PTSDPhase 3MAPPUSXNCT04714359
A Multi-Site Open-Label Extension Study of MDMA-Assisted Psychotherapy for PTSD
A Phase 3 study testing Midomafetamine HCl in people with PTSD, run by Resilient Pharmaceuticals at 15 sites in 3 countries.
Trial summary
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective at reducing PTSD symptoms in people with PTSD who received placebo in a prior MDMA-assisted therapy study. 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 HCl
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 15 sitesin 3 countries
- Study dates
- 8 Mar 2021to 6 Nov 2023
- Phase
- Phase 3
- 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
- Were previously enrolled in a parent study and (meet one of the following):
- At time of unblinding, their treatment assignment was to the placebo arm; or,
- Did not begin Experimental Sessions due to the COVID-19 global pandemic or other unforeseen circumstances;
- Completed fewer than three Experimental Sessions prior to Study Termination due to the COVID-19 global pandemic or other unforeseen circumstances.
- Are considered in good standing with the study site at which they enrolled in a parent study; if, in the opinion of the investigator, therapy team, and Medical Monitor, the participant was compliant with protocol requirements, even if they were unable to complete all study visits.
- Are at least 18 years old
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- Are fluent in speaking and reading the predominantly used or recognized language of the study site
- Are able to swallow pills
- 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.
- Must not participate in any other interventional clinical trials during the duration of the study
- Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions.
- 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.
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] in males and >460 ms in females corrected by Fridericia 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, such as myocardial infarction, cerebrovascular accident, or aneurysm
- Have symptomatic liver disease
- Have recent history of hyponatremia or hyperthermia
Show all 9Show fewer
- 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
- Have an active illicit or prescription drug substance use disorder within 12 months
Trial locations and contacts
15 sites in 3 countries.
15 sites in 3 countries
United States11 sites
Trauma Research Foundation
Boston, Massachusetts, 02446
Aguazul-Blue Water Inc.
Boulder, Colorado, 80302
Wholeness Center
Fort Collins, Colorado, 80525
New School Research
Los Angeles, California, 90004
University of Wisconsin - Madison
Madison, Wisconsin, 53705-2222
Zen Therapeutic Solutions, LLC
Mt. Pleasant, South Carolina, 29464
Ray Worthy Psychiatry
New Orleans, Louisiana, 70123
NYU
New York, New York, 10016
New York Private Practice
New York, New York, 11012
San Francisco Insight and Integration Center
San Francisco, California, 94114
UCSF
San Francisco, California, 94122
Canada2 sites
Numinus
Montreal, Quebec, H2W 1Y9
Numinus
Vancouver, British Columbia, V5R 5H3
Israel2 sites
Beer Yaakov Mental Health Center
Beer Yaaqov
Tel Hashomer
Tel Aviv
About this study
Official title: A Multi-Site Open-Label Safety Extension Study of Manualized MDMA-Assisted Psychotherapy for the Treatment of Participants With Posttraumatic Stress Disorder
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective at reducing PTSD symptoms in people with PTSD who received placebo in a prior MDMA-assisted therapy study.
The main question it aims to answer is:
Do PTSD symptoms decrease in people who receive a flexible dose of MDMA (120 or 180 mg MDMA HCl) with therapy in three sessions?
Participants will undergo three preparatory therapy sessions without any study drug, then three MDMA-assisted therapy sessions with a flexible dose of 80 or 120 mg, followed by three integrative therapy sessions without study drug after each MDMA-assisted therapy session.
Read the detailed description
This multi-site, open-label safety extension study assesses the efficacy and safety of MDMA-assisted psychotherapy versus psychotherapy in participants diagnosed with PTSD. The study will be conducted in N ≈ 100 participants. Participants who were randomized to the placebo arm in either of the two parent Phase 3 trials of MDMA-assisted psychotherapy and who meet all other entry criteria will be eligible and invited to participate in this study. In addition, participants in the parent Phase 3 trials who were unable to complete the study due to the COVID-19 pandemic or other unforeseen circumstances may participate in this study.
