Study Comparing Three Doses of MDMA Along With Therapy in Veterans With Posttraumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT01211405
• Recruitment Status: Completed
• First Posted: September 29, 2010
• Results First Posted: February 2, 2022
• Last Update Posted: July 11, 2022
• Sponsor: Multidisciplinary Association for Psychedelic Studies
• Information provided by (Responsible Party): Multidisciplinary Association for Psychedelic Studies

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Posttraumatic Stress Disorder
• Interventions: Drug: Low dose MDMA; Drug: Medium dose MDMA; Drug: Full dose MDMA; Behavioral: Therapy
• Enrollment: 26

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Period Title: Overall Study
Started	7	7	12
Completed Primary Endpoint	7	7	12
Completed Three Open-Label Sessions, Secondary, and End of Stage 2 Assessment	6	6	12
Completed [1]	6	7	11
Not Completed	1	0	1
[1] Completed 12-month follow-up

Baseline Characteristics

Arm/Group Title		Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)	Total
Arm/Group Description		Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session	Total of all reporting groups
Overall Number of Baseline Participants		7	7	12	26
Baseline Analysis Population Description		Intent-to-treat
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	7 participants	7 participants	12 participants	26 participants
		39.2 (9.7)	29.1 (4.0)	40.7 (11.1)	37.2 (10.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	12 participants	26 participants
	Female	2 28.6%	1 14.3%	4 33.3%	7 26.9%
	Male	5 71.4%	6 85.7%	8 66.7%	19 73.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Ethnicity	Number Analyzed	7 participants	7 participants	12 participants	26 participants
	White	6 85.7%	4 57.1%	12 100.0%	22 84.6%
	Latino or Hispanic	1 14.3%	1 14.3%	0 0.0%	2 7.7%
	Native American	0 0.0%	1 14.3%	0 0.0%	1 3.8%
	Native American and White	0 0.0%	1 14.3%	0 0.0%	1 3.8%
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	7 participants	7 participants	12 participants	26 participants
		32.5 (4.7)	27.9 (5.4)	27.5 (3.6)	29.0 (4.8)
Occupation associated with trauma; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	12 participants	26 participants
	Military	6 85.7%	7 100.0%	9 75.0%	22 84.6%
	Firefighter	1 14.3%	0 0.0%	2 16.7%	3 11.5%
	Police officer	0 0.0%	0 0.0%	1 8.3%	1 3.8%
Duration of PTSD; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	7 participants	7 participants	12 participants	26 participants
		68.9 (15.0)	58.3 (32.3)	110.9 (85.1)	85.4 (63.9)

Outcome Measures

1. Primary Outcome

Title	Baseline Clinician-Administered PTSD Scale (CAPS-IV) Total Score
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	87.4 (14.1)	82.4 (17.3)	89.7 (17.3)

2. Primary Outcome

Title	Primary Endpoint Clinician-Administered PTSD Scale (CAPS-IV) Total Score
Description	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	One month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	76.0 (23.4)	24.1 (17.2)	45.3 (33.8)

3. Primary Outcome

Title	Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to Primary Endpoint
Description	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 one month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-11.4 (12.7)	-58.3 (9.8)	-44.3 (28.7)

4. Secondary Outcome

Title	Change in Global Assessment of Function (GAF) From Baseline to Primary Endpoint
Description	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 one month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	1.1 (4.6)	19.4 (6.1)	18.4 (14.4)

5. Secondary Outcome

Title	Change in Posttraumatic Growth Inventory (PTGI) From Baseline to Primary Endpoint
Description	The Posttraumatic Growth Inventory (PTGI) is a 21-item self-report measure of perceived growth or benefits occurring after a traumatic event. It contains five subscales; relationship to others, new possibilities, personal strength, spiritual change, and appreciation of life. Questions are answered on a scale from 0 (I did not experience this change) to 5 (I experienced this change to a great degree). Items are added to calculate the total PTGI score which ranges from 0 to 105, with higher scores indicative of greater growth.
Time Frame	Baseline to one month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-11.6 (12.2)	36.1 (12.0)	33.7 (24.0)

6. Secondary Outcome

Title	Change in Beck Depression Inventory (BDI-II) From Baseline to Primary Endpoint
Description	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 one month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-4.6 (8.8)	-15.4 (9.5)	-24.6 (10.6)

