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Posttraumatic Stress DisorderPhase 2NCT01793610

Dose-Response Study of MDMA-assisted Psychotherapy in People With PTSD

A Phase 2 study testing Comparator Dose (40mg) MDMA HCl, Active Dose 2 (100 mg) MDMA HCl and Active Dose 1 (125 mg) MDMA HCl in people with Posttraumatic Stress Disorder, run by Resilient Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this clinical trial is to learn if MDMA in combination with therapy is safe and effective in people with chronic, treatment-resistant PTSD. The main questions it aims to answer are: Does MDMA-assisted therapy reduce PTSD symptoms? Is there a difference in PTSD symptoms between the 40 mg, 100 mg, and 125 mg… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Posttraumatic Stress Disorder
What is being tested?
Comparator Dose (40mg) MDMA HCl, Active Dose 2 (100 mg) MDMA HCl and Active Dose 1 (125 mg) MDMA HCl
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
13 May 2013to 1 Feb 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosed with chronic PTSD for six months or longer.
  • Have a CAPS score showing moderate to severe PTSD symptoms.
  • At least one unsuccessful attempt at treatment for PTSD either with talk therapy or with drugs, or discontinuing treatment because of inability to tolerate psychotherapy or drug therapy.
  • Are at least 18 years old.
  • Must be generally healthy.
  • Are willing to refrain from taking any psychiatric medications during the study period.
Show all 16Show fewer
  • Willing to follow restrictions and guidelines concerning consumption of food, beverages or nicotine the night before and just prior to each MDMA session.
  • Willing to remain overnight at the study site.
  • Are willing to be driven home after experimental sessions either by a driver they arrange, a taxi, or study personnel.
  • Are willing to be contacted via telephone by study personnel.
  • If of child-bearing age, must have a negative pregnancy and agree to use an effective form of birth control.
  • Must provide a personal contact who is willing to be reached in case of emergency.
  • Agree to let the investigators know within 48 hours of any planned medical interventions.
  • Are proficient in reading and speaking English.
  • Agree to have all psychotherapy sessions recorded.
  • Agree not to participate in any other interventional clinical trials during the course of the study.

Who cannot join

  • Are pregnant or nursing, or if of child-bearing age and do not use an effective means of birth control.
  • Weigh less than 48 kg.
  • Meet DSM-IV criteria for substance abuse or dependence for any substance in the past 60 days.
  • Have used "Ecstasy" (material represented as containing MDMA) more than five times in the last ten years or at least once within 6 months of the MDMA session.
  • Are unable to give adequate informed consent.
  • Upon review of past and current drugs/medication, must not be on or have taken a medication that is exclusionary.
  • Upon review of medical or psychiatric history, must not have any current or past diagnosis that would be considered a risk to participation in the study.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Offices of Marcela d'Otalora

    Boulder, Colorado, 80304

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Dose Response Phase 2 Pilot Study of Manualized MDMA-Assisted Psychotherapy in Subjects With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)

The goal of this clinical trial is to learn if MDMA in combination with therapy is safe and effective in people with chronic, treatment-resistant PTSD.

The main questions it aims to answer are:

Read more
  • Does MDMA-assisted therapy reduce PTSD symptoms?
  • Is there a difference in PTSD symptoms between the 40 mg, 100 mg, and 125 mg groups?

Researchers will compare two active doses (100 mg and 125 mg) of MDMA-assisted therapy versus a comparator dose of 40 mg MDMA-assisted therapy to determine if there is a reduction in PTSD symptoms.

Participants will undergo three non-drug preparatory sessions, three MDMA-assisted therapy sessions and three non-drug integrative therapy sessions after each MDMA-assisted therapy session.

Read the detailed description

This Phase 2 pilot study is a randomized, double-blind, dose response study to examine the safety and efficacy of MDMA-assisted psychotherapy in 23 subjects with chronic, treatment-resistant PTSD of at least six months duration. This study assessed two active doses of MDMA, active dose 1 (100 mg) and active dose 2 (125 mg), to a comparator dose of MDMA (40 mg) during psychotherapy sessions. The initial dose of MDMA was followed 1.5 to 2.5 hours later by an optional supplemental dose of MDMA that was half the size of the first dose. MDMA was administered orally in two experimental sessions lasting up to eight hours and scheduled three to five weeks apart.

Subjects were prepared for MDMA-assisted psychotherapy in three preparatory sessions prior to the first experimental session, and worked with the same pair of therapists throughout the study. After each experimental session, three integrative sessions were scheduled with the subject, including one integrative session the morning after the experimental session. During integrative sessions, subjects processed and connected their thoughts and feelings about the experience with their therapist team.

Subjects who received the comparator dose (40 mg) were given the option to enroll in Stage 2, where they underwent three open-label MDMA-assisted psychotherapy sessions. 100 mg of MDMA was administered in the first session and therapists determined whether to increase to 125 mg of MDMA for the second and third experimental sessions. People who received 125 mg of MDMA during the first two experimental sessions received the same dose during an open-label third experimental session. People who received 100 mg of MDMA during the first two sessions were able to choose, in consultation with their therapist, to either continue to receive 100 mg in a third session or to increase their dose to 125 mg.

A blinded independent rater (IR) assessed the severity of PTSD symptoms at baseline, one month after the second experimental session (the primary endpoint), two months after the third open-label experimental session, and at equivalent points in Stage 2.

Being tested
Comparator Dose (40mg) MDMA HCl, Active Dose 2 (100 mg) MDMA HCl, Active Dose 1 (125 mg) MDMA HCl, Psychotherapy
Keywords
MDMA, Posttraumatic stress disorder, sleep, Depression, Safety
Medical subject headings
Stress Disorders, Post-Traumatic, Depression

What participants receive

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

  • Comparator Dose (40mg) MDMA HClDrug

    Also called 3,4-methylenedioxymethamphetamine, midomafetamine HCl, midomafetamine, MDMA

    An initial comparator-dose of 40 mg midomafetamine HCl orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (20 mg).

  • Active Dose 2 (100 mg) MDMA HClDrug

    Also called 3,4-methylenedioxymethamphetamine, midomafetamine HCl, midomafetamine, MDMA

    An initial dose of full-dose 100 mg midomafetamine HCl orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (50 mg).

  • Active Dose 1 (125 mg) MDMA HClDrug

    Also called 3,4-methylenedioxymethamphetamine, midomafetamine HCl, midomafetamine, MDMA

    An initial dose of full-dose 125 mg midomafetamine HCl orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (62.5 mg).

  • PsychotherapyBehavioural

    Also called Manualized MDMA-assisted psychotherapy

    Non-directive manualized therapy

Study groups in NCT01793610
Study groupRoleWhat they receive
Comparator Dose (40 mg) MDMA-assisted therapyActive comparatorParticipants receive an initial dose of comparator dose midomafetamine HCl (40 mg) during each of two therapy sessions.
Receives: Drug: Comparator Dose (40mg) MDMA HCl; Behavioral: Psychotherapy
Active Dose 2 (100 mg) MDMA-assisted therapyExperimentalParticipants receive an initial dose of Active Dose 2 midomafetamine HCl (100 mg) during each of two therapy sessions.
Receives: Drug: Active Dose 2 (100 mg) MDMA HCl; Behavioral: Psychotherapy
Active Dose 1 (125 mg) MDMA-assisted therapyExperimentalParticipants receive an initial dose of Active Dose 1 midomafetamine HCl (125 mg) during each of two therapy sessions.
Receives: Drug: Active Dose 1 (125 mg) MDMA HCl; Behavioral: Psychotherapy

What is being measured

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

  1. Change in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) Total Severity Score From Baseline to One Month Post 2nd Experimental Session

    The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.

    Measured: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

Secondary outcomes (6)
  1. Change in PTSD Diagnostic Scale (PDS) From Baseline to One Month Post 2nd Experimental Session

    The PTSD Diagnostic Scale (PSD) is self-report measure designed to follow DSM-IV criteria for assessing PTSD. It contains 49 items, with responses made on a four-point scale, ranging from 0 ("not at all") to 3 ("five or more times a week"). The PDS consists of a list of 12 potential traumatic events, 12 items addressing elements of the traumatic event, 17 symptom items, and 9 items assessing impact on areas of life function. Items addressing elements of the traumatic event and life function are answered as either present or not present (Yes or No). The 17 items are summed to create a symptom severity score, with higher scores indicating a greater number and/or intensity of PTSD symptoms. The symptom severity score ranges from 0 to 51.