The treatment consists of an initial dose of midomafetamine HCl (80 or 120 mg), followed by a supplemental dose (40 or 60 mg) unless contraindicated, administered with manualized psychotherapy in three open-label Experimental Sessions each spaced approximately one month apart. During Experimental Session 1, participants will receive an initial dose of 80 mg of midomafetamine HCl, followed by a supplemental dose of 40 mg. During Experimental Sessions 2 and 3, participants will receive an initial dose of 80 or 120 mg of midomafetamine HCl, followed by a supplemental dose of 40 or 60 mg.
This 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. Experimental Sessions are followed by an overnight stay, with the exception of a subset of participants who will be invited to participate in a sub-study to assess the feasibility of Experimental Sessions without overnight stay. The primary study endpoint is the change from baseline in PCL-5 (PTSD Checklist for DSM-5) scores from Visit 3 to Visit 16.
- Conditions
- PTSD
- Being tested
- Midomafetamine HCl
- 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.
Midomafetamine HClDrug
Also called 3,4-methylenedioxymethamphetamine, MDMA HCl, midomafetamine, MDMA
Initial doses per Experimental Session include 80 mg or 120 mg midomafetamine HCl, followed 1.5 to 2 hours later by a supplemental dose unless tolerability issues emerge. For an initial dose of 80 mg, a 40 mg supplemental dose will be used. For an initial dose of 120 mg, a 60 mg supplemental dose will be used. Total amounts of midomafetamine HCl to be administered per Experimental Session range from 80 mg to 180 mg.
| Study group | Role | What they receive |
|---|---|---|
| MDMA-assisted therapy | Experimental | Three open-label sessions of MDMA-assisted therapy, each scheduled approximately 1 month apart, with initial dose of midomafetamine HCl of 80 or 120 mg and optional supplemental dose half that of initial dose (40 or 60 mg) 1.5 to 2 hours later Receives: Drug: Midomafetamine HCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Visit 16 in PCL-5 Total Score
The Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) is a 20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms, derived from the symptoms of PTSD per DSM-5. Participants indicate how much distress they have experienced in the last 2 weeks due to symptoms such as "Repeated, disturbing memories, thoughts, or images of a stressful experience from the past," "Trouble remembering important parts of a stressful experience from the past," and "Feeling irritable or having angry outbursts" on a five-point Likert-type scale (0=Not at all to 4=Extremely). The total severity score can range from 0 to 80 and lower scores indicate less PTSD symptoms.
Measured: Baseline enrollment to approximately 18 weeks later (Visit 16 occurs 24 to 32 days after Experimental Session 3)
Secondary outcomes (1)
Change From Baseline to Visit 16 in Sheehan Disability Scale (SDS) Total Score
The SDS is a self-report assessment of functional impairment. The reporting period for the SDS refers to the past month. The items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), with higher scores indicating greater functional impairment.
Measured: Baseline enrollment to approximately 18 weeks later (Visit 16 occurs 24 to 32 days after Experimental Session 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2021
- Study start8 Mar 2021
- Primary completion1 Nov 2023
- Study completion6 Nov 2023
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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Resilient Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04714359
- Sponsor's protocol ID
- MAPPUSX
- Acronym
- MAPPUSX
- Status last verified
- May 2025
- First submitted
- 14 Jan 2021
- Last updated
- 6 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share outcome data appearing in any published reports upon request.
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Site Open-Label Safety Extension Study of Manualized MDMA-Assisted Psychotherapy for the Treatment of Participants With Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT04714359
- Acronym / sponsor ID
- MAPPUSX / MAPPUSX
- Conditions
- PTSD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Resilient PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- 1 Nov 2023 (actual)
- Study completion
- 6 Nov 2023 (actual)
- First posted
- 19 Jan 2021 (actual)
- Results
- Posted 29 Nov 2024
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 at reducing PTSD symptoms in people with PTSD who received placebo in a prior MDMA-assisted therapy study.
The main question it aims to answer is:
Do PTSD symptoms decrease in people who receive a flexible dose of MDMA (120 or 180 mg MDMA HCl) with therapy in three sessions?
Participants will undergo three preparatory therapy sessions without any study drug, then three MDMA-assisted therapy sessions with a flexible dose of 80 or 120 mg, followed by three integrative therapy sessions without study drug after each MDMA-assisted therapy session.
