Randomized, Double-blind, Placebo-Controlled Pilot Study... | NCT01689740

NCT01689740

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	Drug: Full Dose MDMA-assisted therapy (125 mg) Behavioral: Psychotherapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Active Placebo Dose MDMA-assisted therapy (25 mg)	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

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:

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.

Contacts/Locations Module

Name	Affiliation	Role
Moshe Kotler	Beer Yaakov Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Beer Yaakov Hospital		Be’er Ya‘aqov		70350	Israel

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
7712061	Background	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.
32500209	Derived	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.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Open-Label: 125 mg MDMA-assisted Therapy	Open label: Participants receive initial dose of 125 mg midomafetamine HCl possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
FG001	Blinded: Full Dose MDMA-assisted Therapy

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 30, 2015	Oct 9, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Active placebo dose MDMA-assisted therapy (25 mg)

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Participants receive open MDMA with an initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
BG001	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
BG002	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial doses of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0002 BG0015 BG0023 BG00310

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00040.5± 19.72 BG00135.1± 10.21 BG00238.5± 8.68 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001 BG0013 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Ethnicity

Title	Measurements
White/Caucasian	BG0002 BG0015 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Intent-to-Treat (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Units	Counts
Participants	OG0002 OG0013 OG0025

Title

Denominators

Categories

Title	Measurements
	OG000-42.0± 9.90 OG001-9.0± 15.62 OG002-34.6± 16.29

Secondary

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

Posted

Mean

Standard Deviation

score on a scale

Baseline to End of Stage 2

ID	Title	Description
OG000	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy	Stage 1: 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. Stage 2: Participants crossover to receive two open-label sessions of MDMA-assisted therapy with 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg.

Units	Counts
Participants	OG000

Secondary

Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to Long-Term Follow-Up

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 12 months post-final experimental session

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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.

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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

Posted

Mean

Standard Deviation

score on a scale

Baseline to End of Stage 2

ID	Title	Description
OG000	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy	Stage 1: 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. Stage 2: Participants crossover to receive two open-label sessions of MDMA-assisted therapy with 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg.

Units	Counts
Participants	OG000

Secondary

Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to Long-Term Follow-Up

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 12 month post-final experimental session

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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.

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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

Posted

Mean

Standard Deviation

score on a scale

Baseline to End of Stage 2

ID	Title	Description
OG000	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy	Stage 1: 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. Stage 2: Participants crossover to receive two open-label sessions of MDMA-assisted therapy with 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg.

Units	Counts
Participants	OG000

Secondary

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

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 12 months post-final experimental session

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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.

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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

Posted

Mean

Standard Deviation

score on a scale

Baseline to End of Stage 2

ID	Title	Description
OG000	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy	Stage 1: 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. Stage 2: Participants crossover to receive two open-label sessions of MDMA-assisted therapy with 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg.

Units	Counts
Participants	OG000

Secondary

Change in Posttraumatic Stress Diagnostic Scale (PDS) Symptom Severity Score From Baseline to Long-Term Follow-Up

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 12 months post-final experimental session

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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.

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 1-Month Post 2nd Experimental Session (End of Stage 1)

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Secondary

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

Crossover set

Posted

Mean

Standard Deviation

score on a scale

Baseline to End of Stage 2

ID	Title	Description
OG000	Stage 2 Open-Label Crossover 125 mg MDMA-assisted Therapy	Stage 1: 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. Stage 2: Participants crossover to receive two open-label sessions of MDMA-assisted therapy with 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg.

Units	Counts
Participants	OG000

Secondary

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

Intent-to-Treat set (ITT)

