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Psilocybin-assisted massed cognitive processing therapy for chronic posttraumatic stress disorder: Protocol for an open-label pilot feasibility trial

Shakila Meshkat, Wendy Lou, Rakesh Jetly, Venkat Bhat, Richard J. Zeifman, Kathleen E. Stewart, Reinhard Janssen-Aguilar, Candice M Monson

PLoS One January 17, 2025 DOI: 10.1371/journal.pone.0313741 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Open-label pilot study Randomized Peer reviewed
Sample size 15
Population Patients with chronic PTSD
Interventions Psilocybin Cognitive processing therapy
Dose 25 mg
Duration 7-day intervention, 12-week follow-up
Topics Psilocybin
Keywords Posttraumatic stress Cognition Cognitive processing therapy Cognitive behavioral therapy Hallucinogen
Citations 10
Registration NCT06386003
Key points This trial will generate preliminary data on the feasibility, tolerability, and efficacy of psilocybin-assisted massed CPT for treating chronic PTSD.

Abstract

Background: Posttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches. Preliminary evidence supports the potential therapeutic action of psilocybin to alleviate PTSD symptoms. This open-label pilot study aims to evaluate the feasibility, tolerability, and preliminary efficacy of a single dose 25 mg psilocybin in combination with one week of massed CPT in patients with chronic PTSD.

Method: Fifteen participants with chronic PTSD will undergo 12 CPT sessions, two psilocybin-related psychotherapy sessions, and one psilocybin dosing session over a 7-days period. The primary outcomes are feasibility and tolerability, which will be measured by recruitment rates, withdrawal, data completion, adherence, number and nature of adverse events. Secondary objectives include assessing the preliminary efficacy of psilocybin-assisted CPT in reducing PTSD severity, self-reported treatment outcomes and exploring putative mechanisms of change. Participants will be monitored weekly for 12 weeks post-treatment and passive data relevant to mental health and well-being will be collected using a wearable device.

Discussion: This trial will generate important preliminary data on the use of psilocybin-assisted CPT for treating PTSD. The findings will guide the design of a multi-site, large-scale randomized control trial to more rigorously assess the efficacy of this intervention. De-identified data from this study will be available upon request after publication of the results. This study represents a promising and innovative approach to PTSD treatment, potentially offering an alternative therapeutic option for individuals unresponsive to conventional therapies. Trial registration ClinicalTrials.gov NCT06386003 .

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