Study Comparing Three Doses of MDMA Along With Psychotherapy in Veterans With Posttraumatic Stress Disorder
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ClinicalTrials.gov Identifier: NCT01211405 |
Recruitment Status :
Completed
First Posted : September 29, 2010
Last Update Posted : September 26, 2018
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Condition or disease | Intervention/treatment | Phase |
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Posttraumatic Stress Disorder | Drug: Low dose MDMA Drug: Medium dose MDMA Drug: Full dose MDMA Behavioral: Psychotherapy | Phase 2 |
Posttraumatic stress disorder (PTSD) is a debilitating mental disorder, that can develop after service in the armed forces. Psychotherapy performed along with MDMA is an innovative form of therapy for posttraumatic stress disorder. This study will follow on the findings of an initial pilot study in a sample largely made up of people whose PTSD did not develop from serving in the military. This study will investigate whether MDMA-assisted psychotherapy is safe and efficacious in a sample of veterans and whether maintaining an effective double-blind can be better addressed by performing a dose comparison study.
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 psychotherapy in veterans with chronic posttraumatic stress disorder. 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). An independent rater blind to condition will assess symptoms of PTSD and depression, general quality of life and posttraumatic growth prior to any psychotherapy sessions one month after the second experimental session.
After undergoing three 90-minute non-drug introductory psychotherapy sessions with a male/female co-therapist team, study participants will undergo two eight-hour long experimental sessions scheduled three to five weeks apart, during which they will randomly receive either 30, 75 or 125 mg MDMA on both occasions, followed by a supplemental dose of half the initial dose. Participants will undergo integrative psychotherapy 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 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 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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 26 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction With Manualized Psychotherapy in 24 Veterans, Firefighters and Police Officers With Chronic Posttraumatic Stress Disorder (PTSD) |
Study Start Date : | October 2010 |
Actual Primary Completion Date : | October 2016 |
Actual Study Completion Date : | November 2016 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Low dose MDMA
Participants will receive 30 mg MDMA during each of two blinded experimental sessions.
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Drug: 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
Other Names:
Behavioral: Psychotherapy Psychotherapy throughout main study |
Active Comparator: Medium dose MDMA
Participants will receive 75 mg MDMA on each of two blinded experimental sessions
|
Drug: 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
Other Names:
Behavioral: Psychotherapy Psychotherapy throughout main study |
Experimental: Full dose MDMA
Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session.
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Drug: 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.
Other Names:
Behavioral: Psychotherapy Psychotherapy throughout main study |
- Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Baseline ]Clinician-administered and scored assessment of posttraumatic stress disorder (PTSD) following diagnostic criteria found in DSM IV.It produces a global score, a dichotomous diagnostic scale, and subscales
- Clinician-Administered PTSD Scale (CAPS) [ Time Frame: One mo after Experimental Session 2 ]Clinician-administered and scored assessment of posttraumatic stress disorder (PTSD) following diagnostic criteria found in DSM IV.It produces a global score, a dichotomous diagnostic scale, and subscales
- Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Two months after Experimental Session 3 ]Clinician-administered and scored assessment of posttraumatic stress disorder (PTSD) following diagnostic criteria found in DSM IV.It produces a global score, a dichotomous diagnostic scale, and subscales
- Clinician-Administered PTSD Scale (CAPS) [ Time Frame: 12 month follow up ]Clinician-administered and scored assessment of posttraumatic stress disorder (PTSD) following diagnostic criteria found in DSM IV.It produces a global score, a dichotomous diagnostic scale, and subscales
- Global Assessment of Function (GAF) [ Time Frame: Baseline ]A single-item clinician-assessed measure of psychological function and well-being
- BDI-II [ Time Frame: Baseline ]Self-report measure of depression symptoms
- Posttraumatic Growth Inventory [ Time Frame: Baseline ]A self-report measure assessing potential benefits or reframing of traumatic event or events
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Every face to face visit, two of 7 phone contact days, 12 month follow up ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Body temperature [ Time Frame: Every 60-90 minutes throughout first 8-h experimental sessionm ]Body temperature assessed via tympanic thermometer
- Global Assessment of Function (GAF) [ Time Frame: One month after Experimetnal Session 2 ]A single-item clinician-assessed measure of psychological function and well-being
- Global Assessment of Function (GAF) [ Time Frame: Two months after Experimental Session 3 ]A single-item clinician-assessed measure of psychological function and well-being
