Psilocybin-Assisted Cognitive Processing Therapy for Chronic PTSD

Psilocybin-Assisted Massed Cognitive Processing Therapy for Chronic Posttraumatic Stress Disorder: An Open-label Trial

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

Study Overview

• Status: Not yet recruiting
• Conditions: PTSD; Post Traumatic Stress Disorder; Chronic PTSD
• Intervention / Treatment: Drug: Psilocybin

Detailed Description

Current front-line treatments for Posttraumatic stress disorder (PTSD) are ineffective for up to half of patients, with serious medical and societal consequences. It is imperative to improve the efficacy of front-line treatment options, such as cognitive processing therapy (CPT). CPT is an effective treatment for PTSD, including when delivered intensively (i.e., multiple sessions over 7 days). However, a substantial proportion of patients continue to meet criteria for PTSD or have residual PTSD symptoms post-treatment. Psilocybin-assisted CPT may be a potential solution, as preliminary evidence supports the potential of psilocybin to alleviate symptoms of PTSD.

Fifteen 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. Participants will complete clinician-administered scales, self-reported mental health questionnaires, and use a wearable device. After the 1-week interventional period, participants will enter a 12-weeks follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Venkat Bhat; Phone Number: 76404 416-360-4000; Email: venkat.bhat@utoronto.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • St. Michael's Hospital, Unity Health Toronto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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;
2. Have a Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score of 50 or higher, indicating moderate to severe PTSD symptoms;
3. Are willing to refrain from taking any psychiatric medications during the study period.

Exclusion Criteria:

1. Are pregnant or nursing, or are women of child bearing potential who are not practicing an effective means of birth control;
2. 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;
3. 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;
4. Have hypertension using the standard criteria of the American Heart Association (values of 140/90 or higher assessed on three separate occasions;
5. History of seizure disorder;
6. Uncontrolled insulin-dependent diabetes;
7. 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);
8. Have liver disease with the exception of asymptomatic subjects with Hepatitis C who have previously undergone evaluation and successful treatment;
9. Lifetime history of substance-induced psychosis;
10. Lifetime history of substance use disorder with a hallucinogen;
11. History of alcohol use disorder in the past 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Single dose of psilocybin 25mg Massed cognitive processing therapy	Drug: Psilocybin; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility and tolerability	Recruitment rate, withdrawal rate, adherence rate, data completion rate, percentage of participants with adverse events and responses to intervention based on qualitative data from the exit interview.	Up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score	The CAPS-5 is a semi-structured clinical interview used to assess index history of DSM-5-defined traumatic event exposure, including the most distressing event, time since exposure, and total number of exposures, as well as frequency and severity of posttraumatic stress symptoms.	Up to 13 weeks
Posttraumatic stress disorder Checklist-5 (PCL-5)	The PCL-5 is self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms, derived from the DSM-5 symptoms of PTSD.	Up to 13 weeks
Patient Health Questionnaire-9 (PHQ-9)	The PHQ-9 is a self-rated measure of depressive symptom severity in the past two weeks. Each of the nine items is rated on a Likert scale, ranging from 0 (not at all) to 3 (nearly every day), and summed for a total score between 0 (no symptoms) to 27 (most severe).	Up to 13 weeks
Generalized Anxiety Disorder Scale, 7-item (GAD-7)	Total score ranges from 0 to 21; a higher score denotes greater symptom severity.	Up to 13 weeks
Dissociative Experiences Scale II (DES-II)	The Dissociative Experiences Scale II is a 28-item, self-report measure of dissociative experiences.	Up to 13 weeks
Pittsburgh Sleep Quality Index (PSQI)	The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval.	Up to 13 weeks
World Health Organization Well-Being Index, 5-item (WHO-5)	The WHO-5 is a measure of overall well-being, rated on a scale of 0 to 25, with higher scores denoting higher quality of life.	Up to 13 weeks
Quality of relationships inventory (QRI)	The QRI is a self-report questionnaire used to determine the quality relationships consisting of 25 items that are evaluated on a 4-point Likert scale ranging from 1 = not true to 4 = almost always true.	Up to 13 weeks
Inventory of psychosocial functioning (IPF)	The IPF is an 80-item self-report instrument measuring PTSD-related functional impairment in the past 30 days.	Up to 13 weeks
Posttraumatic Maladaptive Beliefs Scale (PMBS)	The PMBS is a 15-item scale that was developed to measure maladaptive beliefs about life circumstances that may occur following trauma exposure.	Up to 13 weeks
Brief Experiential Avoidance Questionnaire (BEAQ)	The BEAQ is a 15-item self-report measure of experiential avoidance.	Up to 13 weeks
24-items Multidimensional Psychological Flexibility Inventory (MPFI-24)	The MPFI-24 is a 24-item self-report scale developed to assess the specific components of psychological flexibility and inflexibility.	Up to 13 weeks
Working Alliance Inventory- Short Form (WAI-SF)	The WAI-SF is a patient-rated measure of the alliance between a therapist and client.	Up to Day 7
Difficulties in Emotion Regulation Scale-Short Form (DERS-SF)	The DERS-SF is an 18-item measure used to identify emotional regulation issues in adults.	Up to 13 weeks
Self-Compassion Scale-Short Form (SCS-SF)	The SCS-SF is a 12-item self-report measure of self-compassion.	Up to 13 weeks
Psychological Insight Questionnaire (PIQ)	The PIQ is a 23-item self-report measure of acute experiences of insight (e.g. awareness into emotions, behaviors, beliefs, memories, or relationships) after taking a psychedelic.	Up to Day 3
Emotional Breakthrough Inventory (EBI)	The EBI is a measure of emotional release/breakthrough experienced during the acute psychedelic state.	Up to Day 3
Altered States of Consciousness Rating Scale (ASC)	The ASC measures altered states of consciousness.	Up to Day 3
Acceptance/Avoidance-Promoting Experiences Questionnaire (APEQ)	The APEQ is a psychometric self-report tool for measuring aspects of the acute psychedelic experience that are associated with longer-term changes in psychological flexibility.	Up to Day 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on digital physiological passive data collected through the use of a wearable device	Example: sleep, activity	Up to 16 weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: University of Ottawa; Toronto Metropolitan University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cognitive Processing Therapy; Psilocybin; Post Traumatic Stress Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: 23-230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No