Clinical Trial of MDMA-Assisted Therapy for Military Service Members With Posttraumatic Stress Disorder

Starting soon · Phase 2

Conditions studied: PTSD, Post Traumatic Stress Disorder PTSD, Post Traumatic Stress Disorder

In brief

This study is a Phase 2, randomized, double-blind, active-controlled, two-arm, single-site clinical trial designed to evaluate the safety, tolerability, and feasibility of MDMA-Assisted Therapy (MDMA-AT) for Service Members (Active Duty, Guard, or Reserve) diagnosed with moderate-to-severe Post-Traumatic Stress Disorder (PTSD) within a Military Health System (MHS) setting. The trial incorporates Acceptance and Commitment Therapy (ACT) as a core therapeutic modality. Participants will receive MDMA-AT utilizing either full-dose or active-control low-dose MDMA. The trial will also assess a regional referral center model by recruiting participants locally from the National Capital Region and non-locally across the MHS.

Key facts

Study ID

NCT07704762

Run by

U.S. Army Medical Research and Development Command

People needed

86

Starts

2026-10-01

Expected to finish

2028-10-01

Last updated by the study team

2026-07-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Positive endorsement of at least 1 index trauma on the LEC-5.
• Have a PCL-5 total score of 38 or greater at screening.
• Meet DSM-5-TR criteria for current PTSD per Mini International Neuropsychiatric Interview (MINI) at screening with a symptom duration of 6 months or longer.
• Meet criteria for PTSD diagnosis per CAPS-5-R with a score of 26 or greater.
• Are at least 18 years old at the time of enrollment.
• Weigh greater than 48 kilograms.
• Are able to swallow pills.
• Are fluent in speaking, reading, and comprehending English.
• Must agree to inform the investigators within 48 hours of any new medications, medical conditions, and procedures.
• Females of childbearing potential must have a negative pregnancy test at study entry and prior to each Dosing Session and must agree to use adequate birth control for the duration of the study until at least 30 days after the final dosing session. Adequate birth control methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e. condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Non-childbearing potential is defined as permanent sterilization, postmenopausal, or assigned male at birth.
• Males must agree to use adequate birth control for the duration of the study until at least 30 days after the final dosing session. Adequate birth control methods for males include double barrier contraception (condom with spermicidal gel or foam), surgical sterility (defined as a vasectomy at least 3 months prior to the screening visit), or abstinence.
• Must agree to refrain from sperm, egg, blood, and bone marrow donations for at least 30 days after the final dosing session.
• Must have a 12-lead electrocardiogram (EKG) with QTc < 450 ms and no clinically significant abnormalities, as determined by a cardiologist.
• Are able to demonstrate comprehension of consent form and study instructions, and provide informed consent.
• Agree to have study visits recorded, including Dosing Sessions, Independent Rater assessments, and non-drug therapy sessions.
• Must provide an emergency contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event a participant is imminently unsafe or unreachable.
• Agree to the following lifestyle modifications (described in more detail in the Informed Consent Form): comply with requirements for fasting and refraining from certain medications prior to Dosing Sessions; not participate in any other interventional clinical trials during the duration of this study without prior approval of the Independent Safety Monitor; remain overnight at the study site or have an identified support person that can remain with the participant and escort them to the therapy session the day after each dosing; and commit to medication dosing, therapy, and study procedures.
• Must be Active Duty, National Guard, or Reserve in the United States military.
• Must receive approval from their command to participate in the study.
• Must be DEERS eligible.

You may not qualify if…

• History of or current primary psychotic disorder to include Schizophrenia, Schizoaffective Disorder, or Bipolar Disorder 1 assessed via MINI or clinical evaluation.
• Current Major Depressive Disorder with Psychotic Features assessed via MINI or clinical evaluation.
• Current eating disorder with active purging assessed via MINI or clinical evaluation.
• Current Borderline Personality Disorder assessed via SCID-5-PD or clinical evaluation.
• Any of the following findings on Screening C-SSRS:
• Suicidal ideation score of 5 within the last month
• Suicidal ideation score of 4 or greater in the last month at a frequency of once per week or more
• Any suicidal behaviors within the last 3 months. The exception is that non suicidal self-injurious behavior is not exclusionary if approved by the PI.
• Current high suicide risk or is likely to require psychiatric hospitalization, as determined through C-SSRS, clinical interview, or clinical judgment of the investigator. Distant history of suicide attempts without current high suicide risk factors is not exclusionary.
• Current severe substance use disorder (6 or more criteria per MINI) not in sustained remission (criteria not met for past 12 months) at time of enrollment. I.e., severe substance use disorders may only be included if in sustained remission. Tobacco/nicotine use disorders may be included regardless of severity.
• Current moderate substance use disorder (4-5 criteria per MINI) not in early remission (criteria not met for past 3-12 months) or sustained remission (criteria not met for past 12 months) at time of enrollment. I.e., moderate substance use disorders may only be included if in early or sustained remission (criteria not met for 3 or more months). Tobacco/nicotine use disorders may be included.
• For any illicit or prescribed substance: current substance use disorder of any severity, not in sustained remission (criteria not met for past 12 months). I.e., substance use disorders of any severity with illicit or prescribed substances may only be included if in sustained remission.
• Any urine drug testing during screening or enrollment that is confirmed positive for a non-prescribed substance, and the result cannot be better explained as a false positive due to another concomitant prescribed medication or proven dietary practice.
• Have current or history of psychiatric diagnoses or symptoms that may negatively affect study participation.
• Clinically significant abnormalities on screening 12-lead EKG or 1 minute 12-lead rhythm strip that precludes administration of MDMA, stimulants, or sympathomimetics, as determined by a cardiologist.
• Two or more premature ventricular contractions (PVCs) on 1-minute rhythm strip. 1 minute 12-lead rhythm strip will be obtained when there are one or more PVCs on screening EKG or when indicated by a cardiologist.
• Resting QTc ≥ 450 ms.
• History of drug-induced QTc prolongation.
• Inability to hold or discontinue concomitant medications that significantly prolong the QTc interval.
• Clinically significant cardiac or cardiovascular abnormalities, including history of myocardial infarction, unexplained exertional syncope, Torsade de Pointes, congenital long QT syndrome, hypertrophic cardiomyopathy, congestive heart failure, family history of Long QT Syndrome, persistent atrial fibrillation, symptomatic valvular heart disease, asymptomatic severe aortic stenosis, asymptomatic severe mitral stenosis, history of diagnosis of aortic dissection or asymptomatic aortic aneurysm > 4.5 cm at the sinus of Valsalva, or history of untreated angina pectoris or unrevascularized coronary stenosis > 70%.
• Current clinically significant electrolyte abnormalities, to include hyponatremia and hypokalemia.
• Has clinically significant abnormal laboratory results during screening that indicate impaired liver function, to include ALT or AST >2x ULN or Total bilirubin >1.5 mg/dL unless history of Gilbert's Syndrome
• Renal disease defined as eGFR <45 mL/min/1.73m² or creatinine >2.0 mg/dL, end-stage kidney disease, dialysis, history of renal transplant, clinically significant or progressive renal disease deemed to increase risk, or recent/unstable renal function consistent with acute kidney injury at screening. Participants with eGFR 45-59 mL/min/1.73m² may be eligible only if renal function is stable and cleared by the study physician.
• Uncontrolled essential hypertension defined as blood pressures of greater than 140/90 mmHg assessed on three separate occasions. May have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if additional screening is passed to rule out underlying cardiovascular disease.
• Uncontrolled hypothyroidism. May have hypothyroidism if taking adequate and stable thyroid replacement medication.

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