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Post-Traumatic Stress DisorderPhase 3MDMA-PENCT06117306

MDMA-assisted Massed Prolonged Exposure for PTSD

A Phase 3 study testing 3,4 Methylenedioxymethamphetamine and Prolonged Exposure in people with Post-Traumatic Stress Disorder, run by Healing Breakthrough at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The overall objective of this study is to pilot the VASDHS-adapted Emory MDMA-PE Protocol (aE-MDMA-PE) and assess the effect on clinician-rated PTSD symptoms in veterans who receive different doses of MDMA. Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Post-Traumatic Stress Disorder
What is being tested?
3,4 Methylenedioxymethamphetamine and Prolonged Exposure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
25 Oct 2024to Mar 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Be a veteran (age 18-64 years old) who meets criteria for PTSD on the CAPS-5 (severity ≥ 25).
  • Be fluent in speaking and reading English.
  • Are willing to commit to medication dosing, therapy sessions, follow-up sessions, completing evaluation instruments, and all necessary telephone contact
  • Be able to swallow pills.
  • Agree to have study visits audio and/or video recorded, including MDMA session, assessments, and PE sessions, and aware that Independent Rater assessments for PE sessions will occur.
  • Have a contact able to drive the participant home after the MDMA session.
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  • 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 inform the investigators within 48 hours of any new medical conditions or procedures.
  • If able to become pregnant (i.e., assigned female at birth, fertile, following menarche and until becoming post-menopausal unless permanently sterile), must have a highly sensitive negative pregnancy test at study entry and prior to the MDMA session, and must agree to use adequate birth control for 1 month before through 10 days after the MDMA 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).
  • Agree to the following lifestyle modifications (described in more detail in Section 3.3 Lifestyle Modifications): comply with requirements for fasting and refraining from certain medications prior to and following the MDMA session, including a possible medication taper if on SSRIs, medications for ADHD, and/or other medications described in the concomitant medications section.
  • Agree not to participate in other PTSD psychotherapy during study treatment.
  • Not enroll in any other interventional clinical trials during the duration of the study, and commit to medication dosing, therapy, and study procedures.
  • At Pre-Screening, have at least moderate PTSD symptoms in the last month based on PCL-5 total score of 40 or greater (index).
  • May have well-controlled hypertension that has been successfully treated with anti- hypertensive medicines if they pass additional screening to rule out underlying cardiovascular disease.
  • May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.
  • May have alcohol or substance use disorder if participant is not in withdrawal or requiring detox. Participants must have a plan, agreed upon by investigator, therapy team, and study physician, to reduce use of alcohol or other substances and to manage symptoms without self-medicating. Enrollment will require that, in the judgment of the investigator, therapy team, and study physician, the plan for decreasing substance use is realistic and has a good chance of succeeding in order to prevent substance use from impacting the safety or effectiveness of the investigational treatment. Veterans will also be subject to a urine toxicology drug screening prior to enrollment and before the MDMA session.
  • 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 study physician.
  • 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.

