Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm.
Henry A MacConnel, Mitch Earleywine, Steven Radowitz
Journal of Psychopharmacology 2025 DOI: 10.1177/02698811241286726 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective study Peer reviewed |
|---|---|
| Sample size | 117 |
| Population | Outpatients with elevated PTSD Checklist for DSM-5 scores |
| Intervention | Intravenous ketamine |
| Duration | At least six administrations |
| Topics | Ketamine PTSD Esketamine |
| Keywords | Ketamine-assisted psychotherapy Psychedelic Kap Trauma treatment |
| Citations | 5 |
| Key points | Intravenous ketamine in a psychedelic therapy paradigm was associated with large reductions in PTSD symptoms, with 75% of patients showing clinically meaningful improvement and no serious adverse events. |
Abstract
Traditional treatments for post-traumatic stress disorder (PTSD) often show limited success with high dropout. Ketamine, an N-methyl-D-aspartate antagonist known for rapid antidepressant effects, has decreased PTSD symptoms in some studies but not in others. Administering ketamine in ways that parallel psychedelic-assisted treatments-including preparatory, integration, sensory immersion, and psychotherapy sessions-could decrease PTSD symptoms meaningfully. A retrospective sample of 117 screened outpatients with elevated PTSD Checklist for DSM-5 (PCL-5) scores received intravenous ketamine in supportive environments. The protocol included preparation, intention-setting, and integration sessions accompanying at least six administrations. Administration sessions included eye shades and evocative music paralleling typical psychedelic therapy trials. Mean PCL scores decreased from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), d = 1.64. Patients tolerated treatment well, with no serious adverse events. Covariates, including age, gender, days between PCL assessments, number of psychiatric medications, and suicidal ideation were not significant moderators; concomitant psychotherapy did reach significance, d = 0.51. Of the 117 patients' final PCL scores, 88 (75.21%) measures suggested clinically meaningful improvement and 72 (61.54%) suggested remission of PTSD symptoms. Intravenous ketamine in supportive environments, with hallmarks of psychedelic therapy, preceded large reductions in PTSD symptoms. These results highlight ketamine's potential when delivered in this manner, suggesting environmental factors might account for some variation seen in previous work. Given the molecule's cost, minimal interaction with other psychiatric medications, and legal status, intravenous ketamine in a psychedelic paradigm may be a promising option for PTSD unresponsive to other treatments.
Comparable studies
Other observational and cohort studies on ketamine for PTSD, most cited first.
Citations in the library
Cited by 2
- Ketamine-assisted psychotherapies for mental disorders: A historical overview and systematic review. Clinical Psychology Review February 2, 2026
- Mindfulness, music, visual occlusion in ketamine therapy for depression: do they change outcomes? A qualitative and quantitative analysis of a randomized controlled trial Frontiers in Psychiatry September 2, 2025
Cites 31
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- Constructing drug effects: A history of set and setting Drug Science, Policy and Law 2017
- Predicting Responses to Psychedelics: A Prospective Study Frontiers in Pharmacology November 2, 2018
- Psychedelic Effects of Ketamine in Healthy Volunteers Anesthesiology 1998
and 26 more in the library