- Global Assessment of Function (GAF) [ Time Frame: 12 month follow up ]A single-item clinician-assessed measure of psychological function and well-being
- BDI-II [ Time Frame: One month after Experimental Session 2 ]Self-report measure of depression symptoms
- BDI-II [ Time Frame: Two months after Experimental Session 3 ]Self-report measure of depression symptoms
- BDI-II [ Time Frame: 12 month follow up ]Self-report measure of depression symptoms
- Posttraumatic Growth Inventory [ Time Frame: One month after Experimental Session 2 ]A self-report measure assessing potential benefits or reframing of traumatic event or events
- Posttraumatic Growth Inventory [ Time Frame: Two months after Experimental Session 3 ]A self-report measure assessing potential benefits or reframing of traumatic event or events
- Posttraumatic Growth Inventory [ Time Frame: 12 month follow up ]A self-report measure assessing potential benefits or reframing of traumatic event or events
- Peak Body temperature [ Time Frame: Peak value from measurements made every 60-90 minutes throughout second 8-h experimental sessionm ]Body temperature assessed via tympanic thermometer
- Peak Body temperature [ Time Frame: Peak value from measurements made every 60-90 minutes throughout third 8-h experimental sessionm ]Body temperature assessed via tympanic thermometer
- Peak blood pressure (systolic) [ Time Frame: Peak value from measuremades made every 15-30 min throughout first eight-hour experimental session ]Measuring systolic blood pressure
- Peak blood pressure (systolic) [ Time Frame: Peak value from measurements made every 15-30 min throughout second eight-hour experimental session ]Measuring systolic blood pressure
- Peak blood pressure (systolic) [ Time Frame: Peak value from measurements made every 15-30 min throughout third eight-hour experimental session ]Measuring systolic blood pressure
- Peak Pulse [ Time Frame: Peak value from measurements made every 15-30 min throughout first eight-hour experimental session ]Assessing heart rate via pulse
- Peak Pulse [ Time Frame: Peak value from measurement made every 15-30 min throughout second eight-hour experimental session ]Assessing heart rate via pulse
- Peak Pulse [ Time Frame: Peak value from measurements made every 15-30 min throughout third eight-hour experimental session ]Assessing heart rate via pulse
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Session prior to first experimental session ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Twice during first experimental session ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Twice during second experimental session ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Twice during third experimental session ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 12 month follow up ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: First psychotherapy session after experimental session 1 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Second psychotherapy session after experimental session 1 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Third psychotherapy session after experimental session 1 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: First psychotherapy session after experimental session 2 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Second psychotherapy session after experimental session 2 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Third psychotherapy session after experimental session 2 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: First psychotherapy session after experimental session 3 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Second psychotherapy session after experimental session 3 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Third psychotherapy session after experimental session 3 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Phone contact days 2 and 7 after experimental session 1 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Phone contact days 2 and 7 after experimental session 2 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Phone contact days 2 and 7 after experimental session 3 ]A clinician-administered and scored measure of suicidal ideation and behavior, consisting of series of questions and adaptive to responses to questions.
- Peak Subjective Units of Distress [ Time Frame: Peak value from measurements made every sixty-ninety minutes during experimental session 1 ]Single item assesses self-reported psychological distress
- Peak Subjective Units of Distress [ Time Frame: Peak value from measurements made every sixty-ninety minutes during experimental session 2 ]Single item assesses self-reported psychological distress
- Peak Subjective Units of Distress [ Time Frame: Peak value from measurements made every sixty-ninety minutes during experimental session 3 ]Single item assesses self-reported psychological distress
- Pittsburgh Sleep Quality Index [ Time Frame: Baseline ]Self-report measure of sleep quality
- Pittsburgh Sleep Quality Index [ Time Frame: One month after Experimental Session 2 ]Self-report measure of sleep quality
- Pittsburgh Sleep Quality Index [ Time Frame: Two months after Experimental Session 3 ]Self-report measure of sleep quality
- States of Consciousness Questionnaire [ Time Frame: After experimental session 1 ]Assesses subjective effects and experience of alterations in consciousness
- States of Consciousness Questionnaire [ Time Frame: After experimental session 2 ]Assesses subjective effects and experience of alterations in consciousness
- States of Consciousness Questionnaire [ Time Frame: After experimental session 3 ]Assesses subjective effects and experience of alterations in consciousness
