CompletedNCT01689740Updated Jun 6, 2025Results posted

Randomized, Double-blind, Placebo-Controlled Pilot Study of MDMA-assisted Therapy for PTSD

A Phase 2 interventional study of Active Placebo Dose MDMA-assisted therapy (25 mg) and Full Dose MDMA-assisted therapy (125 mg) in Posttraumatic Stress Disorder (PTSD), sponsored by Lykos Therapeutics. Completed at 1 site in Israel. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-06.

Sponsored by Lykos Therapeutics · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 10
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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 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 studied

Posttraumatic Stress Disorder (PTSD)

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Keywords

MDMA
Posttraumatic stress disorder
PTSD
Israel
psychotherapy
midomafetamine

In context

Stress Disorders, Traumatic

1,147 studies on the registry are indexed under Stress Disorders, Traumatic; 108 are open to participants now.

This study's enrollment of 10 is below the median of 60 across 908 interventional studies indexed under Stress Disorders, Traumatic.

Browse Stress Disorders, Traumatic studies →

Lead sponsor

Lykos Therapeutics is the lead sponsor of 28 studies on the registry; 1 is open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 6 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.
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.

Exclusion criteria

Exclusion Criteria:

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 10 participants (actual)

Study arms

Experimental
Lead in: 125 mg MDMA-assisted therapy (Open-Label)
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.
Drug: Open-Label Full Dose MDMA-assisted therapy (125 mg) · Behavioral: Psychotherapy
Placebo comparator
Active placebo dose MDMA-assisted therapy (25 mg)
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.
Drug: Active Placebo Dose MDMA-assisted therapy (25 mg) · Behavioral: Psychotherapy
Experimental
Full dose MDMA-assisted therapy (125 mg)
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.
Drug: Full Dose MDMA-assisted therapy (125 mg) · Behavioral: Psychotherapy

Interventions

DrugActive Placebo Dose MDMA-assisted therapy (25 mg)
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.
Also known as: 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HCl
DrugFull Dose MDMA-assisted therapy (125 mg)
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.
Also known as: 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HCl
DrugOpen-Label Full Dose MDMA-assisted therapy (125 mg)
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.
Also known as: 3,4-methylenedioxymethamphetamine, midomafetamine, MDMA, midomafetamine HCl
BehavioralPsychotherapy
Non-directive psychotherapy will be conducted throughout the study.
Also known as: Manualized MDMA-assisted psychotherapy

What researchers measure

Primary outcomes

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.
Time frame: Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)

Secondary outcomes

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.
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
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.
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
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.
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
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.
Time frame: 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.
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
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.
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
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.
Time frame: 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.
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
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.
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
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.
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
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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: Baseline to 12 months post-final experimental session

Results

Posted Oct 30, 2020

Participant flow

Participants were recruited through printed ads, internet ads, referrals from other psychiatrists, psychotherapists or physicians, through the Israeli Defense Forces (IDF) and through word of mouth.

Stage 1

Participant flow — Stage 1
Milestone	Open-Label: 125 mg MDMA-assisted Therapy	Blinded: Full Dose MDMA-assisted Therapy	Blinded: Active Placebo Dose MDMA-assisted Therapy
Started	2	5	3
Completed	2	5	3
Not completed	0	0	0

Stage 2

Participant flow — Stage 2
Milestone	Open-Label: 125 mg MDMA-assisted Therapy	Blinded: Full Dose MDMA-assisted Therapy	Blinded: Active Placebo Dose MDMA-assisted Therapy
Started	0	0	2
Completed	0	0	2
Not completed	0	0	0

12 Month Follow-Up

Participant flow — 12 Month Follow-Up
Milestone	Open-Label: 125 mg MDMA-assisted Therapy	Blinded: Full Dose MDMA-assisted Therapy	Blinded: Active Placebo Dose MDMA-assisted Therapy
Started	2	5	3
Completed	2	5	2
Not completed	0	0	1

Outcome measures

PrimaryChange 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.

