Posttraumatic Stress Disorder (PTSD)Phase 2NCT01689740
Randomized, Double-blind, Placebo-Controlled Pilot Study of MDMA-assisted Therapy for PTSD
A Phase 2 study testing Full Dose MDMA-assisted therapy (125 mg), Open-Label Full Dose MDMA-assisted therapy (125 mg) and Psychotherapy in people with Posttraumatic Stress Disorder (PTSD), run by Resilient Pharmaceuticals at 1 site in Israel.
Trial summary
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with chronic, treatment-resistant PTSD. The main question it aims to answer is: Is there a reduction in PTSD symptoms in people given a low dose of MDMA with therapy versus a high dose of MDMA with therapy? Researchers… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Posttraumatic Stress Disorder (PTSD)
- What is being tested?
- Full Dose MDMA-assisted therapy (125 mg), Open-Label Full Dose MDMA-assisted therapy (125 mg) and Psychotherapy
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteIsrael
- Study dates
- 17 Jan 2013to 16 Jul 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 with a duration of 6 months or longer.
- Have a CAPS score showing moderate to severe symptoms.
- Had at least one unsuccessful attempt at treatment for PTSD, either with talk therapy or with drugs, or stopped treatment because of inability to tolerate psychotherapy or drug therapy.
- Are at least 18 years old.
- Generally healthy.
- Must sign a medical release for the investigators to communicate directly with their therapist and doctors.
Show all 15Show fewer
- Are willing to refrain from taking any psychiatric medications during the study period.
- Agree that, one week before the MDMA session, will refrain from taking all below unless with prior approval of research team: herbal supplements, nonprescription medications (with the exception of nonsteroidal anti-inflammatory drugs or acetaminophen, any prescription medications, with the exception of birth control pills, thyroid hormone, or other medications;
- Are willing to follow restrictions and guidelines concerning consumption of food, beverages. and nicotine the night before and just prior to each experimental session.
- Are willing to remain overnight at the study site.
- Are willing to be contacted via telephone for all necessary telephone contacts.
- Must have a negative pregnancy test if able to bear children, and agree to use an effective form of birth control.
- Agree not to participate in any other clinical trial for the duration of this clinical trial, including the follow-up period.
- Are proficient in speaking and reading Hebrew.
- Agree to have all psychotherapy sessions recorded to audio/video.
Who cannot join
- Are pregnant or nursing, or if they can have children and are not practicing an effective means of birth control.
- Weigh less than 48 kg.
- Are abusing illegal drugs.
- Have used "Ecstasy" (material represented as containing MDMA) more than five times 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.
About this study
Official title: A Randomized, Double-Blind, Active Placebo-Controlled Phase 2 Pilot Study of MDMA-assisted Psychotherapy in People With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with chronic, treatment-resistant PTSD.
The main question it aims to answer is: Is there a reduction in PTSD symptoms in people given a low dose of MDMA with therapy versus a high dose of MDMA with therapy?
Read more
Researchers will compare two sessions of MDMA-assisted therapy with either 25 mg of MDMA HCl or 125 mg of MDMA HCl in Stage 1.
Participants will undergo preparatory therapy sessions without any study drug, followed by two sessions of MDMA-assisted therapy, each followed by integrative therapy sessions without study drug. Participants who received 25 mg during Stage 1 will be given the option to enroll in Stage 2 and complete two additional open-label MDMA-assisted therapy sessions with the full dose of 125 mg MDMA.
Read the detailed description
This randomized, double-blind, active placebo-controlled Phase 2 pilot study investigated the safety and efficacy of MDMA-assisted psychotherapy in 10 people with chronic, treatment-resistant posttraumatic stress disorder (PTSD), comparing the effects of low and full dose MDMA as an adjunct to psychotherapy. The first two subjects were enrolled in the open label full dose lead-in with 125 mg of midomafetamine HCl, followed by a supplemental half-dose of 62.5 mg after 1.5 to 2.5 hours. The remaining eight subjects enrolled in Stage 1 of the study and received either an active placebo dose (low dose of 25 mg midomafetamine HCl with a supplemental half-dose of 12.5 mg) or a fully active dose (125 mg midomafetamine HCl with a supplemental half-dose of 62.5 mg) during two experimental psychotherapy session, each lasting six to eight hours and scheduled three to five weeks apart.
Upon enrollment, subjects met with their therapist team for three preparatory sessions. After each MDMA-assisted psychotherapy session, subjects met with their therapist team for integrative psychotherapy sessions.
