A long, strange trip: Ketamine treatment in psychiatry.
David Nutt, Celia J. A. Morgan, David Erritzøe, Kyle T. Greenway, Allan H. Young
Journal of Psychopharmacology October 27, 2025 DOI: 10.1177/02698811251379393 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Historical analysis Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Powerful compound Anesthetic Mental health treatment Depression treatment Severe depression Mood disorders Challenging psychiatric conditions Novel therapies Promising new frontier Surprising discovery Rapid relief Quick significant relief |
| Citations | 2 |
| Key points | Argues that ketamine's large safety margin regarding respiratory depression, combined with its analgesic properties, has made it widely used globally, especially in sub-Saharan Africa, where mechanically ventilated anesthesia is often not feasible. It also recounts the drug's history, from its first human testing 60 years ago as a safer anesthetic alternative to PCP to its use as a "buddy drug" during the Vietnam War. |
Abstract
It is 60 years since ketamine was first tested in humans as an alternative but safer anaesthetic to PCP (phencyclidine) (Corssen and Domino 1966). It became widely used as the “buddy drug” for combatants in the Vietnam War: because of its great safety margin, it could be injected into wounded personnel by their buddies to relieve pain before the arrival of the medical team. Because of ketamine’s great safety margin in terms of respiratory depression, plus its analgesic properties, it is widely used all over the world in places where mechanically ventilated anaesthesia for surgery is often not feasible, especially sub-Saharan Africa.
Comparable studies
Other theoretical and historical papers on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. | 2014 | Historical analysis | |
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Neuroscience and the Near-Death Experience: Roles for the NMSA-PCP receptor, the sigma receptor and the endopsychosins | 1990 | Theoretical or philosophical paper | |
| A unified model of ketamine's dissociative and psychedelic properties. | 2022 | Theoretical or philosophical paper | |
| An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression. | 2021 | Theoretical or philosophical paper |
Citations in the library
Cited by 3
- Ketamine as a Rapid-Acting Antidepressant: A Scoping Review of Mechanisms and Efficacy in Treatment-Resistant Depression. Psychopathology March 27, 2026
- Ketamine: reclassification alone will not reduce harms BMJ February 3, 2026
- Feeling safe: an empirical-ethical analysis of vulnerability in (es)ketamine treatment BMC Medical Ethics October 18, 2026
Cites 32
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
and 27 more in the library