Evaluation of Psilocybin-assisted Psychotherapy (PaP) for the Treatment of Post-traumatic Stress Disorder (PTSD) in Military Veterans

May 16, 2023 updated by: Combat Stress

Evaluation of the Acceptability, Safety, Feasibility, and Efficacy of Psilocybin-assisted Psychotherapy (PaP) for the Treatment of Post-traumatic Stress Disorder (PTSD) in Military Veterans

Post-Traumatic Stress Disorder (PTSD) is a mental health condition that occurs as a result of a traumatic experience. Symptoms include feeling anxious, flashbacks, nightmares and difficulty sleeping. Several studies indicate that psilocybin-assisted psychotherapy (PaP) may be an effective treatment for a number of mental health conditions. This has led to PaP being designated as a "breakthrough treatment" by the FDA in the US. Despite indications that PaP may hold benefits in treating individuals with posttraumatic stress disorder (PTSD), this remains to be investigated. As such, the present study aims to examine the acceptability, feasibility, safety, and efficacy of PaP (psilocybin administered with psychotherapy) in treating PTSD in military veterans.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Recent studies have shown that Psilocybin-Assisted Psychotherapy (PaP) for individuals with treatment-resistant depression can result in outcomes that exceed routine psychotherapy. Psilocybin may have a catalytic effect on the psychotherapeutic process, enhancing introspection and interoception. PaP may similarly benefit the treatment of posttraumatic stress disorder (PTSD). Research indicates high treatment drop-out rates (approximately 30%) among PTSD patients, and moderate remission rates (approximately 44%) 40 months after completing treatment. Furthermore, some veterans with PTSD have poorer treatment responses than members of the general public. This suggests that alternative treatment approaches may be required to support veterans who do not benefit from standard evidence-based approaches. This study aims to explore the acceptability, feasibility, safety and efficacy of PaP for veterans with PTSD. A total of eight military veterans will be recruited. The study involves two non-directive preparatory sessions, two dosing sessions of psilocybin, followed by 12 sessions of Cognitive Processing Therapy. It is hypothesised that PaP will result in a significant reduction in PTSD symptoms, as indicated by PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM-5; PCL-5) scores from baseline to one-month follow-up.

Study Type

Interventional

Enrollment (Estimated)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Surrey
      • Leatherhead, Surrey, United Kingdom, KT22 0BX
        • Combat Stress

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged 18-65 years
  2. Fluent in English (reading and speaking)
  3. Has internet access via computer or tablet
  4. Is able to commit to the study visits and treatment length
  5. Can provide a contact (relative, close friend, other support person) who is able to accompany the participant to dosing visits
  6. Agrees to inform researchers within 48 hours of any medical treatments or procedures
  7. Can swallow pills
  8. Agrees to lifestyle restrictions: not to consume alcohol within 24 hours prior to dosing, and to not consume more caffeine than usual
  9. Agrees to not participate in any other clinical trials for the duration of the study
  10. PCL-5 score ≥33
  11. At least one unsuccessful evidence-based psychotherapy/pharmacotherapy for PTSD

Exclusion Criteria:

General exclusion criteria:

  1. History of poor cooperation or unreliability
  2. Engaged in compensation litigation whereby financial game would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders
  3. Any other current problems that may interfere with participation (e.g., availability, private space for sessions at home)
  4. Has hearing impairment that could interfere with ability to participate in the study
  5. Is unable to provide written informed consent
  6. Has known hypersensitivity or previous allergic reaction to any constituent of psilocybin
  7. Pregnant or breastfeeding
  8. BMI <18 or >35 or non-consent for metric to be measured during assessment visit
  9. Has been diagnosed with, or has first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to medical condition), or bipolar I disorder
  10. Current alcohol or substance use disorder (other than caffeine or nicotine) requiring detox, or currently in withdrawal from such disorder. Exception for milder disorder if realistic plan (agreed by researcher, therapy team, and medical monitor) for successfully mitigating alcohol/substance use to prevent use from impacting participation, safety, and/or efficacy of the treatment.