The extent of PTSD symptoms was assessed at baseline and two months after the second experimental session using the Clinician Administered PTSD Scale (CAPS) (Blake et al., 1995). Safety measures, vital signs, and a measurement of psychological distress was assessed during all experimental sessions. Blood pressure and heart rate were assessed periodically during each experimental session.
Subjects who enrolled in Stage 1 and received the active placebo had the opportunity to enroll in Stage 2 of the study and complete open-label experimental sessions with the fully active dose of midomafetamine HCl (125 mg and 62.5 mg supplemental) on the same schedule as Stage 1.
- Conditions
- Posttraumatic Stress Disorder (PTSD)
- Being tested
- Active Placebo Dose MDMA-assisted therapy (25 mg), Full Dose MDMA-assisted therapy (125 mg), Open-Label Full Dose MDMA-assisted therapy (125 mg), Psychotherapy
- Keywords
- MDMA, Posttraumatic stress disorder, PTSD, Israel, psychotherapy, 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.
Active Placebo Dose MDMA-assisted therapy (25 mg)Drug
Also called 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HCl
Initial dose of 25 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 12.5 mg 1.5 to 2.5 hours later.
Full Dose MDMA-assisted therapy (125 mg)Drug
Also called 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HCl
Initial dose of 125 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg 1.5 to 2.5 hours later.
Open-Label Full Dose MDMA-assisted therapy (125 mg)Drug
Also called 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HCl
Initial dose of 125 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg 1.5 to 2.5 hours later.
PsychotherapyBehavioural
Also called Manualized MDMA-assisted psychotherapy
Non-directive psychotherapy will be conducted throughout the study.
| Study group | Role | What they receive |
|---|---|---|
| Lead in: 125 mg MDMA-assisted therapy (Open-Label) | Experimental | Participants receive open-label MDMA with an initial dose of 125 mg midomafetamine HCl, possibly followed by a supplemental dose of 62.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart. Receives: Drug: Open-Label Full Dose MDMA-assisted therapy (125 mg); Behavioral: Psychotherapy |
| Active placebo dose MDMA-assisted therapy (25 mg) | Placebo comparator | Participants receive initial dose of 25 mg midomafetamine HCl, possibly followed by a supplemental dose of 12.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart. Receives: Drug: Active Placebo Dose MDMA-assisted therapy (25 mg); Behavioral: Psychotherapy |
| Full dose MDMA-assisted therapy (125 mg) | Experimental | Participants receive initial dose of 125 mg midomafetamine HCl, possibly followed by a supplemental dose of 62.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart. Receives: Drug: Full Dose MDMA-assisted therapy (125 mg); Behavioral: Psychotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 1
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. 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 1-Month Post Experimental Session 2 (End of Stage 1)
Secondary outcomes (14)
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 2
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. 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 End of Stage 2
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to Long-Term Follow-Up
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. 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 12 months post-final experimental session
Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to End of Stage 1
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 BDI-II is scored by summing the ratings for the 21 items. Each item is rated on a 4-point scale ranging from 0 to 3. The maximum total score is 63.
Measured: Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)
Change in Beck Depression Inventory (BDI-II) Total Score From Baseline to End of Stage 2
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 BDI-II is scored by summing the ratings for the 21 items. Each item is rated on a 4-point scale ranging from 0 to 3. The maximum total score is 63.
Measured: Baseline to End of Stage 2
Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to Long-Term Follow-Up
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 BDI-II is scored by summing the ratings for the 21 items. Each item is rated on a 4-point scale ranging from 0 to 3. The maximum total score is 63.
Measured: Baseline to 12 month post-final experimental session
Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 1
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 to 1-Month Post 2nd Experimental Session (End of Stage 1)
Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 2
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 to End of Stage 2
Change in Global Assessment of Functioning (GAF) Scale From Baseline to Long-Term Follow-Up
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 to 12 months post-final experimental session
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 1
The Posttraumatic Stress Diagnostic Scale (PDS) is a 49-item self-report instrument designed to aid in the diagnosis of PTSD. Responses to 17 symptom items are made on a 4 point scale ranging from 0 (not at all) to 3 (five or more times per week). The symptom items are summed to calculate the symptom severity score which ranges from 0 to 51, with higher scores indicating more severe PTSD symptoms.
Measured: Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 2
The Posttraumatic Stress Diagnostic Scale (PDS) is a 49-item self-report instrument designed to aid in the diagnosis of PTSD. Responses to 17 symptom items are made on a 4 point scale ranging from 0 (not at all) to 3 (five or more times per week). The symptom items are summed to calculate the symptom severity score which ranges from 0 to 51, with higher scores indicating more severe PTSD symptoms.
