Recruiting

Phase 1

MDMA & PsilocybinPsilocybin and Methylenedioxymethamphetamine (MDMA) for Post-traumatic Stress Disorder (PTSD)

Sponsor:

Johns Hopkins University

Code:

NCT06989957

Conditions

Posttraumatic Stress Disorder

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Not accepted

Interventions

Psilocybin

MDMA

Study Details

Brief summary:

The purpose of this study is to assess the safety and effectiveness of co-administered MDMA and psilocybin in military Veterans with a diagnosis of Posttraumatic Stress Disorder (PTSD).

To apply or learn more, please view our website: https://hopkinspsychedelic.org/pamvet

Conditions

Posttraumatic Stress Disorder

Study ID

NCT06989957

Start date

Sep 17, 2025

Status verified date

Sep, 2026

Completion date

Aug, 2029

Anticipated

Primary completion date

Aug, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Not accepted

Inclusion Criteria:

>=21 years old
Military Veteran
Have given written informed consent
Able to swallow pills
Have a confirmed DSM-5 diagnosis of Post-traumatic Stress Disorder with symptom duration >= 6 months
Have a baseline CAPS-5 score of >=28
Be judged by study team clinicians to be at low acute risk for suicidality
Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study.
Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
Agree to refrain from using any psychoactive drugs, including alcoholic beverages within 24 hours of each drug administration. The exceptions are caffeine and nicotine.
Agree to refrain from using any caffeine or nicotine within 2 hours of dosing session start.
Agree not to take any as needed (PRN) medications on the mornings of drug sessions without approval of the treatment team.
Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
Agree to stop taking 5HT2A antagonist medications at least 5 half-lives before dosing.
Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
Have no lifetime use of serotonin 2A receptor (5-HT2A) agonist hallucinogens and/or MDMA at a greater dosage than a level typically defined as 'microdose.'
Have at least a high school level of education or equivalent (e.g. GED).
Weigh between 40kg- 120kg.
Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable
Agree to be released into the custody of a close friend or family member who has agreed to take charge of the study participant as a condition of leaving the testing facility, or agree to be accompanied home or to an accommodation by a member of the study team
May have a history of or current Diabetes Mellitus (Type 2) if additional screening measures rule out underlying cardiovascular disease, if the condition is judged to be stable on effective management, and with approval by the Medical Monitor
May have hypothyroidism if taking adequate and stable thyroid replacement medication
May have a history of, or current, glaucoma if approval for study participation is received from an ophthalmologist

Exclusion Criteria:

Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder
Current or history within one year of meeting DSM-5 criteria for a moderate or severe alcohol, or other drug use disorder (excluding tobacco, caffeine, and cannabis)
Current or history within one year of meeting DSM-5 criteria for Borderline Personality Disorder.
Clinically significant suicidal ideation (e.g. with strong intent or means; C-SSRS > 3) within past 6 months
Have a first degree relative with schizophrenia or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I disorder
Nicotine dependence that would be incompatible with an individual to be nicotine free for 8-10 hours on a dosing session day
Medical condition incompatible with MDMA or psilocybin administration (e.g., cardiovascular, drug-induced hyperthermia, hyponatremia).
Currently taking on a daily basis any medications (including herbal substances and supplements) with a Central Nervous System effect on serotonin (including serotonin-reuptake inhibitors (SRIs), monoamine oxidase inhibitors (MAOIs)), or any medications that affect liver enzyme (2D6) metabolism (e.g., Bupropion)
Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, uridine diphosphate glucuronosyltransferase enzyme (UGT1A9) inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag.
On unstable/changing dose of opioid, benzodiazepine or other psychoactive or pain medication within 4 weeks prior to enrollment and/or unable to abstain from medication on drug administration day
Current use/positive toxicology for illicit drugs; or positive breath alcohol test at screening and/or prior to each drug administration session
Lifetime use of any psychedelic drug (e.g., MDMA, psilocybin) at a dosage greater than a level typically defined as 'microdose.'
Clinically significant transaminitis (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than two times normal value).
Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing;
Women who are of child-bearing potential and sexually active agree to use highly effective means of birth control (i.e. implants, injectables, combined oral contraceptives, progestin-containing intrauterine device (IUD) or vasectomised partner) for the duration of this study.
Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged corrected QT interval (QTc) (i.e., QTc > 450 msec), heart valve, or transient ischemic attack (TIA) in the past year.
History of seizures and/or epilepsy with history of seizures.
Type 1 diabetes.
BMI < 18
Are likely, in the investigator's opinion and via observation during the Preparatory Period, to be re-exposed to the index trauma or other significant trauma in daily life, lack social support, or lack a stable living situation.
Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment
Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, or aneurysm.

Participants with other mild, stable chronic medical problems may be enrolled if the site physician and investigators agree the condition would not significantly increase the risk of MDMA administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the study drugs. Examples of stable medical conditions that could be allowed include, but are not limited to Diabetes Mellitus (Type 2), Human Immunodeficiency Virus (HIV) infection, Gastroesophageal Reflux Disease (GERD), etc.
Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism would require exclusion
Have symptomatic liver disease or significant liver enzyme elevations

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Experimental MDMA + psilocybin (exact dosage not disclosed)

MDMA will be given initially, followed by psilocybin 30 minutes later.

active comparator: Comparator MDMA + psilocybin (exact dosage not disclosed)

MDMA will be given initially, followed by psilocybin 30 minutes later.

Interventions

Psilocybin

Experimental Psilocybin (exact dosages not disclosed)

Psilocybin

Comparator Psilocybin (exact dosages not disclosed)

MDMA

Experimental MDMA (exact dosages not disclosed)

MDMA

Comparator MDMA (exact dosages not disclosed)

Primary outcome measure

Incidence of Adverse Events [ Time Frame: 30 weeks ]
The Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 33 weeks ]
Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual-5 (CAPS-5) [ Time Frame: 33 weeks ]
PTSD Checklist (PCL-5) [ Time Frame: 33 weeks ]
World Health Organization Quality of Life- Brief version (WHOQOL-BREF) [ Time Frame: 33 weeks ]

Central Contacts and Locations

Central contacts

Chloe Ford, MSc

410-550-0237 cford36@jh.edu

Locations

Johns Hopkins Center for Psychedelic and Consciousness Research

Recruiting

Baltimore, Maryland, United States, 21224

Contacts

Chloe Ford, MSc

410-550-0237 cford36@jh.edu

Principal Investigator:

Brandon Weiss, PhD

More Information

Sponsor

Johns Hopkins University

Last update posted

Sep 4, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-09-04.