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

NCT05876481 | Unknown Phase 2 FDA Drug

• 1 other identifier: CS-2023-002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PTSD

Keywords

PTSD; Veteran; Psilocybin-assisted Psychotherapy; Feasibility trial

Outcome Measures

Primary Outcomes (1)

• Symptoms of PTSD measured using the Posttraumatic Stress Disorder Checklist For DSM-5 (PCL- PTSD symptoms

  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 Outcomes (8)

• Core features of PTSD and complex PTSD measured using the International Trauma Questionnaire (ITQ)

  Change from baseline ITQ score at one month follow up

• Difficulties with anger measured using the Dimensions of Anger Reactions (DAR-5)

  Change from baseline DAR-5 score at one month follow up

• Depression symptoms measured using the Patient Health Questionnaire (PHQ-9)

  Change from baseline PHQ-9 score at one month follow up

• General anxiety symptoms measured using the Generalised Anxiety Disorder (GAD-7)

  Change from baseline GAD-7 score at one month follow up

• Mental wellbeing measured using the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS)

  Change from baseline SWEMWBS score at one month follow up

Other Outcomes (9)

• Semi-structured qualitative interviews

  Consenting participants will be contacted at one-month follow up.

• Adverse Experiences in Psychotherapy

  Treatment end (at CPT session 12), week 8

• Retention rate

  Study end (approximately 2 years)

Study Arms (1)

Psilocybin-assisted Psychotherapy

EXPERIMENTAL

All participants will receive 25mg psilocybin (capsule, hard, oral administration) in two 8-hour psilocybin dosing sessions, followed by Cognitive Processing Therapy.

Drug: Psilocybin

Interventions

Psilocybin DRUG

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

Psilocybin-assisted Psychotherapy

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• History of poor cooperation or unreliability
• Engaged in compensation litigation whereby financial game would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders
• Any other current problems that may interfere with participation (e.g., availability, private space for sessions at home)
• Has hearing impairment that could interfere with ability to participate in the study
• Is unable to provide written informed consent
• Has known hypersensitivity or previous allergic reaction to any constituent of psilocybin
• Pregnant or breastfeeding
• BMI \<18 or \>35 or non-consent for metric to be measured during assessment visit
• 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
• 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.
• 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)
• May present serious risk to others (established via clinical interview and contact with treating psychiatrist)
• Is likely to be re-exposed to index trauma or other significant trauma, lack social support, or lack of stable living situation
• History of myocardial infarction, angina, cerebrovascular accident, aneurysm, or pulmonary vascular disease
• Has had Transient Ischemic Attack (TIA) within past 6 months

Sponsors & Collaborators

• Combat Stress: lead
• The Watson Trust: collaborator

Study Sites (1)

Combat Stress

Leatherhead, Surrey, KT22 0BX, United Kingdom

Location

Related Publications (8)

• Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJ. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021 Apr 15;384(15):1402-1411. doi: 10.1056/NEJMoa2032994.

  PMID: 33852780 BACKGROUND

• Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.

  PMID: 33146667 BACKGROUND

• Dos Santos RG, Hallak JEC. Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms. Neurosci Biobehav Rev. 2020 Jan;108:423-434. doi: 10.1016/j.neubiorev.2019.12.001. Epub 2019 Dec 3.

  PMID: 31809772 BACKGROUND

• Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.

  PMID: 26841800 BACKGROUND

• Cloitre M, Stolbach BC, Herman JL, van der Kolk B, Pynoos R, Wang J, Petkova E. A developmental approach to complex PTSD: childhood and adult cumulative trauma as predictors of symptom complexity. J Trauma Stress. 2009 Oct;22(5):399-408. doi: 10.1002/jts.20444. Epub 2009 Sep 30.

  PMID: 19795402 BACKGROUND

• Morina N, Wicherts JM, Lobbrecht J, Priebe S. Remission from post-traumatic stress disorder in adults: a systematic review and meta-analysis of long term outcome studies. Clin Psychol Rev. 2014 Apr;34(3):249-55. doi: 10.1016/j.cpr.2014.03.002. Epub 2014 Mar 14.

  PMID: 24681171 BACKGROUND

• Kitchiner NJ, Roberts NP, Wilcox D, Bisson JI. Systematic review and meta-analyses of psychosocial interventions for veterans of the military. Eur J Psychotraumatol. 2012;3. doi: 10.3402/ejpt.v3i0.19267. Epub 2012 Dec 5.

  PMID: 23233869 BACKGROUND

• Straud CL, Siev J, Messer S, Zalta AK. Examining military population and trauma type as moderators of treatment outcome for first-line psychotherapies for PTSD: A meta-analysis. J Anxiety Disord. 2019 Oct;67:102133. doi: 10.1016/j.janxdis.2019.102133. Epub 2019 Aug 18.

  PMID: 31472332 BACKGROUND

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

Study Officials

• Prof. Dominic Murphy

  Combat Stress

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prof. Dominic Murphy

CONTACT

01372 587 017; dominic.murphy@combatstress.org.uk

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 4, 2023
• First Posted: May 25, 2023
• Study Start: June 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: August 1, 2025
• Last Updated: May 25, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)