Who cannot join

  • Are not able to give adequate, written informed consent.
  • Are currently engaged in compensation and pension (C\&P) litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders.
  • Are likely, in the investigator's opinion and via assessment period, to be re- exposed to their index trauma or other significant trauma, lack social support, or lack a stable living situation.
  • Have used Ecstasy (material represented as containing MDMA) or have participated in an MDMA clinical trial.
  • Have a positive screen for amphetamine or cocaine.
  • Have any current problem which, in the clinical opinion of the investigator and study physician, might interfere with participation due to it impacting the patient's safety and/or ability to participate in the protocol.
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  • Have hypersensitivity to any ingredient of the IMP (Investigational Medicinal Product).
  • Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment.
  • Have dementia.
  • Have a history of or a current primary psychotic disorder assessed via the DIAMOND and clinical interview.
  • Have a history of or current Bipolar 1 disorder, Bipolar 2 disorder, or manic episode assessed via the DIAMOND and clinical interview.
  • Have a current eating disorder with active purging assessed via DIAMOND and clinical interview.
  • Have current major depressive disorder with psychotic features assessed via DIAMOND.
  • Have a current panic disorder assessed via the DIAMOND
  • Have a history of amphetamine or cocaine substance use disorder
  • Have a current alcohol or substance use disorder other than caffeine or nicotine that the investigators, therapy team, and/or study physician judge to be a safety concern for enrollment in the study or that could interfere with the therapeutic process or with other aspects of study participation. Any participant who is not able to agree or adhere to a plan to reduce use and manage symptoms will not be enrolled. Individuals endorsing severe symptoms of an active alcohol use disorder (AUDIT >8 for men, >6 for women) or of an active substance use disorder (DUDIT >6 for men, >2 for women) will be evaluated by the study PI and/or physicians to determine if they should be excluded.
  • Present with current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS (scores of four or greater), and clinical judgment of the investigator; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled. Any participant presenting with the following on the pre-screen C-SSRS will be excluded:
  • Suicidal ideation score of 4 or greater within the last 6 months of the assessment at a frequency of once a week or more.
  • 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.
  • Would present a serious risk to others as established through clinical interview and if necessary, discussion with treating psychiatrist.
  • Require ongoing concomitant therapy with a psychiatric medication other than the exceptions described in protocol section on Concomitant Medications.
  • 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 study physician and PI 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 IMP. Examples of stable medical conditions that could be allowed include, but are not limited to 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 a diagnosis of uncontrolled hypertension defined by the American Heart Association as repeated readings of ≥ 140 millimeters of Mercury [mmHg] systolic or ≥ 90 mmHg diastolic.
  • Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease.
  • Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
  • Have a history of arrhythmia, other than premature atrial contractions (PACs) or occasional PVCs in the absence of ischemic heart disease, within 12 months of screening. Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled only if they have been successfully treated with ablation and have not had recurrent arrhythmia for at least one year off all antiarrhythmic drugs and confirmed by a cardiologist.
  • Have a marked Baseline prolongation of QT/QTc interval. For purposes of eligibility, this is defined as repeated demonstration of a QT interval corrected using Fridericia's formula [QTcF] >450 milliseconds [ms].
  • Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  • Require use of concomitant medications that prolong the QT/QTc interval during Sessions. Refer to protocol section on Concomitant Therapy.
  • Have symptomatic liver disease or have repeated significant liver enzyme elevations on labs.
  • Have history of hyponatremia or hyperthermia.
  • Have a BMI of 18.5 or less.
  • Are pregnant or nursing or are able to become pregnant and are not willing/able to practice an effective means of birth control.
  • Have engaged in ketamine-assisted therapy or used ketamine within 12 weeks of enrollment.
  • Have any preexisting condition affecting renal functioning.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • VA San Diego Healthcare System, San Diego, CA

    San Diego, California, 92161

Other trials in United States

About this study

The overall objective of this study is to pilot the VASDHS-adapted Emory MDMA-PE Protocol (aE-MDMA-PE) and assess the effect on clinician-rated PTSD symptoms in veterans who receive different doses of MDMA.

Read the detailed description

The study is a randomized pilot study that will evaluate the preliminary efficacy, safety, tolerability, and acceptability of the intervention in a sample of U.S. veterans seeking PTSD treatment at the VASDHS. Ten to twenty veterans will be randomized to receive a dose of MDMA (exact range not disclosed) based on the 2-week Emory MDMA-PE Protocol developed by Maples-Keller and Rothbaum. The current protocol will entail massed-PE and the MDMA administration spanning approximately 3-weeks. PE will involve twelve 90-minute sessions with the initial two sessions both occurring during the first treatment visit, the third and fourth sessions occurring during the MDMA session, and the remaining sessions occurring daily or every other day (M-F for two to three weeks).

Following the baseline assessment during Visit 1, participants will begin PE during Visit 2, which will include psychoeducation, rationale for exposure-based treatment, discussion of the SUDS scale, and creating the in vivo exposure hierarchy. Visit 3 will be the Preparatory Session, in which we will provide psychoeducation regarding MDMA's subjective effects and strategies for MDMA-related support. Visit 4 will include the MDMA administration, which will include the third and fourth PE sessions, including the first and second imaginal exposures. Participants will report SUDS at the start and end of imaginal exposure. At the beginning of Visit 5, following a modified version of the MAPS Integration session criteria, the therapist and patient will focus on developing a deeper understanding of insights from the MDMA session and any thoughts or feelings regarding the patient's experience of PTSD and its impact on their life. After the Integration session there will be a break before the PE session. Visits 5-12 will include imaginal exposures and processing of the in-session experience. Imaginal exposures will be recorded, and participants will listen to this recording as homework. Each visit an in vivo exposure will be assigned for homework; all sessions will begin with a check-in that includes reviewing this exposure experience. The post-treatment questionnaire assessment will occur on Visit 13. Participants will complete post-treatment follow-up CAPS-5 clinical interviews remotely approximately 1 week, 2 months, and 4 months after treatment. Following the 2-month follow-up assessment and unblinding, veterans may be offered an optional additional MDMA session and up to three optional additional integration sessions depending on the dose they received.

