Psilocybin-Assisted Psychotherapy for Posttraumatic Stress Disorder in Military Veterans: A Pilot Feasibility Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ARQ National Psychotrauma Centrum

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-06-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Landelijk Zorgsysteem voor Veteranen (LZV) · Filament Health

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Others, Safety

The primary objective of this study is to evaluate the feasibility, safety, and effect of psilocybin-assisted psychotherapy for veterans with treatment-refractory PTSD.

Secondary objectives 2

1. Evaluate the effect of psilocybin-assisted psychotherapy for PTSD on functional impairment.
2. Evaluate the effect of psilocybin-assisted psychotherapy on depressive symptoms.

Conditions and MedDRA coding

Posttraumatic stress disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participants are between 18 and 70 years old at the time of signing the informed consent.
2. At Screening, meet DSM-5 criteria for current PTSD with a symptom duration of at least 6 months.
3. At Screening, have a PCL-5 score of 40 or greater (i.e., moderate to severe PTSD).
4. At Screening, meet the definition of treatment-refractory PTSD, defined as having had at least two evidence-based treatments, of which at least one was a trauma-focused psychotherapy consisting of at least 8 treatment sessions.
5. Is a veteran of the Dutch Armed Forces.

Exclusion criteria 11

1. Have current cluster A- or B personality disorders.
2. Have a history of, or a current primary psychotic disorder, bipolar disorder type 1, or major depressive disorder with psychotic features.
3. Has a first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I disorder.
4. Have current anorexia nervosa or bulimia nervosa.
5. Have current dissociative identity disorder.
6. Have a current: a) Severe alcohol or cannabis use disorder (meets at least 6 of 11 diagnostic criteria per DSM-5) within the 12 months prior to enrollment; b) Moderate alcohol or cannabis use disorder (4 or 5 of 11 diagnostic criteria per DSM-5) within the 12 months prior to enrollment, unless in early remission (i.e., at least 3 months without symptoms, with the exceptions of possible craving/urge to use); Mild alcohol or cannabis use disorder is not an exclusion criterion (2 or 3 of 11 diagnostic criteria per DSM-5).
7. Have an illicit drug (other than cannabis) or prescription drug substance use disorder at any severity within 12 months prior to enrollment.
8. Any participant presenting current serious suicide risk, as determined through screening interview, responses to C-SSRS, and clinical judgment will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior will not be enrolled. Any participant presenting with the following on the baseline/screening C-SSRS will be excluded: a) Suicidal ideation score of 4 or greater within the last month of the assessment at a frequency of once a week or more. b) Suicidal ideation score of 5 within the last 6 months of the assessment. c) Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Participants with non-suicidal self-injurious behavior may be included if approved by the study physician.
9. Have a current history of one of the following cardiovascular conditions: a) coronary artery disease, congenital long QT syndrome (prior diagnosis), cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction (prior diagnosis); b) tachycardia (defined as heart rate > 100 beats per minute); c) clinically significant Screening ECG abnormality (including, but not limited to, atrial fibrillation, Wolff-Parkinson-White syndrome, ventricular tachycardia), Note: A QTcF interval > 450 milliseconds is considered a clinically significant ECG abnormality; d) artificial heart valve; e) additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome); f) any other significant current or history of cardiovascular condition, based on the clinical judgment of the study physician, that would make a participant unsuitable for the study.
10. Have uncontrolled severe hypertension, defined as confirmed (repeat office and/or out-of-office) blood pressure consistent with grade 2–3 hypertension (office systolic ≥160 mmHg and/or diastolic ≥100 mmHg), or grade 1 hypertension in combination with other cardiovascular risk factors, resulting in an increased cardiovascular risk profile according to the 2023 European Society of Hypertension (ESH) guideline risk stratification. Blood pressure status may be confirmed by repeated clinic measurements or home/ambulatory blood pressure monitoring if clinically indicated. Participants with well-controlled hypertension that has been successfully treated with anti-hypertensive medicines may be enrolled.
11. Have a history of any medical condition that could make receiving a psilocybin harmful because of temporary increases in blood pressure and heart rate. This includes, but is not limited to cerebrovascular accident, heart failure, or unstable insulin-dependent diabetes.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Number, percentage and reasons of screen failures and drop-out
2. Descriptive statistics of the scores on the Treatment Acceptability/Adherence Scale (TAAS-M), measured post-treatment (Visit 16)
3. Qualitative analysis of semi-structured interviews conducted with participants post-treatment (Visit 16)
4. Mean change in CAPS-5-R Total Severity Score from Baseline (Visit 4) to 13 weeks post Baseline (Visit 15).
5. Severity, incidence and frequency of adverse events (AEs), serious adverse events (SAEs), suicidal ideation and behavior, concomitant medication use, and vital signs throughout the study
6. Descriptive statistics of changes in Columbia Suicide Severity Rating Scale (C-SSRS) scores
7. Descriptive statistics of concomitant medication use
8. Mean changes in blood pressure, heart rate, and body temperature from pre-psilocybin administration to end of each Psilocybin Session

Secondary endpoints 2

1. Mean change in Sheehan Disability Scale Total Severity Score from Baseline (Visit 4) to 13 weeks post Baseline (Visit 15).
2. Mean change in Beck's Depression Inventory-II Total Severity Score from Baseline (Visit 4) to 13 weeks post Baseline (Visit 15)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ARQ National Psychotrauma Centrum

Sponsor organisation

ARQ National Psychotrauma Centrum

Address

Nienoord 5

City

Diemen

Postcode

1112 XE

Country

Netherlands

Scientific contact point

Organisation

ARQ National Psychotrauma Centrum

Contact name

Tijmen Bostoen

Public contact point

Organisation

ARQ National Psychotrauma Centrum

Contact name

Tijmen Bostoen

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications