PTSDPhase 2NCT03282123
Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD
A Phase 2 study testing Midomafetamine and Manualized therapy in people with PTSD, run by Resilient Pharmaceuticals at 12 sites in United States.
Trial summary
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people diagnosed with at least severe PTSD. The main question it aims to answer is: Do three open-label sessions of MDMA-assisted therapy reduce PTSD symptoms? Participants will receive three non-drug preparatory sessions… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PTSD
- What is being tested?
- Midomafetamine and Manualized therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 12 sitesUnited States
- Study dates
- 16 Nov 2017to 10 Aug 2019
- 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
- Are at least 18 years old
- Are fluent in speaking and reading the predominantly used or recognized language of the study site
- Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
- Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
- Must agree to inform the investigators within 48 hours of any medical conditions and procedures
- If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session.
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- Must not participate in any other interventional clinical trials during the duration of the study,
- Must be willing to remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures
- Meet DSM-5 Criteria for Severe PTSD
Who cannot join
- Are not able to give adequate informed consent
- Have uncontrolled hypertension
- Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula)
- Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- Have evidence or history of significant medical disorders
- Have symptomatic liver disease
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- Have history of hyponatremia or hyperthermia
- Weigh less than 48 kilograms (kg)
- Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control.
- Meet DSM-5 criteria for active substance use disorder for any substance other than caffeine or nicotine
- Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental Session.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Aguazul-Blue Water Inc.
Boulder, Colorado, 80302
Trauma Research Foundation
Brookline, Massachusetts, 02446
University of Connecticut
Farmington, Connecticut, 06030
Wholeness Center
Fort Collins, Colorado, 80525
University of Wisconsin at Madison
Madison, Wisconsin, 53705
Zen Therapeutic Solutions, LLC
Mt. Pleasant, South Carolina, 29464
Ray Worthy Psychiatry LLC
New Orleans, Louisiana, 70123
New York University
New York, New York, 10016
Affective Care
New York, New York, 10024
New School Research LLC
North Hollywood, California, 91601
San Francisco Insight and Integration Center
San Francisco, California, 94114
University of California San Francisco
San Francisco, California, 94122
About this study
Official title: An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people diagnosed with at least severe PTSD.
The main question it aims to answer is: Do three open-label sessions of MDMA-assisted therapy reduce PTSD symptoms?
Participants will receive three non-drug preparatory sessions followed by three sessions of MDMA-assisted therapy. Each MDMA-assisted therapy session is followed by three non-drug integrative therapy sessions.
Read the detailed description
This multi-site, open-label, Phase 2, lead-in study assesses the safety and efficacy of MDMA-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study.
This study will compare the effects of three open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to Primary Endpoint (Visit 19).
- Conditions
- PTSD
- Being tested
- Midomafetamine, Manualized therapy
- Keywords
- MDMA, methylenedioxymethamphetamine, therapy, midomafetamine
- 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.
MidomafetamineDrug
Also called 3,4-methylenedioxymethamphetamine, MDMA
80 to 120 mg MDMA
Manualized therapyBehavioural
Non-directive therapy conducted during MDMA-assisted therapy session
| Study group | Role | What they receive |
|---|---|---|
| MDMA-assisted therapy | Experimental | Three sessions of MDMA-assisted therapy with flexible dose of midomafetamine HCl from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later Receives: Drug: Midomafetamine; Behavioral: Manualized therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores
The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. 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 to 18 weeks post-enrollment
Secondary outcomes (1)
Change From Baseline to Visit 19 in Adapted SDS Total Score
The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.
Measured: Baseline to 18 weeks post-enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2017
- Study start16 Nov 2017
- Primary completion10 Aug 2019
- Study completion10 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Model description
- Three sessions of MDMA-assisted therapy with flexible dose of MDMA (80 to 120 mg with optional supplemental half-dose)
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Resilient Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael C Mithoefer, MD, Study director, MAPS Public Benefit Corp.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03282123
- Sponsor's protocol ID
- MP-16
- Status last verified
- May 2025
- First submitted
- 11 Sep 2017
- Last updated
- 5 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Christie D, Yazar-Klosinski B, Nosova E, Kryskow P, Siu W, Lessor D, Argento E. MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder. Front Psychiatry. 2022 Nov 3;13:939302. doi: 10.3389/fpsyt.2022.939302. eCollection 2022.
PubMed 36405923
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT03282123
- Acronym / sponsor ID
- MP-16
- Conditions
- PTSD
- Keywords
- MDMA, methylenedioxymethamphetamine, therapy, midomafetamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Resilient PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Nov 2017 (actual)
- Primary completion
- 10 Aug 2019 (actual)
- Study completion
- 10 Aug 2019 (actual)
- First posted
- 13 Sep 2017 (actual)
- Results
- Posted 29 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people diagnosed with at least severe PTSD.
The main question it aims to answer is: Do three open-label sessions of MDMA-assisted therapy reduce PTSD symptoms?
Participants will receive three non-drug preparatory sessions followed by three sessions of MDMA-assisted therapy. Each MDMA-assisted therapy session is followed by three non-drug integrative therapy sessions.
Detailed description
This multi-site, open-label, Phase 2, lead-in study assesses the safety and efficacy of MDMA-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study.
This study will compare the effects of three open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to Primary Endpoint (Visit 19).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Three sessions of MDMA-assisted therapy with flexible dose of MDMA (80 to 120 mg with optional supplemental half-dose)
| Arm | Type | Receives |
|---|---|---|
| MDMA-assisted therapy | Experimental | Drug: Midomafetamine, Behavioral: Manualized therapyThree sessions of MDMA-assisted therapy with flexible dose of midomafetamine HCl from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Are at least 18 years old
- Are fluent in speaking and reading the predominantly used or recognized language of the study site
- Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
- Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
- Must agree to inform the investigators within 48 hours of any medical conditions and procedures
Key exclusion criteria (11 listed)
- Are not able to give adequate informed consent
- Have uncontrolled hypertension
- Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula)
- Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- Have evidence or history of significant medical disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MidomafetamineAlso: 3,4-methylenedioxymethamphetamine, MDMA80 to 120 mg MDMA | Drug | MDMA-assisted therapy |
| Manualized therapyNon-directive therapy conducted during MDMA-assisted therapy session | Behavioural | MDMA-assisted therapy |
Primary outcome
Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores
Time frame: Baseline to 18 weeks post-enrollment
The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. 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.
1 secondary outcome
Change From Baseline to Visit 19 in Adapted SDS Total Score
Time frame: Baseline to 18 weeks post-enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36405923Christie D, Yazar-Klosinski B, Nosova E, Kryskow P, Siu W, Lessor D, Argento E. MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder. Front Psychiatry. 2022 Nov 3;13:939302. doi: 10.3389/fpsyt.2022.939302. eCollection 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael C Mithoefer, MD study director
MAPS Public Benefit Corp.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Midomafetamine and Manualized therapy in people with PTSD, run by Resilient Pharmaceuticals at 12 sites 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 9 inclusion and 11 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 12 sites 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 29 Jul 2021). 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 From Baseline to Visit 19 in CAPS-5 Total Severity Scores (time frame: Baseline to 18 weeks post-enrollment). 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 NCT03282123, which also lists 1 linked publication.
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.