NCT07104916

Mindfulness-based Psilocybin Therapy for PTSD

A Pilot Mechanistic RCT of Psilocybin With Mindfulness-based Therapy vs Support for Posttraumatic Stress Disorder (PTSD)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Anthony P King · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The goal of this study is to learn how psilocybin delivered with mindfulness-based therapy may help symptoms of posttraumatic stress disorder (PTSD). This is an assessor-blinded, randomized, controlled study in participants with PTSD. The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using EEG/EMG and multimodal MRI measures after administration of one oral dose of psilocybin, accompanied either with standard "psychological support" only; or with standard support plus Mindfulness-based Cognitive Therapy (MBCT).

Detailed description

Many patients with PTSD do not respond or have an incomplete response to treatment with currently available medications that are FDA-approved for PTSD, and/or do not respond to psychotherapies for PTSD. The use of psychedelics (e.g. psilocybin) is being investigated as a new approach to improve symptoms in patients with PTSD and depression, however their mechanism of action is still not well understood. Furthermore, while psychedelics are usually administered in the context of psychological support ("psychedelic assisted therapy", PAT) the kinds of support therapy used and possible interactions with drug with therapy effects is not well understood. This study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity, assessed using electroencephalography (EEG) / electromyography (EMG) and functional magnetic resonance imaging (fMRI) /diffusion-weighted magnetic resonance imaging (DWI), after administration of one oral dose of 25 mg synthetic Psilocybin delivered in the context of either non-directive psychological support only (the most common approach for PAT) or in combination with psychological support plus an active form of psychotherapy called Mindfulness-based Cognitive Therapy (MBCT). Up to 30 participants will be enrolled altogether. The initial phase of this study will be an open label administration of 25 mg synthetic Psilocybin combined with standard "PAT psychological support" plus MBCT in ten participants with PTSD, to allow us to pilot this new intervention package. In the next phase of the study, we will randomly assign twenty participants with PTSD into two groups: one group receiving 25 mg of synthetic Psilocybin (open label) combined with standard "PAT support" only, and one group receiving 25 mg of synthetic Psilocybin (open label) combined with standard "support" plus active form MBCT psychotherapy. In both groups, psychological support will be provided before, during and after the administration session. The MBCT group will also receive bi-weekly individual MBCT sessions and will be invited to complete daily homework, as per the MBCT protocol. Assessments performed at Baseline and on Day 2 and Day 28 after administration will include EEG/EMG, MRI, clinician-administered scales (CAPS-5, MADRS, C-SSRS) and self-report questionnaires to assess PTSD, depression and anxiety symptoms, cognitive testing, self-report questionnaires to evaluate the psychedelic effects of synthetic Psilocybin administration, and blood collection for the Gsα-AC biomarker assay.

Conditions

• Post Traumatic Stress Disorder
• Depression - Major Depressive Disorder

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Psilocybin + MBCT therapy	The experimental arm has psilocybin with support and MBCT sessions.
COMBINATION_PRODUCT	Active Comparator: Psilocybin with Support Only	The active comparator has psilocybin with support only.

Timeline

• Start date: 2026-05-01
• Primary completion: 2029-09-01
• Completion: 2029-12-01
• First posted: 2025-08-05
• Last updated: 2026-03-03

Regulatory

• FDA-regulated drug study