Trial Outcomes & Findings for A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2) (NCT NCT04077437)

Last Updated: 2025-06-06

Results Overview

The CAPS-5 is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

121 participants

Primary outcome timeframe

Baseline to 18 weeks post baseline post enrollment confirmation

Results posted on

2025-06-06

Participant Flow

Participants were recruited through print and internet advertisements, referrals from other treatment providers, and by word of mouth.

Participant milestones

Participant milestones
Measure	Experimental: MDMA-assisted Psychotherapy Administration of 80 to 120 mg midomafetamine HCl in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg offered 1.5 to 2 hrs after the initial dose, respectively.	Placebo Comparator: Placebo With Psychotherapy Administration of inactive placebo in combination with psychotherapy.
Overall Study STARTED	53	51
Overall Study COMPLETED	52	42
Overall Study NOT COMPLETED	1	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: MDMA-assisted Psychotherapy n=53 Participants Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Placebo Comparator: Placebo With Psychotherapy n=51 Participants Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.	Total n=104 Participants Total of all reporting groups
Age, Continuous	38.2 years STANDARD_DEVIATION 11.0 • n=5 Participants	39.9 years STANDARD_DEVIATION 9.6 • n=7 Participants	39.1 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	42 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	9 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants	39 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants	32 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Baseline PTSD Duration	16.3 years STANDARD_DEVIATION 14.3 • n=5 Participants	16.1 years STANDARD_DEVIATION 12.4 • n=7 Participants	16.2 years STANDARD_DEVIATION 13.3 • n=5 Participants
Baseline CAPS-5 Dissociative Subtype	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 18 weeks post baseline post enrollment confirmation

Outcome measures

Outcome measures
Measure	Experimental: MDMA-assisted Psychotherapy n=53 Participants Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Placebo Comparator: Placebo With Psychotherapy n=50 Participants Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.
Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5)	-23.69 score on a scale Interval -26.94 to -20.44	-14.78 score on a scale Interval -18.28 to -11.28

SECONDARY outcome

Timeframe: Baseline to 18 weeks post enrollment confirmation

The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.

Outcome measures

Outcome measures
Measure	Experimental: MDMA-assisted Psychotherapy n=53 Participants Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Placebo Comparator: Placebo With Psychotherapy n=50 Participants Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.
Change From Baseline to Primary Endpoint in Adapted Sheehan Disability Scale (SDS) Total Score	-3.31 score on a scale Interval -4.03 to -2.6	-2.11 score on a scale Interval -2.89 to -1.33

Adverse Events

MDMA-assisted Therapy

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

Placebo With Therapy

Serious events: 0 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Study Director

Lykos Therapeutics

Phone: 877-627-7722

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	MDMA-assisted Therapy n=53 participants at risk Administration of 80 to 120 mg midomafetamine HCl in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg offered 1.5 to 2 hrs after the initial dose, respectively.	Placebo With Therapy n=51 participants at risk Administration of inactive placebo in combination with psychotherapy.
Cardiac disorders Palpitations	9.4% 5/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Eye disorders Vision blurred	15.1% 8/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Eye disorders Mydriasis	11.3% 6/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Eye disorders Visual impairment	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Gastrointestinal disorders Nausea	45.3% 24/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	21.6% 11/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Gastrointestinal disorders Dry mouth	17.0% 9/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	7.8% 4/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Gastrointestinal disorders Abdominal discomfort	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Gastrointestinal disorders Abdominal pain upper	9.4% 5/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Gastrointestinal disorders Vomiting	7.5% 4/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	3.9% 2/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Gastrointestinal disorders Abdominal pain	3.8% 2/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Gastrointestinal disorders Diarrhoea	1.9% 1/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Fatigue	26.4% 14/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	17.6% 9/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Feeling hot	26.4% 14/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	11.8% 6/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Feeling cold	20.8% 11/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Chest discomfort	17.0% 9/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	3.9% 2/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Chills	15.1% 8/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Feeling jittery	15.1% 8/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Feeling abnormal	9.4% 5/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	3.9% 2/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Feeling of body temperature change	9.4% 5/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Thirst	7.5% 4/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
General disorders Gait disturbance	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Infections and infestations COVID-19	7.5% 4/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	7.8% 4/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Infections and infestations Upper respiratory tract infection	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Investigations Heart rate increased	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Metabolism and nutrition disorders Decreased appetite	35.8% 19/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	9.8% 5/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Musculoskeletal and connective tissue disorders Muscle tightness	58.5% 31/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	25.5% 13/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Musculoskeletal and connective tissue disorders Myalgia	13.2% 7/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	7.8% 4/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Musculoskeletal and connective tissue disorders Neck pain	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	13.7% 7/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Musculoskeletal and connective tissue disorders Pain in jaw	11.3% 6/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	7.8% 4/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 4/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	9.8% 5/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Musculoskeletal and connective tissue disorders Back pain	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Musculoskeletal and connective tissue disorders Muscle spasms	7.5% 4/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Nervous system disorders Headache	71.7% 38/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	60.8% 31/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Nervous system disorders Dizziness	28.3% 15/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	15.7% 8/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Nervous system disorders Paraesthesia	18.9% 10/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Nervous system disorders Nystagmus	13.2% 7/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Nervous system disorders Disturbance in attention	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Nervous system disorders Hypoaesthesia	9.4% 5/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Nervous system disorders Tremor	11.3% 6/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Suicidal ideation	34.0% 18/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	41.2% 21/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Insomnia	35.8% 19/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	29.4% 15/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Anxiety	28.3% 15/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	23.5% 12/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Depressed mood	9.4% 5/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	11.8% 6/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Restlesness	15.1% 8/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	3.9% 2/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Bruxism	13.2% 7/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Nightmare	7.5% 4/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Emotional disorder	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	3.9% 2/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Irritability	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	3.9% 2/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Panic attack	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Binge eating	0.00% 0/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Psychiatric disorders Dissociation	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	0.00% 0/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Skin and subcutaneous tissue disorders Hyperhidrosis	34.0% 18/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	5.9% 3/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Vascular disorders Flushing	5.7% 3/53 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)	2.0% 1/51 • During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)