Participants will be invited to enroll in an optional fMRI (brain imaging) sub-study where, if eligible and interested, they will undergo fMRI brain scans pre- and post-treatment.

Being tested
3,4 Methylenedioxymethamphetamine, Prolonged Exposure
Keywords
Post Traumatic Stress Disorder, MDMA, 3,4-methylenedioxymethamphetamine, Veterans, Prolonged Exposure Therapy
Medical subject headings
Stress Disorders, Post-Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 3,4 MethylenedioxymethamphetamineDrug

    Also called MDMA

    1 MDMA session

  • Prolonged ExposureBehavioural

    Also called PE

    12 90-minute PE sessions; initial two sessions both occurring during the first treatment visit, third and fourth sessions occurring during the MDMA session, and the remaining sessions occurring daily or every other day

Study groups in NCT06117306
Study groupRoleWhat they receive
Dose A (exact dose not disclosed)ExperimentalNon-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA) PE Non-medicine sessions: 12 sessions MDMA Medicine session: Dose: exact dose not disclosed
Receives: Drug: 3,4 Methylenedioxymethamphetamine; Behavioral: Prolonged Exposure
Dose B (exact dose not disclosed)ExperimentalNon-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA) PE Non-medicine sessions: 12 sessions MDMA Medicine session: Dose: exact dose not disclosed
Receives: Drug: 3,4 Methylenedioxymethamphetamine; Behavioral: Prolonged Exposure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinician-rated PTSD symptoms

    The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 20-item diagnostic interview administered by trained evaluators to assess PTSD in a participant. Based on DSM-5 diagnostic criteria, evaluators ask about the severity of four PTSD-related symptom clusters: re-experiencing, avoidance, negative alterations in cognition and mood, and alterations in arousal and reactivity. The evaluator rates responses on a 5-point Likert scale (0 = Absent to 4 = Extreme/Incapacitating). Total scores range from 0 to 80 with higher scores indicating greater severity.

    Measured: Baseline - 4-months post-treatment

Secondary outcomes (12)

  1. Self-reported PTSD symptoms

    The PTSD Checklist for DSM-5 (PCL-5) is a 20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms. Participants indicate how much distress they have experienced due to symptoms on a five-point Likert-type scale (1=Not at all to 5=Extremely). Total scores range from 0 to 80, with higher scores indicating more severe PTSD symptoms.

    Measured: Baseline - 4-months post-treatment

  2. Depressive Symptoms

    The Patient Health Questionnaire 9 (PHQ-9) is a 9-item self-report measure of depressive symptoms. The PHQ-9 screens for major depression, with a score of 10 or above indicative of a possible major depressive episode, and it provides a measure of severity of these symptoms.

    Measured: Baseline - 4-months post-treatment

  3. Functioning

    The Brief Inventory of Psychosocial Functioning (B-IPF) is a brief version of the Inventory of Psychosocial Functioning (IPF) that measures functioning impairment across seven domains: intimate relationships, family and parenting, friendships, work, socializing, education, and self-care over the past 30 days. Total scores, ranging from 0 to 100, are calculated as the sum score divided by the total possible score multiplied by 100, with higher scores indicating greater impairment in functioning.

    Measured: Baseline - 4-months post-treatment

  4. Sleep

    The Pittsburgh Sleep Quality Index (PSQI) measures sleep quality over the past 1-month using 19 items in a self-report questionnaire format. The scale has seven subcategories: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Items are rated on a combination of Likert scales from 0 to 3 and open- ended questions that are later converted to scaled scores. Higher total scores indicate greater sleep disturbance.

