Posttraumatic Stress DisorderPhase 3NCT03537014
A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP1)
A Phase 3 study testing Therapy and midomafetamine HCl in people with Posttraumatic Stress Disorder, 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 in people with at least severe PTSD. The main question it aims to answer is: Do three sessions of MDMA-assisted therapy reduce PTSD symptoms? Researchers will compare three sessions of MDMA-assisted therapy with an initial dose… 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?
- Therapy and midomafetamine HCl
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 15 sitesin 3 countries
- Study dates
- 21 Nov 2018to 21 Aug 2020
- 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
- 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
- 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
Show all 10Show fewer
- 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
- 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
- At baseline, meet DSM-5 criteria for current 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] in males and >460 ms in females 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, such as myocardial infarction, cerebrovascular accident, or aneurysm
- Have symptomatic liver disease
Show all 11Show fewer
- 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
- Have an active illicit or prescription drug use disorder
- 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; or have previously participated in a MAPS-sponsored MDMA clinical trial.
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
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
New York Private Practice
New York, New York, 10024
New School Research LLT
North Hollywood, California, 91601
San Francisco Insight and Integration Center
San Francisco, California, 94114
University of California San Francisco
San Francisco, California, 94122
Canada2 sites
Dr. Simon Amar, Inc.
Montreal, Quebec, H2W1Y9
Providence Health Center
Vancouver, British Columbia, V5R 5H3
Israel2 sites
Assaf Harofeh Research Fund
Be’er Ya‘aqov
Sheba Fund for Health Services and Research
Tel HaShomer
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy 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 with at least severe PTSD.
The main question it aims to answer is: Do three sessions of MDMA-assisted therapy reduce PTSD symptoms?
Researchers will compare three sessions of MDMA-assisted therapy with an initial dose of 80 to 120 mg to three sessions of placebo with therapy.
Participants will undergo three preparatory sessions without any study drug, followed by three MDMA-assisted therapy or placebo with therapy sessions. Each medication session will be followed by three integrative therapy sessions without study drug.
Read the detailed description
This multi-site, double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with at least severe PTSD. The study will be conducted in N ≈ 100 participants. Participants will be randomized to one of two groups at a 1:1 ratio. An initial dose of midomafetamine HCl or placebo, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized therapy in three monthly Experimental Sessions. 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. Initial doses per Experimental Session include 80 mg or 120 mg of midomafetamine HCl or placebo followed 1.5 to 2 hours later by a supplemental half-dose (40 or 60 mg). Total amounts of midomafetamine HCl to be administered per Experimental Session range from 80 mg to 180 mg.
The primary endpoint is change from baseline in Clinician Administered PTSD Scale for DSM-V (CAPS-5) to 18 weeks post-Baseline. Drug safety will be assessed by measuring blood pressure, heart rate and body temperature during Experimental Sessions, collecting adverse events and measuring suicidal thoughts or behaviors with the Columbia Suicide Severity Rating Scale (adapted C-SSRS).
- Conditions
- Posttraumatic Stress Disorder
- Being tested
- Therapy, midomafetamine HCl, Placebo
- 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.
TherapyBehavioural
Also called Manualized therapy
Non-directive therapy performed by therapist team
midomafetamine HClDrug
Also called 3,4-methylenedioxymethamphetamine, MDMA, midomafetamine, MDMA HCl
Administration of 80 to 120 mg midomafetamine HCl, followed by a supplemental dose 1.5 to 2 hrs later of 40 or 60 mg midomafetamine HCl, respectively, during three experimental sessions
PlaceboDrug
Also called Inactive placebo
Administration of placebo during three experimental sessions
| Study group | Role | What they receive |
|---|---|---|
| MDMA-assisted therapy | Experimental | Administration of 80 or 120 mg midomafetamine HCl with a supplemental dose 1.5 to 2 hours later of 40 or 60 mg midomafetamine HCl, respectively, in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart. Receives: Behavioral: Therapy; Drug: midomafetamine HCl |
| Placebo with therapy | Placebo comparator | Administration of inactive placebo in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart Receives: Behavioral: Therapy; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5)
The CAPS-5 is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.
Measured: Baseline to 18 weeks post enrollment confirmation
Secondary outcomes (1)
Change From Baseline to Primary Endpoint in Sheehan Disability Scale (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 confirmation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start21 Nov 2018
- Primary completion11 Aug 2020
- Study completion21 Aug 2020
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 (2)Papers the sponsor has linked to this study.
- Other trials for Posttraumatic Stress DisorderStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, between-group comparison of change in PTSD symptoms
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Resilient Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Casey Paleos, MD, Principal investigator, Affective CareBessel van der Kolk, MD, Principal investigator, Trauma Research FoundationEmma Hapke, MD, Principal investigator, Dr. Simon Amar, Inc.Revital Amiaz, MD, Principal investigator, The Chaim Sheba Medical Center, Tel Hashomer HospitalMichael Bogenschutz, MD, Principal investigator, New York University/Langone Medical Center/Bellevue HospitalRandall Brown, MD, PhD, Principal investigator, University of Wisconsin, MadisonSylvestre Quevedo, MD, Principal investigator, San Francisco Insight and Integration CenterJosh Woolley, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537014
- Sponsor's protocol ID
- MAPP1
- Status last verified
- May 2025
- First submitted
- 14 May 2018
- 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.
