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Mindfulness-based Psilocybin Therapy for PTSD | Clinical Trials | Clareo Health

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Mindfulness-based Psilocybin Therapy for PTSD

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

NCT07104916•Anthony P King

View on ClinicalTrials.gov

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.

Eligibility

Age

21 - 65 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Participant is assigned female or male at birth.
•2. Participant is aged between 21 to 65 years, inclusive, at Screening.
•3. Participant has a BMI of 18 to 35 kg/m2, inclusive, at Screening.
•4. Participant is ≥60 kg.
•5. Participant has a diagnosis of PTSD (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition \[DSM-5\] established through a clinician interview that includes the Mini-International Neuropsychiatric Interview \[MINI\]) and CAPS-5.
•6. PTSD severity moderate to severe based on CAPS score ≥24.
•7. Depression severity moderate to severe based on MADRS score ≥21.
•9\. Participant has been on a stable dose (no more than 50% change) of antidepressant medication (SSRI) in the last month prior to Screening.
•10\. Participants capable of producing sperm must use a condom during the trial and for 3 months after their dose of trial medication, if their partner is a person of childbearing potential. In addition, their partner of childbearing potential must use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) from dosing until 3 months following dosing.
•11\. Participants of childbearing potential must agree to use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) in combination with use of a condom by a partner who is capable of producing sperm, during the trial and for 3 months after dosing. Such participants must have a negative pregnancy test at Screening and Day 1.
+2 more criteria

Exclusion Criteria

•1. Taking the medications buspirone or venlafaxine in past month
•2. Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder or brief psychotic disorder; current or previous history of bipolar disorder, or current personality disorder (as determined by MINI at Screening).
•3. Clinically significant risk of suicidality, as determined through a comprehensive psychiatric interview that incorporates the Columbia Suicide Severity Rating Scale (CSSRS); a score of 4 or higher on the suicidal ideation subscale of C-SSRS (past 6 months) or any suicidal behaviour (lifetime), would be exclusionary.
•4. History of substance use disorder within the 12 months, as assessed by a structured clinical interview (Mini International Neuropsychiatric Interview \[MINI\], Version 7.0.2) or determined by self-report, or intake of \>21 units of alcohol weekly, and the inability to refrain from alcohol use from 48 hours before Screening and each scheduled visit until discharge from the study site. One unit is equivalent to a 285 mL glass of full-strength beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine.
•5. Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressant, other non-SSRI or non-SNRI antidepressants (e.g. bupropion, mirtazapine, etc), an antipsychotic or a mood stabilizer.
•6. Exposure to psilocybin, or any other psychedelics, such as ayahuasca, mescaline, LSD or peyote more than 10 times in the last 10 years, or any psychedelic use within 6 months prior to Screening.
•7. Use of psychotropic medicine/supplement (or medicine/supplement that would interact with psilocybin) during the 28 days before dosing. Participants may take a stable chronic dose of antidepressant medication(s) and/or sedatives/hypnotics. The Investigator and study team may review medication on a case-by-case basis to determine if its use would compromise participant safety or interfere with study procedures or data interpretation.
•8. Family history of schizophrenia or schizoaffective disorder (first degree relatives), or bipolar disorder type 1 (first degree relatives).
•9. Clinically relevant history of abnormal physical health interfering with the study as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including \[but not limited to\], neurological, endocrine, cardiovascular, respiratory, gastrointestinal (including dyspepsia or gastroesophageal reflux disease), hepatic, or renal disorder).
•10. Participant has a presence or relevant history of any of the following medical conditions: organic brain disorders (e.g., epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmal disease, brain tumor or other medical conditions associated with seizures or convulsions).
+20 more criteria

Key Dates

Start Date

May 1, 2026

Primary Completion Date

September 1, 2029

Completion Date

December 1, 2029

Last Updated

March 3, 2026

Enrollment

ESTIMATED participants

Conditions

Post Traumatic Stress DisorderDepression - Major Depressive Disorder

Interventions

Psilocybin + MBCT therapy

COMBINATION_PRODUCT

Active Comparator: Psilocybin with Support Only

COMBINATION_PRODUCT

Contacts

Anthony King, PhD

CONTACT

614 688-9537 anthony.king@osumc.edu

Arushi Badola, BS

CONTACT

614 688-9537 arushi.badola@osumc.edu

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RECRUITINGNA

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 3, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Mindfulness-based Psilocybin Therapy for PTSD

Inclusion Criteria

Exclusion Criteria

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