    Measured: Baseline - 4-months post-treatment

  5. Safety/Suicidality

    The C-SSRS is a clinician-administered measure of suicidal behavior devised to detect potential suicidal thoughts or behaviors during a clinical trial. It consists of a Baseline version and a Since Last Visit version that assess suicidal ideation, ideation intensity, and behavior.

    Measured: Baseline - 4-months post-treatment

  6. Sexual Functioning

    The CSFQ-14 is a 14-item self-report scale that evaluates sexual functioning. The measure has five subscales: pleasure, desire/frequency, desire/interest, arousal/excitement, and orgasm/completion. All items are scored on 5-point scales with varying response options. Higher total scores indicate better sexual functioning. The CSFQ-14 has corresponding assigned-male-at-birth and assigned-female-at-birth versions.

    Measured: Baseline - 4-months post-treatment

  7. Moral Injury

    The MIDS is a two-part self-report measure that examines potentially morally injurious events (PMIEs) exposure and moral injury symptoms in the past month. The first part of the scale uses 6 items to measure exposure to and bothersomeness of PMIEs through a 5-point Likert scale (0=Not at all to 4=Extremely). The second part of the scale includes a series of open-ended questions to select and describe the most distressing PMIE. Respondents then complete 18 items that are scored on 5-point Likert scales to indicate their cognitive, emotional, behavioral, social, and religious or spiritual reactions to the PMIE that they find the most distressing. Higher summed score indicates more severe moral distress.

    Measured: Baseline - 4-months post-treatment

  8. Adverse Childhood Experiences

    Measured using the Adverse Childhood Events Scale (ACES). The ACES is a 10-item self-report survey that asks about childhood stress. Participants indicate exposure to different kinds of abuse with yes/no responses, and answer "1" if the abuse happened often. Higher scores indicate greater exposure to childhood stressors.

    Measured: Baseline

  9. Posttraumatic Growth

    Measured using the Posttraumatic Growth Inventory (PTGI). The PTGI is a 21-item self-report measure that asks about level of posttraumatic growth across 5 subscales in adults who have experienced trauma. Participants respond using a 6-point Likert scale (1=I did not experience this change as a result of my crisis, to 6=I experienced this change to a very great degree as a result of my crisis).Total scores range from 1-126.

    Measured: Baseline - 4-months post-treatment

  10. Anger

    The STAXI-2 is a 57-item self-report measure that assesses the respondent's experience, expression, and control of anger. The measure includes six scales; for the purpose of this study, only the state anger state anger (i.e., the intensity of anger at the time of completing the scale; 15 items) and trait anger (i.e., whether the person has an overall angry temperament; 10 items) scales will be used, for a total of 25 items. All items are rated on a scale from 1 (Almost never) to 4 (Almost always). Both scales are scored by summing responses to each item, with higher scores indicating higher state and/or trait anger. Ranges are 15-60 for the state scale and 10-40 for the trait scale.

    Measured: Baseline - 4-months post-treatment

  11. Well Being

    Measured using the Well-Being Signs (WBS). The WBS is a 3-item self-report measure examining psychosocial well-being. All items are rated on a scale from 0 to 10. An average score is calculated based on the ratings for each question. Higher scores indicate better psychosocial well-being.

    Measured: Baseline - 4-months post-treatment

  12. Positive and Negative Affect

    Measured using the Positive and Negative Affect Schedule (PANAS). The PANAS is a 20-item self-report measure of positive affect and negative affect, with a 10-item positive affect subscale and 10-item negative affect subscale. Items are rated on a scale from 1 (very slightly or not at all) to 5 (extremely). Higher scores on each subscale indicate more positive and negative affect respectively.

    Measured: Baseline - 4-months post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2023
  2. Study start25 Oct 2024
  3. Primary completionMar 2027 (estimated)
  4. Study completionMar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Eligible participants will be randomized in a stratified 1:1 manner to receive a dose of MDMA (exact doses not disclosed).
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06117306
Sponsor's protocol ID
IVAPT4
Acronym
MDMA-PE
Status last verified
Aug 2026
First submitted
27 Oct 2023
Last updated
26 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 3,4 Methylenedioxymethamphetamine and Prolonged Exposure in people with Post-Traumatic Stress Disorder, run by Healing Breakthrough at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinician-rated PTSD symptoms (time frame: Baseline - 4-months post-treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06117306.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

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