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

Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction With Manualized Therapy in 24 Veterans, Firefighters and Police Officers With Chronic Posttraumatic Stress Disorder (PTSD)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01211405

Enrollment

Registered

2010-09-29

Start date

2010-11-10

Completion date

2016-08-02

Last updated

2025-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Posttraumatic Stress Disorder

Keywords

MDMA, Therapy, Veterans, Posttraumatic Stress Disorder

Brief summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective and reducing PTSD symptoms in veterans with chronic PTSD. The main question it aims to answer is: Do three doses of MDMA reduce PTSD symptoms? Researchers will compare 30, 75, and 125 mg of MDMA HCl with therapy to see which dose best reduces PTSD symptoms. Participants will undergo three preparatory non-drug therapy sessions with a male and female co-therapist team, then undergo three day-long MDMA-assisted therapy sessions after receiving an initial dose of 30, 75, or 125 mg MDMA HCl. After each MDMA-assisted therapy session, participants will undergo three integrative therapy sessions.

Detailed description

This study is a randomized, double-blind, dose comparison study with an open-label cross-over segment that will assess the safety and efficacy of MDMA-assisted therapy in veterans with chronic PTSD. Twelve of 24 participants will receive the full dose of 125 mg, six will receive 75 mg and six will receive 30 mg (active placebo dose) of MDMA HCl. An independent rater blind to condition will assess symptoms of PTSD and depression, general quality of life and posttraumatic growth prior to any therapy sessions one month after the second experimental session. After undergoing three 90-minute non-drug introductory therapy sessions with a male/female co-therapist team, study participants will undergo two eight-hour long experimental sessions scheduled three to five weeks apart, prior to which they will be randomized to receive an initial dose of 30, 75 or 125 mg MDMA HCl , followed by a supplemental dose of half the initial dose 1.5 to 2.5 hours later. Participants will undergo integrative therapy in between each experimental session, including on the day after each session. Vital signs and psychological distress will be measured throughout each experimental session, and suicidality will be assessed throughout the course of the study. Spontaneously reported side effects will be collected on the day of each experimental session, and for six days afterward. PTSD symptoms, symptoms of depression, general psychological function, posttraumatic growth and quality of sleep will be assessed one month after the second experimental session, and the blind will be broken. Participants who received 125 mg MDMA HCl will continue to have a third experimental session, and they will be assessed two months after the third experimental session. Participants who received 30 or 75 mg MDMA HCl may take part in an open-label crossover segment that will follow nearly identical procedures, except that there will only be one introductory session prior to the first experimental session. There will be three experimental sessions. Symptoms of PTSD, depression and posttraumatic growth will be assessed at the start of the study. They will also be assessed one month after the second and two months after the third experimental session. All participants will be assessed 12 months after their final experimental session. PTSD and depression symptoms and posttraumatic growth will be assessed, and participants will complete a questionnaire concerning the costs and benefits of being in the study.

Interventions

DRUGLow dose MDMA-assisted therapy

30 mg midomafetamine HCl administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 15 mg 1.5 to 2 hours later

DRUGMedium dose MDMA-assisted therapy

75 mg midomafetamine HCl administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 37.5 mg 1.5 to 2 hours later

DRUGFull dose MDMA-assisted therapy

125 mg midomafetamine HCl administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 62.5 mg 1.5 to 2 hours later

BEHAVIORALTherapy

Non-directive therapy during each session

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Be diagnosed with chronic PTSD, duration of 6 months or longer resulting from traumatic experience during military service; * Have a CAPS score showing moderate to severe PTSD symptoms; * Have had at least one unsuccessful attempt at treatment for PTSD either with talk therapy or with drugs, or discontinuing treatment because of inability to tolerate psychotherapy or drug therapy. * Are at least 18 years old; * Must be 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; * Willing to follow restrictions and guidelines concerning consumption of food, beverages, and nicotine the night before and just prior to each experimental session; * Willing to remain overnight at the study site; * Agree to have transportation other than driving themselves home or to where they are staying after the integrative session on the day after the MDMA session; * 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; * Must provide a contact in the event of a participant becoming suicidal; * Are proficient in speaking and reading English; * Agree to have all clinic visit sessions recorded to audio and video * Agree not to participate in any other interventional clinical trials during the duration of this study.

Exclusion criteria

* Are pregnant or nursing, or if a woman who can have children, those who are not practicing an effective means of birth control; * Weigh less than 48 kg; * Are abusing illegal drugs; * Have used ecstasy (material representing itself as MDMA) more than 5 times or at least once in the last 6 months; * 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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Change in Global Assessment of Function (GAF) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Posttraumatic Growth Inventory (PTGI) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Beck Depression Inventory (BDI-II) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Dissociative Experience Scale (DES-II) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Low Dose MDMA (30 mg) 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	7
Medium Dose MDMA (75 mg) 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	7
Full Dose MDMA (125 mg) 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	12
Total	26

Baseline characteristics

Characteristic	Low Dose MDMA (30 mg)	Medium Dose MDMA (75 mg)	Full Dose MDMA (125 mg)	Total
Age, Continuous	39.2 years STANDARD_DEVIATION 9.7	29.1 years STANDARD_DEVIATION 4	40.7 years STANDARD_DEVIATION 11.1	37.2 years STANDARD_DEVIATION 10.3
Race/Ethnicity, Customized Ethnicity Latino/Hispanic	1 Participants	1 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Ethnicity Native American	0 Participants	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Ethnicity Other	0 Participants	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Ethnicity White/Caucasian	6 Participants	4 Participants	12 Participants	22 Participants
Sex: Female, Male Female	2 Participants	1 Participants	4 Participants	7 Participants
Sex: Female, Male Male	5 Participants	6 Participants	8 Participants	19 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 7	0 / 12	0 / 6	0 / 6	0 / 12	0 / 6	0 / 7	0 / 11	0 / 7	0 / 7	0 / 12
other Total, other adverse events	6 / 7	4 / 7	8 / 12	6 / 6	4 / 6	4 / 12	0 / 6	0 / 7	0 / 11	7 / 7	7 / 7	12 / 12
serious Total, serious adverse events	1 / 7	0 / 7	0 / 12	1 / 6	0 / 6	0 / 12	1 / 6	1 / 7	0 / 11	0 / 7	0 / 7	0 / 12

Outcome results

Primary

Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to Primary Endpoint

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.