    Mental health exclusion:

  11. Schizophrenia spectrum or other psychotic disorders or first degree relative with such disorders (incl. major depressive disorder with psychotic features, or Bipolar I or II disorders)
  12. May present serious risk to others (established via clinical interview and contact with treating psychiatrist)
  13. Is likely to be re-exposed to index trauma or other significant trauma, lack social support, or lack of stable living situation

    Physical health exclusion:

  14. History of myocardial infarction, angina, cerebrovascular accident, aneurysm, or pulmonary vascular disease
  15. Has had Transient Ischemic Attack (TIA) within past 6 months
  16. Has uncontrolled hypertension (140/90 mmHG or higher assessed on three separate occasions). Adequately controlled hypertension does not exclude participant
  17. Has Wolff-Parkinson-White syndrome or other accessory pathway conditions that have not been successfully eliminated by ablation
  18. History of arrhythmia, other than premature atrial contractions (PACs) or occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease, within past 12 month
  19. History of risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, Long QT Syndrome family history)
  20. Requires use of concomitant medications that may prolong the QT/QTc interval during psilocybin dosing sessions
  21. Marked Baseline prolongation of QT/corrected QT interval (QTc; e.g., repeated demonstration of a QTc interval >450ms and >460ms in females corrected by Bazett's formula). For transgender or non-binary subjects, QTc interval will be evaluated based on sex assigned at birth, unless the subject has been on hormonal treatment for five or more years.
  22. History of medical condition that could make receiving a sympathomimetic drug harmful because of increased blood pressure and heart rate
  23. Haptic enzymes alkaline phosphatase (ALP), alanine transaminase (ALT), Aspartate aminotransferase (AST) or Gamma-glutamyl Transferase (GGT) > three times upper limit of normal (ULN), or total bilirubin levels >2x ULN
  24. Previous indication of liver or kidney damage
  25. Current Hepatitis C virus (HCV) infection - Asymptomatic HCV permitted if previously undergone evaluation and treatment as needed
  26. Current uncontrolled Type 2 diabetes mellitus
  27. Current uncontrolled hypothyroidism
  28. Current or historic glaucoma unless participation approved by an ophthalmologist
  29. History of traumatic brain injury (TBI)/cognitive impairment limiting ability to engage in treatment (e.g., memory or concentration problems, impulsivity related to brain injury)
  30. Current neurological illness including, but not limited to, seizure disorders, frequent migraines (or on prophylaxis for same), multiple sclerosis, movement disorders, history of significant head trauma, or central nervous system (CNS) tumour)
  31. The presence of other severe acute or chronic medical condition, psychiatric condition or laboratory abnormality that may increase the risk associated with participation or may interfere with interpretation of trial results. Please note: mild, stable chronic medical problems (e.g., Type 1 or 2 Diabetes Mellitus, HIV infection, glaucoma, hypothyroidism, hepatitis C, hepatic or renal disease, etc.) may be enrolled if Investigator and research psychiatrist agree that condition(s) would not: significantly increase risk of psilocybin administration, or be likely to produce significant symptoms during the study that could interfere with participation, or be confused with side effects of Investigational Product
  32. Previous use of psilocybin or other psychedelic substance (except cannabis) on more than 5 occasions and/or use of the same within the past 5 years
  33. Previous use of psilocybin, methylenedioxymethamphetamine (MDMA), ketamine (or substances reportedly containing psilocybin, MDMA, or ketamine) with therapeutic aim for current PTSD diagnosis
  34. Has received Electroconvulsive Therapy (ECT) within 12 weeks of enrolment
  35. Requires ongoing concomitant therapy with a psychiatric medication (unless deemed acceptable by the research psychiatrist)
  36. Exposure to other investigational drug/device within 30 days of enrolment

    Medication exclusion criteria:

  37. Over-the-counter products intended to affect mood/anxiety
  38. Efavirenz
  39. Lithium
  40. "Rest-Category" Antidepressants (e.g., mirtazapine, trazodone, bupropion); Exception if ≤7.5mg mirtazapine, or ≤50mg trazodone as sleeping medication
  41. Antipsychotics/Neuroleptics; Exception if ≤50mg quetiapine as sleeping medication
  42. Stimulants
  43. The following medications are permitted if the dose is hypnotic: selective serotonin reuptake inhibitor (SSRIs); Tricyclic antidepressants (TCAs); monoamine oxidase inhibitor (MAOIs)
  44. The following medications are permitted if their use is unaltered during the study: Benzodiazepines "Z-drugs" (e.g., zolpidem); Anticonvulsants; Antihistamines
  45. Medications which are permitted as determined case-by-case by research psychiatrist: non-psychiatric, but mind-altering medication (e.g., morphine, dexamethasone, etc.).
  46. Not to be used 72hrs prior to psilocybin dosing session: Sildenafil (Viagra), tadalafil, or similar medications
  47. Not to be used on dosing days and research psychiatrist discretion: Medical cannabis

    Risk exclusion criteria:

  48. Current suicidal ideation/intent/action
  49. Previous (within previous 6 months) suicidal ideation/intent/action
  50. Current and previous deliberate self-harm

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Psilocybin-assisted Psychotherapy
All participants will receive 25mg psilocybin (capsule, hard, oral administration) in two 8-hour psilocybin dosing sessions, followed by Cognitive Processing Therapy.
Product name: Psilocybin Pharmaceutical form: capsule, hard Dose number and units: 25 mg per day (8-hour dosing session) x 2 Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptoms of PTSD measured using the Posttraumatic Stress Disorder Checklist For DSM-5 (PCL- PTSD symptoms
Time Frame: Change from baseline PCL-5 score at one month follow up
Symptoms of PTSD measured using the Posttraumatic Stress Disorder Checklist For DSM-5 (PCL- 5). Scores range from 0-80, with a higher score indicated a worse outcome.
Change from baseline PCL-5 score at one month follow up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Core features of PTSD and complex PTSD measured using the International Trauma Questionnaire (ITQ)
Time Frame: Change from baseline ITQ score at one month follow up
Scores range from 0 to 48 with a higher score indicating a worse outcome.
Change from baseline ITQ score at one month follow up
Difficulties with anger measured using the Dimensions of Anger Reactions (DAR-5)
Time Frame: Change from baseline DAR-5 score at one month follow up
Scores range from 5-25, with a higher score indicating a worse outcome.
Change from baseline DAR-5 score at one month follow up
Depression symptoms measured using the Patient Health Questionnaire (PHQ-9)
Time Frame: Change from baseline PHQ-9 score at one month follow up
Scores range from 0-27, with a higher score indicating a worse outcome.
Change from baseline PHQ-9 score at one month follow up
General anxiety symptoms measured using the Generalised Anxiety Disorder (GAD-7)
Time Frame: Change from baseline GAD-7 score at one month follow up
Scores range from 0-14, with a higher score indicating a worse outcome.
Change from baseline GAD-7 score at one month follow up
Mental wellbeing measured using the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS)
Time Frame: Change from baseline SWEMWBS score at one month follow up
Scores range from 7-35, with a lower score indicating a worse outcome.
Change from baseline SWEMWBS score at one month follow up
Perceived social support measured using the Oslo Social Support Scale
Time Frame: Change from baseline OSS score at one month follow up
Scores range from 3-14, with a higher score indicating a worse outcome.
Change from baseline OSS score at one month follow up
Challenging aspects of experiences with psilocybin measured using the Challenging Experience Questionnaire
Time Frame: Administered at the end of dosing session one, week 4
Scores range from 5-25, with a higher score indicating a worse outcome.
Administered at the end of dosing session one, week 4
Challenging aspects of experiences with psilocybin measured using the Challenging Experience Questionnaire
Time Frame: Administered at the end of dosing session two, week 5
Measures a phenomenological profile of experiences with scores not indicative of more or less strongly challenging experiences.
Administered at the end of dosing session two, week 5

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Semi-structured qualitative interviews
Time Frame: Consenting participants will be contacted at one-month follow up.
Intervention acceptability and experiences of the study will be measured using semi-structured qualitative interviews
Consenting participants will be contacted at one-month follow up.
Adverse Experiences in Psychotherapy
Time Frame: Treatment end (at CPT session 12), week 8
Experiences that may occur in therapy measured using the Adverse Experiences in Psychotherapy to assess feasibility
Treatment end (at CPT session 12), week 8
Retention rate
Time Frame: Study end (approximately 2 years)
Feasibility endpoint
Study end (approximately 2 years)
Did Not Attend (DNA) rate
Time Frame: Study end (approximately 2 years)
Feasibility endpoint
Study end (approximately 2 years)
Recruitment of target sample size (n = 8)
Time Frame: Study end (approximately 2 years)
Feasibility endpoint
Study end (approximately 2 years)
Incidence of adverse events across the duration of the study
Time Frame: Study end (approximately 2 years)
Safety endpoint, calculated as total number of adverse events reported across the study. Adverse events as defined in the study protocol.
Study end (approximately 2 years)
Hazardous and harmful alcohol use measured using the Alcohol Use Disorder Identification Test
Time Frame: Baseline
Background measure. Scores range from 0-40, with a higher score indicating a worse outcome.
Baseline
Possible drug-related problems measured using the Drug Use Disorders Identification Test
Time Frame: Baseline
Background measure. Scores range from 0-44, with a higher score indicating a worse outcome.
Baseline
Difficulties with moral injury in relation to a potentially morally injurious event measured using the Moral Injury Outcome Scale (MIOS)
Time Frame: Baseline
Background measure. Scores range from 0-56, with a higher score indicating a worse outcome.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: Prof. Dominic Murphy, Combat Stress

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2023

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

August 1, 2025

Study Registration Dates

First Submitted

April 4, 2023

First Submitted That Met QC Criteria

May 16, 2023

First Posted (Actual)

May 25, 2023

Study Record Updates

Last Update Posted (Actual)

May 25, 2023

Last Update Submitted That Met QC Criteria

May 16, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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