- Neuroticism Extroversion Openness Inventory (NEO) [ Time Frame: Baseline ]Self-report, Assesses five personality factors
- Neuroticism Extroversion Openness Inventory (NEO) [ Time Frame: 1 months after Experimental Session 2 ]Self-report, Assesses five personality factors
- Neuroticism Extroversion Openness Inventory (NEO) [ Time Frame: 12 months after Experimental Session 3 ]Self-report, Assesses five personality factors
- Pre-drug body temperature [ Time Frame: Body temperature prior to drug administration during first experimental session ]Body temperature assessed via tympanic thermometer
- Peak body temperature [ Time Frame: Peak value from measurements made every 60-90 nin during first experimental session ]Body temperature assessed via tympanic thermometer
- Pre-drug body temperature [ Time Frame: Body temperature prior to drug administration during second experimental session ]Body temperature assessed via tympanic thermometer
- Pre-drug body temperature [ Time Frame: Body temperature prior to drug administration during third experimental session ]Body temperature assessed via tympanic thermometer
- Endpoint body temperature [ Time Frame: Body temperature 7 h +/-30 min post drug administration during first experimental session ]Body temperature assessed via tympanic thermometer
- Endpoint body temperature [ Time Frame: Body temperature 7 h +/- 30 min post drug administration during second experimental session ]Body temperature assessed via tympanic thermometer
- Endpoint body temperature [ Time Frame: Body temperature 7 h +/- 30 min post drug administration during third experimental session ]Body temperature assessed via tympanic thermometer
- Pre-drug Pulse [ Time Frame: Pre-drug value at first eight-hour experimental session ]Assessing heart rate via pulse
- Endpoint Pulse [ Time Frame: Pulse 7 h +/- 30 min post drug on first 8-hour experimental session ]Assessing heart rate via pulse
- Pre-drug Pulse [ Time Frame: Pre-drug pulse on second eight-hour experimental session ]Assessing heart rate via pulse
- Endpoint Pulse [ Time Frame: Pulse 7 h +/- 30 min post-drug on second eight-hour experimental session ]Assessing heart rate via pulse
- Pre-drug Pulse [ Time Frame: Pre-drug pulse on the third eight-hour experimental session ]Assessing heart rate via pulse
- Endpoint Pulse [ Time Frame: Pulse 7 h +/- 30 min post-drug on third eight-hour experimental session ]Assessing heart rate via pulse
- Peak blood pressure (diastolic) [ Time Frame: Peak value from measuremades made every 15-30 min throughout first eight-hour experimental session ]Measuring diastolic blood pressure
- Peak lood pressure (diastolic) [ Time Frame: Peak value from measurements made every 15-30 min throughout second eight-hour experimental session ]Measuring diastolic blood pressure
- Peak blood pressure (diastolic) [ Time Frame: Peak value from measurements made every 15-30 min throughout third eight-hour experimental session ]Measuring diastolic blood pressure
- Pre-drug blood pressure [ Time Frame: Prior to drug administration on first experimental session ]Measurement of blood pressure as systolic/diastolic
- Endpoint blood pressure [ Time Frame: Value at 7 h +/- 30 min post-drug on first 8-hour experimental session ]Measurement of blood pressure as systolic/diastolic
- Pre-drug blood pressure [ Time Frame: Value prior to drug administration on second experimental session ]Measurement as systolic/diastolic
- Endpoint blood pressure [ Time Frame: Value 7 h +/- 30 min post-drug on second 8-hour ecxperimental session ]Measurement of blood pressure as systolic/diastolic
- Pre-drug blood pressure [ Time Frame: Value prior to drug administration on third experimental session ]Measurement of blood pressure as systolic/diastolic
- Endpoint blood pressure [ Time Frame: Value 7 h +/- 30 min post-drug on third 8-hour experimental session ]Measurement of blood pressure as systolic/diastolic

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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:
5.3.2 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;
- 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 s

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01211405
United States, South Carolina | |
Offices of Michael Mithoefer | |
Mount Pleasant, South Carolina, United States, 29464-4345 |
Principal Investigator: | Michael C Mithoefer, MD | Private Practice |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Multidisciplinary Association for Psychedelic Studies |
ClinicalTrials.gov Identifier: | NCT01211405 |
Other Study ID Numbers: |
MP-8 |
First Posted: | September 29, 2010 Key Record Dates |
Last Update Posted: | September 26, 2018 |
Last Verified: | September 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | We will share outcome data appearing in any published reports upon request. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) |
Time Frame: | Data and study-related documents will be available when all participants have completed the study |
Access Criteria: | Interested persons should correspond with the central contact for the study. |
MDMA Psychotherapy Veterans Posttraumatic Stress Disorder |
Disease Stress Disorders, Traumatic Stress Disorders, Post-Traumatic Pathologic Processes Trauma and Stressor Related Disorders Mental Disorders N-Methyl-3,4-methylenedioxyamphetamine Hallucinogens Physiological Effects of Drugs |
Psychotropic Drugs Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Adrenergic Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Adrenergic Agents |