Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm

Abstract

Background: 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 others. Administering ketamine in ways that parallel psychedelic-assisted treatments—including preparatory, integration, sensory immersion, and psychotherapy sessions—could decrease PTSD symptoms meaningfully.Methods: A sample of 117 screened outpatients with elevated scores on the PTSD Checklist for DSM-5 (PCL-5) received intravenous ketamine in highly supportive environments. The protocol included sessions focusing on preparation, setting intentions, and integration for each of at least six administrations. Administration sessions included eye shades and evocative music in ways that paralleled facets of MDMA trials for PTSD.Results: Mean PCL scores decreased from 52.39 (SD = 11.90) to 29.42 (SD = 16.52; Cohen’s d = 1.60). 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 = 0.42.Conclusion: 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 that environmental factors might account for some of the variation that has appeared 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 new option for PTSD that has not responded to other treatments.