7. Secondary Outcome

Title	Change in Dissociative Experience Scale (DES-II) From Baseline to Primary Endpoint
Description	The DES-II is a 28-item self-report measure of dissociation, defined as a lack of normal integration of an individual's thoughts, feelings, or experiences into the stream of consciousness or memory. Respondents indicate how often the specific experience happens to them, from "never" (0% of the time) to "always" (100%). The scale is scored by treating percentages as single digits and summing to produce a total score, ranging from 0 to 100. The higher the score, the more dissociative symptoms.
Time Frame	Baseline to one month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	1.8 (0.9)	-8.6 (1.9)	-8.8 (6.2)

8. Secondary Outcome

Title	Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Primary Endpoint
Description	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 one month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	1.8 (2.8)	-6.4 (7.1)	-4.8 (4.1)

9. Secondary Outcome

Title	Change in Neuroticism-Extroversion-Openness Personality Inventory-Revised (NEO-PI-R) From Baseline to Primary Endpoint
Description	The NEO-PI-R is a 240-item self-report assessment that defines personality structure according to a five-factor model. Items related to neuroticism, extraversion, openness, agreeableness, and conscientiousness are rated on a five-point scale from strongly disagree to strongly agree. T-scores range from 20 to 80 with a mean score of 50. Higher scores in each domain indicating stronger facets of those personality factors. The NEO-PI-R is a measure of personality traits, not psychopathology symptoms.
Time Frame	Baseline to one month after second experimental session

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)
Arm/Group Description:	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
Overall Number of Participants Analyzed	7	7	12
Mean (Standard Deviation); Unit of Measure: T-score
Baseline Neuroticism	62.0 (14.8)	65.3 (11.4)	75.1 (6.4)
One month after 2nd Experimental Session Neuroticism	60.2 (14.9)	53.6 (12.4)	58.6 (12.8)
Change in Neuroticism	-4.6 (5.5)	-12.0 (3.6)	-16.5 (11.8)
Baseline Extroversion	33.1 (9.4)	37.4 (8.9)	34.2 (8.5)
One month after 2nd Experimental Session Extroversion	36.0 (11.2)	46.4 (8.6)	42.2 (13.3)
Change in Extroversion	2.2 (4.3)	10.0 (9.4)	8.0 (9.4)
Baseline Openness	48.9 (9.6)	55.6 (12.1)	57.4 (16.7)
One Month after 2nd Experimental Session Openness	49.2 (10.2)	66.0 (7.8)	59.4 (9.9)
Change in Openness	-0.6 (9.9)	15.6 (5.3)	2.0 (10.5)
Baseline Agreeableness	44.7 (8.0)	33.1 (15.2)	39.8 (13.7)
One Month after 2nd Experimental Session	40.6 (13.6)	33.4 (9.6)	45.7 (11.4)
Change in Agreeableness	-1.2 (8.4)	5.4 (8.0)	5.9 (4.9)
Baseline Conscientiousness	41.3 (9.9)	53.6 (18.3)	41.3 (13.5)
One Month after 2nd Experimental Session Conscientiousness	39.8 (6.8)	56.4 (10.1)	47.8 (10.0)
Change in Conscientiousness	-3.2 (7.9)	2.4 (15.0)	6.5 (13.4)