    Measured: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

  2. Change in Beck Depression Inventory II (BDI-II) From Baseline to One Month Post 2nd Experimental Session

    Validated self-report measure of symptoms of depression. The BDI-II total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe depressive symptoms. The scores range from 0 to 63, with higher score indicating greater severity of depressive symptoms.

    Measured: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

  3. Change in Global Assessment of Functioning (GAF) Total Score From Baseline to One Month Post 2nd Experimental Session

    The Global Assessment of Functioning (GAF) Scale is a numeric scale ranging from 0 through 100 that is used by mental health clinicians and physicians to subjectively rate the social, occupational, and psychological functioning of adults. Higher scores indicate better functioning.

    Measured: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

  4. Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to One Month Post 2nd Experimental Session

    The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances. It is comprised of 18 items that yield seven component scores. Component scores are summed to create a total score. Total scores range from 0 (better) to 21 (worse), with higher scores indicating poor sleep quality.

    Measured: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

  5. Change in Dissociative Experiences Scale (DES-II) From Baseline to One Month Post 2nd Experimental Session

    The DES-II is a 28-item self-report measure of dissociation, defined as a lack of normal integration of an individual's thoughts, feelings, or experiences into the stream of consciousness or memory. The scale consists of statements describing facets of dissociation. Respondents indicate how often the specific experience happens to them, from "never" to "always." The DES-II uses the same items but with responses made on a 10 point scale from "0%" to "100%" of the time. The scale is scored by treating percentages as single digits to produce a total score with higher scores indicating greater severity. The total score ranges from 0 to 100.

    Measured: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

  6. Change in Posttraumatic Growth Inventory (PTGI) From Baseline to One Month Post 2nd Experimental Session

    The PTGI is a 21-item self-report measure of perceived growth or benefits occurring after a traumatic event. It contains five subscales: relationship to others, new possibilities, personal strength, spiritual change, and appreciation of life. PTGI scores on a 6 point scale are: 0 - I did not experience this as a result of my crisis; 1 - I experienced this change to a very small degree as a result of my crisis; 2 - I experienced this change to a small degree as a result of my crisis; 3 - I experienced this change to a moderate degree as a result of my crisis; 4 - I experienced this change to a great degree as a result of my crisis; and 5 - I experienced this change to a very great degree as a result of my crisis. A total score is calculated by summing the responses to all 21 items, each rated on a 6-point scale, with higher scores indicating greater post-traumatic growth

    Measured: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

Timeline

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

  1. First posted15 Feb 2013 (estimated)
  2. Study start13 May 2013
  3. Primary completion3 Dec 2015
  4. Study completion1 Feb 2017

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01793610
Sponsor's protocol ID
MP-12
Status last verified
May 2025
First submitted
13 Feb 2013
Last updated
5 Jun 2025
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995 Jan;8(1):75-90. doi: 10.1007/BF02105408.

    PubMed 7712061
  • Beck AT, Steer RA. Internal consistencies of the original and revised Beck Depression Inventory. J Clin Psychol. 1984 Nov;40(6):1365-7. doi: 10.1002/1097-4679(198411)40:63.0.co;2-d.

    PubMed 6511949
  • Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996 Dec;67(3):588-97. doi: 10.1207/s15327752jpa6703_13.

    PubMed 8991972
  • Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020 Aug;237(8):2485-2497. doi: 10.1007/s00213-020-05548-2. Epub 2020 Jun 4.

    PubMed 32500209
  • Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry. 2019 Sep 12;10:650. doi: 10.3389/fpsyt.2019.00650. eCollection 2019.

    PubMed 31572236
  • Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7.

    PubMed 31065731

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Comparator Dose (40mg) MDMA HCl, Active Dose 2 (100 mg) MDMA HCl and Active Dose 1 (125 mg) MDMA HCl in people with Posttraumatic Stress Disorder, run by Resilient Pharmaceuticals 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 16 inclusion and 7 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: finished, as of the sponsor's last update on 5 Jun 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) Total Severity Score From Baseline to One Month Post 2nd Experimental Session (time frame: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)). 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 NCT01793610, which also lists 6 linked publications.

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 5 Jun 2025.

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