mind Esketamine |
| Keywords | Anesthesia Biomedical psychiatry Dose-dependency Psychedelic psychiatry Ketamine therapy Psychedelic medicine Psychiatric treatment Medical applications Neuroscience research |
| Citations | 8 |
| Key findings | Ketamine's subjective effects are best understood as context-dependent, shifting between dissociative, dream-like, and psychedelic interpretations based on dose, language, and environment. |
Abstract
Since its synthesis in 1962, ketamine has been widely used in diverse medical contexts, from anesthesia to treatment-resistant depression. However, interpretations of ketamine's subjective effects remain polarized. Biomedical frameworks typically construe the drug's experiential effects as dissociative or psychotomimetic, while psychedelic paradigms emphasize the potential therapeutic merits of these non-ordinary states. Ketamine's psychoactive effects have inspired diverse interpretations. In this review, we trace the historical evolution of these perspectives - which we broadly categorize as 'dissociative,' 'dream-like,' and 'psychedelic' - and show how they emerged out of these clinical contexts. We highlight the influence of factors such as language, dose, and environmental context on ketamine's effects and therapeutic outcomes. We discuss potential mechanisms underlying these context-dependent effects and explore the broader clinical and research-related ramifications. Ketamine's subjective effects are undeniably powerful, yet their therapeutic significance remains debated. A nuanced, interdisciplinary approach is essential for maximizing ketamine's potential. Future research should focus on how explanatory models, treatment environments, and patient preparation can optimize ketamine's benefits while minimizing distress. We suggest that, rather than being a tiger to be tamed as its creator once described, ketamine may best be understood as a chameleon whose color shifts depending on its context.
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
Cited by 8
- Five-year outcomes of psilocybin-assisted therapy for Major Depressive Disorder Journal of Psychedelic Studies September 4, 2025
- A long, strange trip: Ketamine treatment in psychiatry. Journal of Psychopharmacology October 27, 2025
- Mystical Experiences as Catalysts in Ketamine-Assisted Psychotherapy: A Case Study Journal of Psychoactive Drugs July 3, 2026
- Bringing Psilocybin-Assisted Therapy to Palliative Oncology: Early Lessons from Real-World Implementation. Healthcare June 3, 2026
- New psychoactive substances (designer drugs): an approach to classification Neurology Bulletin March 23, 2026
and 3 more in the library
Cites 115
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
and 110 more in the library