Posted

Mean

Standard Deviation

score on a scale

Baseline to 12 months post-final experimental session

ID	Title	Description
OG000	Lead in: 125 mg MDMA (Open Label) and Psychotherapy	Open label: Participants receive open-label MDMA with initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions.
OG001	Active Placebo Dose MDMA (25 mg) and Psychotherapy	Participants receive initial dose of 25 mg MDMA possibly followed by a supplemental dose of 12.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.
OG002	Full Dose MDMA (125 mg) and Psychotherapy	Participants receive initial dose of 125 mg MDMA possibly followed by a supplemental dose of 62.5 mg during two psychotherapy sessions scheduled 3-5 weeks apart.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lead In Open-Label: 125 mg MDMA-assisted Therapy	Participants receive initial dose of 125 mg midomafetamine HCl possibly followed by a supplemental dose of 62.5 mg during two therapy sessions.	2	2	2	2
EG001	Blinded Full Dose MDMA-assisted Therapy (125 mg) (Stage 1)	Participants receive initial dose of 125 mg midomafetamine HCl possibly followed by a supplemental dose of 62.5 mg during two therapy sessions scheduled 3-5 weeks apart.	5	5	4	5
EG002	Blinded Active Placebo MDMA-assisted Therapy (Stage 1)	Participants receive initial dose of 25 mg midomafetamine HCl possibly followed by a supplemental dose of 12.5 mg during two therapy sessions scheduled 3-5 weeks apart.	3	3	1	3
EG003	Open-Label Full Dose MDMA-assisted Therapy (125 mg) (Stage 2)	Stage 1 activate placebo dose participants receive initial dose of 125 mg midomafetamine HCl possibly followed by a supplemental dose of 62.5 mg during two therapy sessions scheduled 3-5 weeks apart.	2	2	2	2
EG004	12 Month Follow-Up: Open-Label Full Dose Lead-In	Includes Adverse Events that start on or after the day after end of Stage 1 for subject who did not cross over to Stage 2 or end of Stage 2 through the end of the study.	2	2	0	2
EG005	12 Month Follow-Up: Blinded Full Dose	Includes Adverse Events that start on or after the day after end of Stage 1 for subject who did not cross over to Stage 2 or end of Stage 2 through the end of the study.	5	5	1	5
EG006	12 Month Follow-Up: Active Placebo Dose	Includes Adverse Events that start on or after the day after end of Stage 1 for subject who did not cross over to Stage 2 or end of Stage 2 through the end of the study.	2	2	0	3
EG007	SRRs: Full Dose	Spontaneously reported reactions (SRRs) during blinded experimental sessions and 7 days after.	5	5	5	5
EG008	SRRs: Active Placebo	Spontaneously reported reactions (SRRs) during blinded experimental sessions and 7 days after.	3	3	3	3

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0000 affected2 at risk EG0011 affected5 at risk EG0020 affected3 at risk EG0030 affected2 at risk EG0040 affected2 at risk EG0050 affected5 at risk EG0060 affected3 at risk EG0072 affected5 at risk EG0080 affected3 at risk
Intestinal obstruction	Gastrointestinal disorders	Non-systematic Assessment	EG0000 affected2 at risk EG0011 affected5 at risk EG0020 affected3 at risk EG003
Pyrexia	General disorders	Non-systematic Assessment	EG0001 affected2 at risk EG0011 affected5 at risk EG0020 affected3 at risk EG003
Influenza	Infections and infestations	Non-systematic Assessment	EG0000 affected2 at risk EG0011 affected5 at risk EG0021 affected3 at risk EG003
Headache	Nervous system disorders	Non-systematic Assessment	EG0000 affected2 at risk EG0011 affected5 at risk EG0020 affected3 at risk EG003
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 affected2 at risk EG0012 affected5 at risk EG0020 affected3 at risk EG003
Anxiety	Psychiatric disorders	Systematic Assessment	EG0001 affected2 at risk EG0014 affected5 at risk EG0020 affected3 at risk EG003
Insomnia	Psychiatric disorders	Systematic Assessment	EG0001 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Depression	Psychiatric disorders	Systematic Assessment	EG0000 affected2 at risk EG0011 affected5 at risk EG0020 affected3 at risk EG003
Suicidal Ideation	Psychiatric disorders	Non-systematic Assessment	EG0000 affected2 at risk EG0011 affected5 at risk EG0020 affected3 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Hypersensitivity	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Tremor	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Posttraumatic stress disorder	Psychiatric disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Exposure to violent event	Social circumstances	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Anger	Psychiatric disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Major depression	Psychiatric disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Drowsiness	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Heavy legs	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Increased irritability	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Jaw Clenching, Tight Jaw	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Lack of Appetite	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Low mood	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Muscle tension	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Need more sleep	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Perspiration	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Restlessness	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Thirst	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003
Weakness	General disorders	Systematic Assessment	EG0000 affected2 at risk EG0010 affected5 at risk EG0020 affected3 at risk EG003

ID	Term
D013313	Stress Disorders, Post-Traumatic

ID	Term
D018817	N-Methyl-3,4-methylenedioxyamphetamine
D011613	Psychotherapy

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0074 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0072 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0075 affected5 at risk

EG0081 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0075 affected5 at risk

EG0081 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0051 affected5 at risk

EG0060 affected3 at risk

EG0070 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0071 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0075 affected5 at risk

EG0082 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0071 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0072 affected5 at risk

EG0081 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0072 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0071 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0073 affected5 at risk

EG0082 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0072 affected5 at risk

EG0082 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0073 affected5 at risk

EG0081 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0071 affected5 at risk

EG0080 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0073 affected5 at risk

EG0082 affected3 at risk

EG0040 affected2 at risk

EG0050 affected5 at risk

EG0060 affected3 at risk

EG0071 affected5 at risk

ID	Term
D040921	Stress Disorders, Traumatic
D000068099	Trauma and Stressor Related Disorders
D001523	Mental Disorders

ID	Term
D000662	Amphetamines
D010627	Phenethylamines
D005021	Ethylamines
D000588	Amines
D009930	Organic Chemicals
D004191	Behavioral Disciplines and Activities