Time frame:: Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)
Reported as:: Mean · score on a scale

Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 1
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 1	-42.0 ± 9.90	-9.0 ± 15.62	-34.6 ± 16.29

SecondaryChange in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 2

Time frame:: Baseline to End of Stage 2
Reported as:: Mean · score on a scale

Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 2
score on a scale	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 2	-23.0 ± 15.56

SecondaryChange 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
Reported as:: Mean · score on a scale

Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to Long-Term Follow-Up
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to Long-Term Follow-Up	-39.0 ± 14.14	-34.5 ± 20.51	-48.8 ± 20.39

SecondaryChange 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.

Time frame:: Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)
Reported as:: Mean · score on a scale

Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to End of Stage 1
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to End of Stage 1	-17.0 ± 2.83	0.3 ± 4.73	-17.0 ± 12.59

SecondaryChange in Beck Depression Inventory (BDI-II) Total Score From Baseline to End of Stage 2

Time frame:: Baseline to End of Stage 2
Reported as:: Mean · score on a scale

Change in Beck Depression Inventory (BDI-II) Total Score From Baseline to End of Stage 2
score on a scale	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy
Change in Beck Depression Inventory (BDI-II) Total Score From Baseline to End of Stage 2	-6.5 ± 4.95

SecondaryChange 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
Reported as:: Mean · score on a scale

Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to Long-Term Follow-Up
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to Long-Term Follow-Up	-17.0 ± 5.66	-3.5 ± 4.95	-18.4 ± 11.10

SecondaryChange 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.

Time frame:: Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)
Reported as:: Mean · score on a scale

Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 1
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 1	15.0 ± 21.21	-2.3 ± 8.74	18.2 ± 11.14

SecondaryChange in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 2

Time frame:: Baseline to End of Stage 2
Reported as:: Mean · score on a scale

Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 2
score on a scale	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy
Change in Global Assessment of Functioning (GAF) Scale From Baseline to End of Stage 2	8.0 ± 9.90

SecondaryChange in Global Assessment of Functioning (GAF) Scale From Baseline to Long-Term Follow-Up

Time frame:: Baseline to 12 months post-final experimental session
Reported as:: Mean · score on a scale

Change in Global Assessment of Functioning (GAF) Scale From Baseline to Long-Term Follow-Up
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Global Assessment of Functioning (GAF) Scale From Baseline to Long-Term Follow-Up	5 ± 7.07	-1.5 ± 0.71	26.6 ± 10.33

SecondaryChange 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.

Time frame:: Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)
Reported as:: Mean · score on a scale

Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 1
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 1	-19.0 ± 5.66	1.3 ± 13.43	-17.4 ± 9.91

SecondaryChange in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 2

Time frame:: Baseline to End of Stage 2
Reported as:: Mean · score on a scale

Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 2
score on a scale	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to End of Stage 2	-11.5 ± 10.61

SecondaryChange 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
Reported as:: Mean · score on a scale

Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to Long-Term Follow-Up
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to Long-Term Follow-Up	-23.0 ± 0	-10 ± 9.90	-20.4 ± 12.70

SecondaryChange 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.

Time frame:: Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)
Reported as:: Mean · score on a scale

Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 1
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 1	-7.5 ± 6.36	1.0 ± 5.29	-1.8 ± 4.44

SecondaryChange in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 2

Time frame:: Baseline to End of Stage 2
Reported as:: Mean · score on a scale

Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 2
score on a scale	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to End of Stage 2	-3.5 ± 3.54

SecondaryChange in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Long-Term Follow-Up

Time frame:: Baseline to 12 months post-final experimental session
Reported as:: Mean · score on a scale

Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Long-Term Follow-Up
score on a scale	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Long-Term Follow-Up	-3.5 ± 3.54	-2.0 ± 4.24	-2.2 ± 5.40

Adverse events

Collected over From baseline to study completion (approximately 18 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Lead In Open-Label: 125 mg MDMA-assisted Therapy	0/2 (0%)	0/2 (0%)	2/2 (100%)
Blinded Full Dose MDMA-assisted Therapy (125 mg) (Stage 1)	0/5 (0%)	0/5 (0%)	4/5 (80%)
Blinded Active Placebo MDMA-assisted Therapy (Stage 1)	0/3 (0%)	0/3 (0%)	1/3 (33.3%)
Open-Label Full Dose MDMA-assisted Therapy (125 mg) (Stage 2)	0/2 (0%)	0/2 (0%)	2/2 (100%)
12 Month Follow-Up: Open-Label Full Dose Lead-In	0/2 (0%)	0/2 (0%)	0/2 (0%)
12 Month Follow-Up: Blinded Full Dose	0/5 (0%)	0/5 (0%)	1/5 (20%)
12 Month Follow-Up: Active Placebo Dose	0/2 (0%)	0/2 (0%)	0/3 (0%)
SRRs: Full Dose	0/5 (0%)	0/5 (0%)	5/5 (100%)
SRRs: Active Placebo	0/3 (0%)	0/3 (0%)	3/3 (100%)