Detailed description
This multi-site, open-label safety extension study assesses the efficacy and safety of MDMA-assisted psychotherapy versus psychotherapy in participants diagnosed with PTSD. The study will be conducted in N ≈ 100 participants. Participants who were randomized to the placebo arm in either of the two parent Phase 3 trials of MDMA-assisted psychotherapy and who meet all other entry criteria will be eligible and invited to participate in this study. In addition, participants in the parent Phase 3 trials who were unable to complete the study due to the COVID-19 pandemic or other unforeseen circumstances may participate in this study.
The treatment consists of an initial dose of midomafetamine HCl (80 or 120 mg), followed by a supplemental dose (40 or 60 mg) unless contraindicated, administered with manualized psychotherapy in three open-label Experimental Sessions each spaced approximately one month apart. During Experimental Session 1, participants will receive an initial dose of 80 mg of midomafetamine HCl, followed by a supplemental dose of 40 mg. During Experimental Sessions 2 and 3, participants will receive an initial dose of 80 or 120 mg of midomafetamine HCl, followed by a supplemental dose of 40 or 60 mg.
This 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. Experimental Sessions are followed by an overnight stay, with the exception of a subset of participants who will be invited to participate in a sub-study to assess the feasibility of Experimental Sessions without overnight stay. The primary study endpoint is the change from baseline in PCL-5 (PTSD Checklist for DSM-5) scores from Visit 3 to Visit 16.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MDMA-assisted therapy | Experimental | Drug: Midomafetamine HClThree open-label sessions of MDMA-assisted therapy, each scheduled approximately 1 month apart, with initial dose of midomafetamine HCl of 80 or 120 mg and optional supplemental dose half that of initial dose (40 or 60 mg) 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 (15 listed)
- Were previously enrolled in a parent study and (meet one of the following):
- Are considered in good standing with the study site at which they enrolled in a parent study; if, in the opinion of the investigator, therapy team, and Medical Monitor, the participant was compliant with protocol requirements, even if they were unable to complete all study visits.
- Are at least 18 years old
- Are fluent in speaking and reading the predominantly used or recognized language of the study site
- Are able to swallow pills
Key exclusion criteria (9 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] in males and >460 ms in females corrected by Fridericia 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, such as myocardial infarction, cerebrovascular accident, or aneurysm
- Have symptomatic liver disease
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 |
|---|---|---|
| Midomafetamine HClAlso: 3,4-methylenedioxymethamphetamine, MDMA HCl, midomafetamine, MDMAInitial doses per Experimental Session include 80 mg or 120 mg midomafetamine HCl, followed 1.5 to 2 hours later by a supplemental dose unless tolerability issues emerge. For an initial dose of 80 mg, a 40 mg supplemental dose will be used. For an initial dose of 120 mg, a 60 mg supplemental dose will be used. Total amounts of midomafetamine HCl to be administered per Experimental Session range from 80 mg to 180 mg. | Drug | MDMA-assisted therapy |
Primary outcome
Change From Baseline to Visit 16 in PCL-5 Total Score
Time frame: Baseline enrollment to approximately 18 weeks later (Visit 16 occurs 24 to 32 days after Experimental Session 3)
The Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) is a 20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms, derived from the symptoms of PTSD per DSM-5. Participants indicate how much distress they have experienced in the last 2 weeks due to symptoms such as "Repeated, disturbing memories, thoughts, or images of a stressful experience from the past," "Trouble remembering important parts of a stressful experience from the past," and "Feeling irritable or having angry outbursts" on a five-point Likert-type scale (0=Not at all to 4=Extremely). The total severity score can range from 0 to 80 and lower scores indicate less PTSD symptoms.
1 secondary outcome
Change From Baseline to Visit 16 in Sheehan Disability Scale (SDS) Total Score
Time frame: Baseline enrollment to approximately 18 weeks later (Visit 16 occurs 24 to 32 days after Experimental Session 3)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. We will share outcome data appearing in any published reports upon request.
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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.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Midomafetamine HCl in people with PTSD, run by Resilient Pharmaceuticals at 15 sites in 3 countries.
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 15 inclusion and 9 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 6 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 15 sites in United States, Canada, Israel. 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?
Yes. Results are posted in the registry (first posted 29 Nov 2024). 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 16 in PCL-5 Total Score (time frame: Baseline enrollment to approximately 18 weeks later (Visit 16 occurs 24 to 32 days after Experimental Session 3)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jun 2025; AzTrials last refreshed its copy on 6 Nov 2026.