Adverse Events

Time Frame	Over the entire course of the study (approx 12 months)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Low Dose MDMA (30 mg)		Medium Dose MDMA (75 mg)		Full Dose MDMA (125 mg)
Arm/Group Description	Participants will receive 30 mg MDMA during each of two blinded experimental sessions. Low dose MDMA: 30 mg MDMA administered p.o. once during each experimental session. Upon mutual agreement this maybe followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later Psychotherapy: Non-directive psychotherapy during each session		Participants will receive 75 mg MDMA on each of two blinded experimental sessions Medium dose MDMA: 75 mg MDMA adminis5tered p.o. once at start of an experimental session. Upon mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 37.5 mg Psychotherapy: Non-directive psychotherapy during each session		Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. Full dose MDMA: 125 mg MDMA administered p.o. at start of an experimental session. By mutual agreement, may be followed 1.5 to 2 hours later by a supplemental dose of 62.5 mg MDMA. Psychotherapy: Non-directive psychotherapy during each session
All-Cause Mortality
	Low Dose MDMA (30 mg)		Medium Dose MDMA (75 mg)		Full Dose MDMA (125 mg)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/7 (0.00%)		0/7 (0.00%)		0/12 (0.00%)
Serious Adverse Events
	Low Dose MDMA (30 mg)		Medium Dose MDMA (75 mg)		Full Dose MDMA (125 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.29%)		1/7 (14.29%)		0/12 (0.00%)
Cardiac disorders
Ventricular extrasystoles *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Infections and infestations
Appendicitis *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Psychiatric disorders
Suicidal Ideation *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Depression *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Low Dose MDMA (30 mg)		Medium Dose MDMA (75 mg)		Full Dose MDMA (125 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/7 (85.71%)		3/7 (42.86%)		8/12 (66.67%)
Ear and labyrinth disorders
Tinnitus *	1/7 (14.29%)		0/7 (0.00%)		1/12 (8.33%)
Tinnitus *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Endocrine disorders
Hypothyroidism *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Eye disorders
Visual impairment *	0/7 (0.00%)		2/7 (28.57%)		0/12 (0.00%)
Dry eye *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Vitreous floaters *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Gastrointestinal disorders
Diarrhea *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Abdominal pain *	1/7 (14.29%)	2	0/7 (0.00%)		1/12 (8.33%)
Constipation *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Irritable bowel syndrome *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Vomiting *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
General disorders
Fatigue *	2/7 (28.57%)		0/7 (0.00%)		0/12 (0.00%)
Cyst *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Infections and infestations
Hordeolum *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Influenza *	1/7 (14.29%)		1/7 (14.29%)		0/12 (0.00%)
Sinusitis *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Tooth abscess *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Pneumonia *	0/7 (0.00%)		1/7 (14.29%)		1/12 (8.33%)
Urinary Tract Infection *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Vaginal Infection *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Sinusitis *	1/7 (14.29%)		1/7 (14.29%)		0/12 (0.00%)
Tinea pedis *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Injury, poisoning and procedural complications
Ligament Sprain *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Venomous sting *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Contusion *	0/7 (0.00%)		0/7 (0.00%)		2/12 (16.67%)
Skin Abrasion *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Tooth injury *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Joint dislocation *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Metabolism and nutrition disorders
Vitamin D deficiency *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Decreased appetite *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain *	1/7 (14.29%)		0/7 (0.00%)		1/12 (8.33%)
Arthralgia *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Myalgia *	2/7 (28.57%)		0/7 (0.00%)		0/12 (0.00%)
Joint stiffness *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Musculoskeletal stiffness *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Nervous system disorders
Hypersomnia *	3/7 (42.86%)	4	0/7 (0.00%)		0/12 (0.00%)
Migraine *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Headache *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Dizziness *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Psychiatric disorders
Anxiety *	3/7 (42.86%)	4	0/7 (0.00%)		1/12 (8.33%)	2
Depressed Mood *	2/7 (28.57%)		0/7 (0.00%)		0/12 (0.00%)
Negative thoughts *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Time perception altered *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Trichotillomania *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Flashback *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Insomnia *	0/7 (0.00%)		0/7 (0.00%)		2/12 (16.67%)
Irritability *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Tic *	0/7 (0.00%)		0/7 (0.00%)		1/12 (8.33%)
Hypnagogic hallucination *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Hypnopompic hallucination *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Nasal congestion *	2/7 (28.57%)	3	0/7 (0.00%)		0/12 (0.00%)
Oropharyngeal pain *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Skin and subcutaneous tissue disorders
Urticaria *	1/7 (14.29%)		0/7 (0.00%)		0/12 (0.00%)
Petechiae *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Pseudofolliculitis barbae *	0/7 (0.00%)		1/7 (14.29%)		0/12 (0.00%)
Pruritus *	2/7 (28.57%)		0/7 (0.00%)		0/12 (0.00%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Julie B. Wang, MPH, PhD/ Senior Clinical Data Scientist
• Organization: Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corp.
• Phone: (831) 429-6362
• EMail: juliewang@mapsbcorp.com

Publications of Results:

Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, Holland J, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018 Jun;5(6):486-497. doi: 10.1016/S2215-0366(18)30135-4. Epub 2018 May 1.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Multidisciplinary Association for Psychedelic Studies
• ClinicalTrials.gov Identifier: NCT01211405
• Other Study ID Numbers: MP-8
• First Submitted: August 6, 2010
• First Posted: September 29, 2010
• Results First Submitted: August 25, 2021
• Results First Posted: February 2, 2022
• Last Update Posted: July 11, 2022