Most frequent other events

Showing 10 of 32

Most frequent other events
Event	Lead In Open-Label: 125 mg MDMA-assisted Therapy	Blinded Full Dose MDMA-assisted Therapy (125 mg) (Stage 1)	Blinded Active Placebo MDMA-assisted Therapy (Stage 1)	Open-Label Full Dose MDMA-assisted Therapy (125 mg) (Stage 2)	12 Month Follow-Up: Open-Label Full Dose Lead-In	12 Month Follow-Up: Blinded Full Dose	12 Month Follow-Up: Active Placebo Dose	SRRs: Full Dose	SRRs: Active Placebo
AnxietyPsychiatric disorders	1/2	4/5	0/3	0/2	0/2	0/5	0/3	5/5	1/3
InsomniaPsychiatric disorders	1/2	0/5	0/3	0/2	0/2	0/5	0/3	5/5	1/3
FatigueGeneral disorders	0/2	0/5	0/3	0/2	0/2	0/5	0/3	5/5	2/3
HeadacheNervous system disorders	0/2	1/5	0/3	0/2	0/2	0/5	0/3	4/5	0/3
Low moodGeneral disorders	0/2	0/5	0/3	0/2	0/2	0/5	0/3	3/5	2/3
Muscle tensionGeneral disorders	0/2	0/5	0/3	0/2	0/2	0/5	0/3	2/5	2/3
RestlessnessGeneral disorders	0/2	0/5	0/3	0/2	0/2	0/5	0/3	3/5	2/3
Need more sleepGeneral disorders	0/2	0/5	0/3	0/2	0/2	0/5	0/3	3/5	1/3
PyrexiaGeneral disorders	1/2	1/5	0/3	0/2	0/2	0/5	0/3	0/5	0/3
AsthmaRespiratory, thoracic and mediastinal disorders	1/2	0/5	0/3	0/2	0/2	0/5	0/3	0/5	0/3

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Total
Mean	40.5 ± 19.72	35.1 ± 10.21	38.5 ± 8.68	37.2 ± 10.57

Sex: Female, Male
Sex: Female, Male(Participants)	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Total
Female	1	3	0	4
Male	1	2	3	6

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Total
Hispanic or Latino	0	0	0	0
Not Hispanic or Latino	2	5	3	10
Unknown or Not Reported	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Full Dose MDMA (125 mg) and Psychotherapy	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Total
Ethnicity — White/Caucasian	2	5	2	9
Ethnicity — Other	0	0	1	1

Study locations

1 site

Beer Yaakov Hospital
Be'er Ya'aqov, 70350, Israel

References and documents

Publications

Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995 Jan;8(1):75-90. doi: 10.1007/BF02105408. PubMed 7712061 ↗
Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020 Aug;237(8):2485-2497. doi: 10.1007/s00213-020-05548-2. Epub 2020 Jun 4. PubMed 32500209 ↗
Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry. 2019 Sep 12;10:650. doi: 10.3389/fpsyt.2019.00650. eCollection 2019. PubMed 31572236 ↗
Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7. PubMed 31065731 ↗

Study documents

Study protocol · Mar 30, 2015
Statistical analysis plan · May 31, 2016
Informed consent form · Jul 22, 2016

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 6, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01689740
Lead sponsor: Lykos Therapeutics
Responsible party: Sponsor
First posted: Sep 21, 2012
Start date: Jan 17, 2013
Primary completion: Apr 7, 2016
Completion: Jul 16, 2017
Results posted: Oct 30, 2020
Last update: Jun 6, 2025

Study contacts

Moshe Kotler

principal investigator · Beer Yaakov Hospital

View the source record on ClinicalTrials.gov ↗

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