Measured: Baseline to End of Stage 2
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to Long-Term Follow-Up
The Posttraumatic Stress Diagnostic Scale (PDS) is a 49-item self-report instrument designed to aid in the diagnosis of PTSD. Responses to 17 symptom items are made on a 4 point scale ranging from 0 (not at all) to 3 (five or more times per week). The symptom items are summed to calculate the symptom severity score which ranges from 0 to 51, with higher scores indicating more severe PTSD symptoms.
Measured: Baseline to 12 months post-final experimental session
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 1
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 to 1-Month Post 2nd Experimental Session (End of Stage 1)
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 2
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 to End of Stage 2
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Long-Term Follow-Up
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 to 12 months post-final experimental session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2012 (estimated)
- Study start17 Jan 2013
- Primary completion7 Apr 2016
- Study completion16 Jul 2017
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 (4)Papers the sponsor has linked to this study.
- Other trials for Posttraumatic Stress Disorder (PTSD)Studies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Resilient Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Moshe Kotler, Principal investigator, Beer Yaakov Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01689740
- Sponsor's protocol ID
- MP-9
- Status last verified
- May 2025
- First submitted
- 7 Sep 2012
- Last updated
- 6 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
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 7712061Jerome 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 32500209Feduccia 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 31572236Mithoefer 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
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, Active Placebo-Controlled Phase 2 Pilot Study of MDMA-assisted Psychotherapy in People With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)
- ClinicalTrials.gov ID
- NCT01689740
- Acronym / sponsor ID
- MP-9
- Conditions
- Posttraumatic Stress Disorder (PTSD)
- Keywords
- MDMA, Posttraumatic stress disorder, PTSD, Israel, psychotherapy, midomafetamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Resilient PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 Jan 2013 (actual)
- Primary completion
- 7 Apr 2016 (actual)
- Study completion
- 16 Jul 2017 (actual)
- First posted
- 21 Sep 2012 (estimated)
- Results
- Posted 30 Oct 2020
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 chronic, treatment-resistant PTSD.
The main question it aims to answer is: Is there a reduction in PTSD symptoms in people given a low dose of MDMA with therapy versus a high dose of MDMA with therapy?
Researchers will compare two sessions of MDMA-assisted therapy with either 25 mg of MDMA HCl or 125 mg of MDMA HCl in Stage 1.
Participants will undergo preparatory therapy sessions without any study drug, followed by two sessions of MDMA-assisted therapy, each followed by integrative therapy sessions without study drug. Participants who received 25 mg during Stage 1 will be given the option to enroll in Stage 2 and complete two additional open-label MDMA-assisted therapy sessions with the full dose of 125 mg MDMA.
Detailed description
This randomized, double-blind, active placebo-controlled Phase 2 pilot study investigated the safety and efficacy of MDMA-assisted psychotherapy in 10 people with chronic, treatment-resistant posttraumatic stress disorder (PTSD), comparing the effects of low and full dose MDMA as an adjunct to psychotherapy. The first two subjects were enrolled in the open label full dose lead-in with 125 mg of midomafetamine HCl, followed by a supplemental half-dose of 62.5 mg after 1.5 to 2.5 hours. The remaining eight subjects enrolled in Stage 1 of the study and received either an active placebo dose (low dose of 25 mg midomafetamine HCl with a supplemental half-dose of 12.5 mg) or a fully active dose (125 mg midomafetamine HCl with a supplemental half-dose of 62.5 mg) during two experimental psychotherapy session, each lasting six to eight hours and scheduled three to five weeks apart.
Upon enrollment, subjects met with their therapist team for three preparatory sessions. After each MDMA-assisted psychotherapy session, subjects met with their therapist team for integrative psychotherapy sessions.
The extent of PTSD symptoms was assessed at baseline and two months after the second experimental session using the Clinician Administered PTSD Scale (CAPS) (Blake et al., 1995). Safety measures, vital signs, and a measurement of psychological distress was assessed during all experimental sessions. Blood pressure and heart rate were assessed periodically during each experimental session.