Publications
Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10.
PubMed 33972795van der Kolk BA, Wang JB, Yehuda R, Bedrosian L, Coker AR, Harrison C, Mithoefer M, Yazar-Klosinki B, Emerson A, Doblin R. Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS One. 2024 Jan 10;19(1):e0295926. doi: 10.1371/journal.pone.0295926. eCollection 2024.
PubMed 38198456
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 Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT03537014
- Acronym / sponsor ID
- MAPP1
- Conditions
- Posttraumatic Stress Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Resilient PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2018 (actual)
- Primary completion
- 11 Aug 2020 (actual)
- Study completion
- 21 Aug 2020 (actual)
- First posted
- 25 May 2018 (actual)
- Results
- Posted 16 Sep 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 with at least severe PTSD.
The main question it aims to answer is: Do three sessions of MDMA-assisted therapy reduce PTSD symptoms?
Researchers will compare three sessions of MDMA-assisted therapy with an initial dose of 80 to 120 mg to three sessions of placebo with therapy.
Participants will undergo three preparatory sessions without any study drug, followed by three MDMA-assisted therapy or placebo with therapy sessions. Each medication session will be followed by three integrative therapy sessions without study drug.
Detailed description
This multi-site, double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with at least severe PTSD. The study will be conducted in N ≈ 100 participants. Participants will be randomized to one of two groups at a 1:1 ratio. An initial dose of midomafetamine HCl or placebo, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized therapy in three monthly Experimental Sessions. 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. Initial doses per Experimental Session include 80 mg or 120 mg of midomafetamine HCl or placebo followed 1.5 to 2 hours later by a supplemental half-dose (40 or 60 mg). Total amounts of midomafetamine HCl to be administered per Experimental Session range from 80 mg to 180 mg.
The primary endpoint is change from baseline in Clinician Administered PTSD Scale for DSM-V (CAPS-5) to 18 weeks post-Baseline. Drug safety will be assessed by measuring blood pressure, heart rate and body temperature during Experimental Sessions, collecting adverse events and measuring suicidal thoughts or behaviors with the Columbia Suicide Severity Rating Scale (adapted C-SSRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, between-group comparison of change in PTSD symptoms
| Arm | Type | Receives |
|---|---|---|
| MDMA-assisted therapy | Experimental | Behavioral: Therapy, Drug: midomafetamine HClAdministration of 80 or 120 mg midomafetamine HCl with a supplemental dose 1.5 to 2 hours later of 40 or 60 mg midomafetamine HCl, respectively, in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart. |
| Placebo with therapy | Placebo comparator | Behavioral: Therapy, Drug: PlaceboAdministration of inactive placebo in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- 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.
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] in males and >460 ms in females 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, such as myocardial infarction, cerebrovascular accident, or aneurysm
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 |
|---|---|---|
| TherapyAlso: Manualized therapyNon-directive therapy performed by therapist team | Behavioural | MDMA-assisted therapy, Placebo with therapy |
| midomafetamine HClAlso: 3,4-methylenedioxymethamphetamine, MDMA, midomafetamine, MDMA HClAdministration of 80 to 120 mg midomafetamine HCl, followed by a supplemental dose 1.5 to 2 hrs later of 40 or 60 mg midomafetamine HCl, respectively, during three experimental sessions | Drug | MDMA-assisted therapy |
| PlaceboAlso: Inactive placeboAdministration of placebo during three experimental sessions | Drug | Placebo with therapy |
Primary outcome
Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5)
Time frame: Baseline to 18 weeks post enrollment confirmation
The CAPS-5 is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.
1 secondary outcome
Change From Baseline to Primary Endpoint in Sheehan Disability Scale (SDS) Total Score
Time frame: Baseline to 18 weeks post enrollment confirmation
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.
- Results publication: PubMed 33972795Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10.
- Derived from this study: PubMed 38198456van der Kolk BA, Wang JB, Yehuda R, Bedrosian L, Coker AR, Harrison C, Mithoefer M, Yazar-Klosinki B, Emerson A, Doblin R. Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS One. 2024 Jan 10;19(1):e0295926. doi: 10.1371/journal.pone.0295926. eCollection 2024.
- 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.
Casey Paleos, MD principal investigator
Affective Care
Bessel van der Kolk, MD principal investigator
Trauma Research Foundation
Emma Hapke, MD principal investigator
Dr. Simon Amar, Inc.
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 Therapy and midomafetamine HCl in people with Posttraumatic Stress Disorder, 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 10 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 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. Some participants in this study may receive a placebo. 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 16 Sep 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 Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5) (time frame: Baseline to 18 weeks post enrollment confirmation). 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 NCT03537014, which also lists 2 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 6 Jun 2025.