Mindfulness-based Psilocybin Therapy for PTSD

NCT07104916 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY20250273
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Depression - Major Depressive Disorder; Post Traumatic Stress Disorder

Keywords

Psychedelic; functional MRI; Mindfulness-based Cognitive Therapy; Psilocybin; microstructural neuroplasticity

Outcome Measures

Primary Outcomes (4)

• Changes in parameter estimate of regional brain activity measured by fMRI after one dose of psilocybin in participants with PTSD

  Change in Blood oxygenation level dependent (BOLD) fMRI signal after task comparing PAT with MBCT group vs PAT with support only group

  Between Baseline and Time point 24 hours and 28 days post-Investigational Product

• Changes in region-to-region connectivity measured by fMRI after PAT with one dose of psilocybin in patients with PTSD

  Changes in resting state activity of brain areas comparing PAT with MBCT group vs PAT with support only group

  Between Baseline and Time point 24 hours and 28 days post-Investigational Product

• Changes in event related potentials (ERP) after PAT with one dose of psilocybin in participants with PTSD

  Change in ERP as assessed by Electroencephalography (EEG) after task comparing PAT+MBCT group and PAT with support only group

  Between Baseline and Time point 24 hours and 28 days post-Investigational Product.

• Changes in acoustic startle electromyographic (EMG) response after PAT with one dose of psilocybin in patients with PTSD

  Changes in acoustic startle magnitude measured by EMG after task comparing PAT + MBCT group and PAT with support only group

  Between Baseline and Time point 24 hours and 28 days post-Investigational Product

Secondary Outcomes (4)

• Changes in clinician-assessed PTSD Symptoms after PAT with one dose of psilocybin in patients with PTSD

  Baseline to 24 h and 28 days post IP

• Changes in clinician-assessed Depression Symptoms after PAT with one dose of psilocybin in patients with PTSD

  Baseline to 24 hours and 28 days post-Investigational Product (IP)

• Changes in Self-report PTSD Symptoms after PAT with one dose of psilocybin in patients with PTSD

  Baseline to 24 hrs and 28 days post IP

• Changes in Self-report Depression Symptoms after PAT with one dose of psilocybin in patients with PTSD

  Baseline to 24 hrs and 28 days post IP

Other Outcomes (2)

• Changes in Brain Microstructural Neuroplasticity after PAT with one dose of psilocybin in patients with PTSD

  Baseline 24 hours and 28 days post-Investigational Product (IP)

• Proteins and Biomarkers

  24 hours and 28 days post-Investigational Product (IP)

Study Arms (2)

Psilocybin with support + MBCT

EXPERIMENTAL

Participants will receive one oral dose of psilocybin (capsule), with PAT psychological support and MBCT sessions before, during, and after the psilocybin administration

Combination Product: Psilocybin + MBCT therapy

Psilocybin with support only

ACTIVE COMPARATOR

Participants will receive one oral dose of psilocybin (capsule), with PAT psychological support only sessions before, during, and after the psilocybin administration

Combination Product: Active Comparator: Psilocybin with Support Only

Interventions

Psilocybin + MBCT therapy COMBINATION_PRODUCT

The experimental arm has psilocybin with support and MBCT sessions.

Psilocybin with support + MBCT

Active Comparator: Psilocybin with Support Only COMBINATION_PRODUCT

The active comparator has psilocybin with support only.

Psilocybin with support only

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is assigned female or male at birth.
• Participant is aged between 21 to 65 years, inclusive, at Screening.
• Participant has a BMI of 18 to 35 kg/m2, inclusive, at Screening.
• Participant is ≥60 kg.
• 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.
• PTSD severity moderate to severe based on CAPS score ≥24.
• Depression severity moderate to severe based on MADRS score ≥21.
• \. Participant has been on a stable dose (no more than 50% change) of antidepressant medication (SSRI) in the last month prior to Screening.
• \. 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.
• \. 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.
• \. Participants of non-childbearing potential who are or were capable of producing eggs (ova) must be postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy or bilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for at least 12 months, and a serum follicle stimulating hormone (FSH) level in the menopausal range, unless the participant is taking hormone replacement therapy or is using hormonal contraception.
• \. Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• Taking the medications buspirone or venlafaxine in past month
• 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).
• 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.
• 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.
• 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.
• 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.
• Family history of schizophrenia or schizoaffective disorder (first degree relatives), or bipolar disorder type 1 (first degree relatives).
• 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).
• 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).
• Diagnosis of hypertension or arrhythmia.
• Clinically relevant abnormal heart rate (resting supine heart rate \>100 bpm) or blood pressure (resting supine systolic blood pressure (SBP) above 140 mmHg or diastolic blood pressure (DBP) above 90 mmHg) at screening. Screening supine SBP, DBP and heart rate for evaluation will be the average of 3 readings obtained after at least 5 minutes rest. Participants with abnormal vital signs which are out of range and deemed clinically significant by the Investigator at Day 1, following triplicate readings.
• Presence of clinically significant ECG abnormalities at the Screening visit, as defined by medical judgement.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 msec at Screening, following triplicate ECG readings.
• Hypothyroidism and/or current abnormal thyroid function tests. In case of uncertain or questionable screening thyroid function test results, the TSH test may be repeated once during screening. The TSH test must be reviewed to ensure that it is within normal limits before randomizing a participant into the study.
• Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), 12-lead ECG and vital signs, or physical findings at Screening. In case of uncertain or questionable results, tests performed during Screening may be repeated once to confirm eligibility or judged to be clinically irrelevant.

Sponsors & Collaborators

• Anthony P King: lead

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Central Study Contacts

Anthony King, PhD

CONTACT

614 688-9537; anthony.king@osumc.edu

Arushi Badola, BS

CONTACT

614 688-9537; arushi.badola@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a Phase II, randomized, assessor-blind study in participants with PTSD. The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using EEG/EMG and fMRI / DWI measures after administration of one oral dose of psilocybin, accompanied either with standard "psychological support" or with active therapy called MBCT.

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: August 5, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 3, 2026

Record last verified: 2026-02