A Test of MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT00090064
• Recruitment Status: Completed
• First Posted: August 25, 2004
• Last Update Posted: June 8, 2021
• Sponsor: Multidisciplinary Association for Psychedelic Studies
• Information provided by (Responsible Party): Multidisciplinary Association for Psychedelic Studies

Tracking Information

• First Submitted Date: August 24, 2004
• First Posted Date: August 25, 2004
• Last Update Posted Date: June 8, 2021
• Study Start Date: March 2004
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 25, 2008): Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Screening, baseline, four days after experimental session 1, four days after experimental session 2, 2 months after experimental session 2 ]
• Original Primary Outcome Measures (submitted: June 23, 2005): Improvement in PTSD symptoms, measured by CAPS score

Current Secondary Outcome Measures (submitted: July 25, 2008)

• PTSD symptoms, measured via Impact of Events Scale (IES) [ Time Frame: Baseline, four days after experimental session 1, four days after experimental session 2, two months after experimental session 2 ]
• PTSD symptoms through Symptom Checklist 90-R. (SCL-90-R) [ Time Frame: Baseline, four days after experimental session 1, four days after experimental session 2, two months after experimental session 2 ]
• Problem solving, Paced Auditory Serial Addition Task (PASAT) [ Time Frame: Baseline, two months after experimental session 2 ]
• Rey-Osterrieth Complex Figure Test [ Time Frame: Baseline, two months after experimental session 2 ]
• Psychological distress, Subjective Units of Distress (SUDS) [ Time Frame: every sixty to ninety minutes throughout each experimental or open-label session ]
• Cognitive function, Repeatable Battery for Assessment of Neuropsychological Status [ Time Frame: Baseline, two months after experimental session 2 ]

Original Secondary Outcome Measures (submitted: June 23, 2005)

• Improvement in PTSD symptoms as assessed through other measures
• No impairment in tests of attention, memory or problem-solving

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Test of MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder
• Official Title: Phase II Clinical Trial Testing the Safety and Efficacy of 3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy in Subjects With Chronic Posttraumatic Stress Disorder
• Brief Summary: This study is being conducted to find out if methylenedioxymethamphetamine (MDMA)-assisted psychotherapy is safe and can help people with posttraumatic stress disorder (PTSD) arising from being a victim of a crime.

Detailed Description

Posttraumatic stress disorder (PTSD) occurs in response to a traumatic event or events. It is most likely to occur following an event involving perceived personal threat, such as rape or physical assault. PTSD is clearly a public health problem that causes a great deal of suffering and accounts for a significant portion of health care costs. This study will examine whether two sessions of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy can be safely administered to participants with PTSD, and whether MDMA-assisted psychotherapy, when compared with placebo-assisted therapy, will reduce PTSD symptoms after each session and two months after the second session.

MDMA is a substance possessing unique effects that make it well suited to intensive psychotherapy. MDMA has been hypothesized to represent a new class of drugs, called entactogens, that produce feelings of closeness to others, empathy, well being, and insightfulness. Currently, MDMA is scheduled (illegal) and cannot be used outside of research studies like this one. Anecdotal reports of therapy conducted before MDMA was made illegal suggest that MDMA-assisted psychotherapy may benefit people with PTSD.

This study will examine MDMA-assisted psychotherapy in twenty people ages 18 to 70 with PTSD either related to crime victimization or combat, when combat-related PTSD lasts no longer than five years, and that has not gotten better after psychotherapy and treatment with an SSRI (selective serotonin uptake inhibitor, such as Paxil).

This study lasts three to four months. Participants attend up to fourteen (14) ordinary (non-drug) psychotherapy sessions with the investigators as well as two eight hour long experimental (MDMA or placebo) sessions and one MDMA session. People taking part in this study cannot take any psychiatric medication during the study period. People will either get 125 mg MDMA or placebo "by chance," as by coin-toss, with twelve of twenty (60%) getting MDMA during each experimental session, and eight of twenty (40%) getting placebo. Two to two and a half hours later, if you and the investigators agree it is alright, you will take a second supplemental, dose of MDMA or placebo. The supplemental dose will be half the size of the first dose. The same investigators conducting non-drug therapy sessions conduct the experimental sessions. All participants are required to stay the night at the clinic after each experimental session. Participants meet with the investigators for a non-drug assisted therapy session the day after each experimental session. A third MDMA session in this placebo-controlled stage of the study will only be for people who received MDMA in the first two sessions.

PTSD symptoms are measured at the start of the study, four days after each experimental session, and finally two months after the second experimental session. People are tested on memory and problem solving when they first enter the study and again two months after the second experimental session. PTSD symptoms are measured to see whether there are any changes in symptoms during the study, and tests of thinking, memory and problem-solving are meant to spot any changes that could be due to MDMA or MDMA-assisted therapy.

Participants who recieved MDMA who complete the final evaluation, and upon discussion with the investigators, will undergo a third MDMA session. The third session will happen approximately two months after the second experimental session This session is "open label," meaning that they and the investigators will both know they are receiving MDMA. It will be followed by one psychotherapy session a day after this session and two additional psychotherapy sessions in the following weeks. PTSD symptoms will be measured again two months after the third MDMA session.

Participants who received placebo and complete the final evaluation two months after the second experimental procedure will be given an opportunity to take part in an open-label continuation of the study where they will receive an initial dose of 125 mg MDMA and a supplemental dose of 62.5 mg MDMA in up to three experimental sessions scheduled three to five weeks apart. Participants in this open-label continuation will act as their own controls. The open-label continuation lasts three months and will involve nine more visits with the investigators, including the two experimental sessions.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Posttraumatic Stress Disorder

Intervention

• Drug: 3,4-methylenedioxymethamphetamine (MDMA)
  125 mg and 62.5 mg MDMA
• Drug: lactose (placebo
  two capsules placebo matched in weight with MDMA capsules
• Behavioral: Psychotherapy
  Psychotherapy provided by a team of two co-therapists

Study Arms

• Experimental: 1
  Participants will receive 125 mg MDMA followed 2 to 2.5 hours later by 62.5 mg MDMA during course of each of two day-long psychotherapy sessions plus a third open-label MDMA-assisted session.
  Interventions:

  • Drug: 3,4-methylenedioxymethamphetamine (MDMA)
  • Behavioral: Psychotherapy
• Placebo Comparator: 2
  Participants will receive an initial dose of placebo orally followed 2 to 2.5 hours later by a second dose of placebo during the course of each of two experimental sessions.
  Interventions:

  • Drug: lactose (placebo
  • Behavioral: Psychotherapy

Publications *

• Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R. The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol. 2011 Apr;25(4):439-52. doi: 10.1177/0269881110378371. Epub 2010 Jul 19. Erratum in: J Psychopharmacol. 2011 Jun;25(6):852.
• Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, Michel Y, Brewerton TD, Doblin R. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol. 2013 Jan;27(1):28-39. doi: 10.1177/0269881112456611. Epub 2012 Nov 20.
• 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. Review.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2014): 23
• Original Enrollment (submitted: June 23, 2005): 20
• Actual Study Completion Date: September 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Be diagnosed with chronic PTSD, duration of 5 years or longer resulting from traumatic experience during military service or a victim of crime;

• Have a CAPS score showing moderate to severe PTSD symptoms;

  1. 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.
  2. 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 50 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 study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00090064
• Other Study ID Numbers: MP1
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Multidisciplinary Association for Psychedelic Studies
• Study Sponsor: Multidisciplinary Association for Psychedelic Studies
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael Mithoefer, MD; Private Practice

• PRS Account: Multidisciplinary Association for Psychedelic Studies
• Verification Date: February 2014