Subjects who enrolled in Stage 1 and received the active placebo had the opportunity to enroll in Stage 2 of the study and complete open-label experimental sessions with the fully active dose of midomafetamine HCl (125 mg and 62.5 mg supplemental) on the same schedule as Stage 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lead in: 125 mg MDMA-assisted therapy (Open-Label) | Experimental | Drug: Open-Label Full Dose MDMA-assisted therapy (125 mg), Behavioral: PsychotherapyParticipants receive open-label MDMA with an initial dose of 125 mg midomafetamine HCl, possibly followed by a supplemental dose of 62.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart. |
| Active placebo dose MDMA-assisted therapy (25 mg) | Placebo comparator | Drug: Active Placebo Dose MDMA-assisted therapy (25 mg), Behavioral: PsychotherapyParticipants receive initial dose of 25 mg midomafetamine HCl, possibly followed by a supplemental dose of 12.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart. |
| Full dose MDMA-assisted therapy (125 mg) | Experimental | Drug: Full Dose MDMA-assisted therapy (125 mg), Behavioral: PsychotherapyParticipants receive initial dose of 125 mg midomafetamine HCl, possibly followed by a supplemental dose of 62.5 mg, during two psychotherapy 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 (15 listed)
- Diagnosed with chronic PTSD with a duration of 6 months or longer.
- Have a CAPS score showing moderate to severe symptoms.
- Had at least one unsuccessful attempt at treatment for PTSD, either with talk therapy or with drugs, or stopped treatment because of inability to tolerate psychotherapy or drug therapy.
- Are at least 18 years old.
- Generally healthy.
Key exclusion criteria (7 listed)
- Are pregnant or nursing, or if they can have children and are not practicing an effective means of birth control.
- Weigh less than 48 kg.
- Are abusing illegal drugs.
- Have used "Ecstasy" (material represented as containing MDMA) more than five times or at least once within 6 months of the MDMA session.
- Are unable to give adequate informed consent.
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 |
|---|---|---|
| Active Placebo Dose MDMA-assisted therapy (25 mg)Also: 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HClInitial dose of 25 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 12.5 mg 1.5 to 2.5 hours later. | Drug | Active placebo dose MDMA-assisted therapy (25 mg) |
| Full Dose MDMA-assisted therapy (125 mg)Also: 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HClInitial dose of 125 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg 1.5 to 2.5 hours later. | Drug | Full dose MDMA-assisted therapy (125 mg) |
| Open-Label Full Dose MDMA-assisted therapy (125 mg)Also: 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HClInitial dose of 125 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg 1.5 to 2.5 hours later. | Drug | Lead in: 125 mg MDMA-assisted therapy (Open-Label) |
| PsychotherapyAlso: Manualized MDMA-assisted psychotherapyNon-directive psychotherapy will be conducted throughout the study. | Behavioural | Active placebo dose MDMA-assisted therapy (25 mg), Full dose MDMA-assisted therapy (125 mg), Lead in: 125 mg MDMA-assisted therapy (Open-Label) |
Primary outcome
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 1
Time frame: Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)
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. 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.
14 secondary outcomes
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 2
Time frame: Baseline to End of Stage 2
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to Long-Term Follow-Up
Time frame: Baseline to 12 months post-final experimental session
Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to End of Stage 1
Time frame: Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)
Change in Beck Depression Inventory (BDI-II) Total Score From Baseline to End of Stage 2
Time frame: Baseline to End of Stage 2
Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to Long-Term Follow-Up
Time frame: Baseline to 12 month post-final experimental session
Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 1
Time frame: Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)
Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 2
Time frame: Baseline to End of Stage 2
Change in Global Assessment of Functioning (GAF) Scale From Baseline to Long-Term Follow-Up
Time frame: Baseline to 12 months post-final experimental session
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 1
Time frame: Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 2
Time frame: Baseline to End of Stage 2
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to Long-Term Follow-Up
Time frame: Baseline to 12 months post-final experimental session
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 1
Time frame: Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 2
Time frame: Baseline to End of Stage 2
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Long-Term Follow-Up
Time frame: Baseline to 12 months post-final experimental session
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.
- Background: PubMed 7712061Blake 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.
- Derived from this study: PubMed 32500209Jerome 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.
- Derived from this study: PubMed 31572236Feduccia 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.
- Derived from this study: PubMed 31065731Mithoefer 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.
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Recruiting
Recovering Sleep After Trauma
Post-traumatic Stress Disorder
Recruiting
Evaluating Evidenced Based Options for PTSD Treatment
PTSD - Post Traumatic Stress Disorder
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.
Moshe Kotler principal investigator
Beer Yaakov Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Full Dose MDMA-assisted therapy (125 mg), Open-Label Full Dose MDMA-assisted therapy (125 mg) and Psychotherapy in people with Posttraumatic Stress Disorder (PTSD), run by Resilient Pharmaceuticals at 1 site in Israel.
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 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 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 1 site in 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 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 30 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 Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 1 (time frame: Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)). 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 NCT01689740, which also lists 4 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.