Psilocybin-Assisted Cognitive Processing Therapy for Chronic PTSD

NCT06386003 | Not Yet Recruiting Phase 2

• 1 other identifier: 23-230
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label trial evaluating feasibility, tolerability, safety and efficacy of psilocybin assisted cognitive processing therapy for chronic Posttraumatic Stress Disorder (PTSD).

Conditions

Post Traumatic Stress Disorder; PTSD; Chronic PTSD

Keywords

Post Traumatic Stress Disorder; Psilocybin; Cognitive Processing Therapy

Outcome Measures

Primary Outcomes (1)

• Feasibility and tolerability

  Recruitment rate, withdrawal rate, adherence rate, data completion rate, percentage of participants with severe adverse events.

  Up to 16 weeks

Secondary Outcomes (20)

• Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score

  Up to 16 weeks

• Posttraumatic stress disorder Checklist-5 (PCL-5)

  Up to 16 weeks

• Patient Health Questionnaire-9 (PHQ-9)

  Up to 16 weeks

• Generalized Anxiety Disorder Scale, 7-item (GAD-7)

  Up to 16 weeks

• Dissociative Experiences Scale II (DES-II)

  Up to 13 weeks

Other Outcomes (1)

• Effect on digital physiological passive data collected through the use of a wearable device

  Up to 16 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

Single dose of psilocybin 25mg + Massed cognitive processing therapy

Drug: Psilocybin

Interventions

Psilocybin DRUG

Participants will receive a single dose of psilocybin 25mg combined with 12 sessions of massed CPT, and 2 psychotherapy sessions related to psilocybin over 7 days.

Experimental

Eligibility Criteria

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

You may qualify if:

• Meet Diagnostic and Statistical Manual-5th edition (DSM-5) criteria for current PTSD with a duration of 6 months or longer assessed by study psychiatrist;
• Have a Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score of 50 or higher, indicating moderate to severe PTSD symptoms;
• Are willing to refrain from taking any psychiatric medications during the study period.

You may not qualify if:

• Are pregnant or nursing, or are women of child bearing potential who are not practicing an effective means of birth control;
• Have a history of or a current primary diagnosis of psychotic disorder, schizophrenia, delusional disorder, borderline personality disorder, schizoaffective disorder, bipolar disorder or, dissociative identity disorder;
• Have evidence or history of coronary artery disease or cerebral or peripheral vascular disease, hepatic disease with abnormal liver enzymes, or any other medical disorder judged by the investigator to significantly increase the risk of psilocybin administration;
• Have hypertension using the standard criteria of the American Heart Association (values of 140/90 or higher assessed on three separate occasions;
• History of seizure disorder;
• Uncontrolled insulin-dependent diabetes;
• Recent stroke, intracranial or subarachnoid hemorrhage (\< 1 year from signing of informed consent form \[ICF\]), recent myocardial infarction (\< 1 year from signing of ICF), clinically significant arrhythmia (\< 1 year from signing of ICF);
• Have liver disease with the exception of asymptomatic subjects with Hepatitis C who have previously undergone evaluation and successful treatment;
• Lifetime history of substance-induced psychosis;
• Lifetime history of substance use disorder with a hallucinogen;
• History of alcohol use disorder in the past 3 months.

Sponsors & Collaborators

• Unity Health Toronto: lead
• Toronto Metropolitan University: collaborator
• University of Ottawa: collaborator

Study Sites (1)

St. Michael's Hospital, Unity Health Toronto

Toronto, Ontario, Canada

Location

Related Publications (1)

• Meshkat S, J Zeifman R, Stewart K, Janssen-Aguilar R, Lou W, Jetly R, Monson CM, Bhat V. Psilocybin-assisted massed cognitive processing therapy for chronic posttraumatic stress disorder: Protocol for an open-label pilot feasibility trial. PLoS One. 2025 Jan 17;20(1):e0313741. doi: 10.1371/journal.pone.0313741. eCollection 2025.

  PMID: 39823496 DERIVED

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

Venkat Bhat

CONTACT

416-360-4000; venkat.bhat@utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: April 26, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 30, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)