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

NCT07704762 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: S-25-01Award # HT9425-25-1-0846IUSPT5WRNMMC-2026-0517
• Study Type: interventional
• Target: 86
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

PTSD; Post Traumatic Stress Disorder PTSD; Post Traumatic Stress Disorder

Keywords

Post-Traumatic Stress Disorder (PTSD); Acceptance and Commitment Therapy (ACT); Service Members; Trauma; Psychotherapy Modality; Psychiatric Disorders; 3,4-Methylenedioxymethamphetamine; MDMA; Active Duty; MDMA-Assisted Therapy; Phase II; Active Controlled; Psychedelic-Assisted Therapy

Outcome Measures

Primary Outcomes (1)

• Change in Revised Clinician Administered PTSD Scale for DSM-5 (CAPS-5-R) Total Severity Score From Baseline to Primary Outcome

  The primary objective of this study is to determine treatment efficacy of MDMA-AT for PTSD by comparing PTSD symptom severity as measured by independent raters with the CAPS-5-R \[Revised Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)\] as measured from baseline to the primary endpoint which is 1 month after the third dosing session. The CAPS-5-R is a structured clinician-administered measure that assesses the presence and severity of PTSD per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. All the DSM-5 symptoms of PTSD are assessed and rated on a scale from 0 (Absent) to 10 (Extremely Severe), with clear anchors provided to clinicians to assist with accurate ratings. The range of the scale is 0-200.The higher the score at baseline, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.

  The primary endpoint will be 14±3 weeks after the baseline independent rater CAPS-5-R visit and 1-9 days after the final Integration Session.

Secondary Outcomes (1)

• Change in Revised Clinician-Administered PTSD Scale for DSM-5 (CAPS-5-R) Total Severity Score From Primary Endpoint to Secondary Endpoint

  13±2 weeks after the third Dosing Session (~2 months from the Primary Endpoint)

Study Arms (2)

CONTROL ARM: Active-controlled

ACTIVE COMPARATOR

Low dose MDMA, 40mg

Drug: CONTROL ARM: Active-controlled

TREATMENT ARM: Full dose

EXPERIMENTAL

Full dose MDMA, 60mg to 120mg (maximum)

Drug: TREATMENT ARM: Full dose

Interventions

TREATMENT ARM: Full dose DRUG

Participants in this arm will receive full dose of MDMA integrated with Acceptance and Commitment Therapy (ACT)

Also known as: 3,4-Methylenedioxymethamphetamine, Psychedelic-Assisted Therapy

TREATMENT ARM: Full dose

CONTROL ARM: Active-controlled DRUG

Participants in this arm will receive lower dose of MDMA integrated with Acceptance and Commitment Therapy (ACT)

Also known as: 3,4-Methylenedioxymethamphetamine, Psychedelic-Assisted Therapy

CONTROL ARM: Active-controlled

Eligibility Criteria

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

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.

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
• 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.

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Resilient Pharmaceuticals: collaborator
• Walter Reed National Military Medical Center: collaborator
• Congressionally Directed Medical Research Programs: collaborator

Related Publications (2)

• Wolfgang AS, Fonzo GA, Gray JC, Krystal JH, Grzenda A, Widge AS, Kraguljac NV, McDonald WM, Rodriguez CI, Nemeroff CB. MDMA and MDMA-Assisted Therapy. Am J Psychiatry. 2025 Jan 1;182(1):79-103. doi: 10.1176/appi.ajp.20230681.

  PMID: 39741438 BACKGROUND

• Steenkamp MM, Litz BT, Hoge CW, Marmar CR. Psychotherapy for Military-Related PTSD: A Review of Randomized Clinical Trials. JAMA. 2015 Aug 4;314(5):489-500. doi: 10.1001/jama.2015.8370.

  PMID: 26241600 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Combat Disorders; Wounds and Injuries; Mental Disorders

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Study Officials

• Shannon Ford, MD

  WRNMMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexandra R Tribo

CONTACT

704-997-9460; alexandra.tribo.ctr@usuhs.edu

Amber Hampton, MSN

CONTACT

301-295-2397; Amber.Hampton.ctr@usuhs.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Phase 2, randomized, double-blind, active-controlled, single-site clinical trial

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 15, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share