Updates related to the US MDMA/PTSD Study MP-1 (completed) can be found below:
MP-1
April 16, 2012
U.S. Proof of Principle Study: Revised Long-Term Follow-Up Paper Submitted to Scientific Journal
On April 16, 2012, Dr. Michael Mithoefer, the lead investigator for our recently completed long-term follow-up of subjects who participated in the initial U.S. proof of principle study, submitted a revised version of the paper in response to comments from reviewers. We’re hopeful the paper will soon be accepted for publication. The long-term follow-up, conducted an average of 3½ years after the last MDMA-assisted psychotherapy session, found that the benefits persisted over time, though a few subjects had relapsed due to new life stressors.
U.S. Proof of Principle Study: Reviewers Respond to Long-Term Follow-Up Paper
On March 27, 2012, reviewers for a scientific journal responded with their comments on the paper describing the results of our long-term follow-up of subjects who participated in our initial U.S. proof of principle study of MDMA-assisted psychotherapy for PTSD. In their comments and feedback, all four reviewers concluded that it was a strong paper that substantially contributed to the existing scientific research on MDMA-assisted psychotherapy for PTSD. We have incorporated the reviewers’ feedback into the paper, which will be resubmitted for publication in the next few days.
The study, conducted by lead investigator Michael Mithoefer, M.D., and Annie Mithoefer, B.S.N., found that the benefits of MDMA-assisted psychotherapy for PTSD persisted for an average of 3½ years after the last treatment. The study found no evidence of harm associated with the administration of MDMA, either immediately following treatment or during the long-term follow-up. These results are even more important than the remarkable results of our initial proof of principle of study as measured at the two-month follow-up, confirming that the benefits of MDMA-assisted psychotherapy persist over time.
U.S. Proof of Principle Study: Results of Long-Term Follow-Up Submitted to Scientific Journal
On February 5, 2012, after extensive work, the lead investigator of our first U.S. study of MDMA-assisted psychotherapy for PTSD and co-authors submitted a paper describing the results of our long-term follow-up of subjects who participated in the flagship study. The paper was submitted to a peer-reviewed scientific journal and is now being reviewed for publication. In the original study, 17 of 21 subjects no longer qualified for a diagnosis of PTSD after treatment with MDMA-assisted psychotherapy. The long-term follow-up, conducted an average of 3.5 years after treatment, demonstrates that these benefits were, on average, maintained over time. Additionally, of the subjects who were seeing a therapist prior to the study, 45% were no longer seeing one at the time of the follow-up survey; and 55% of those who were receiving psychiatric medications prior to the study were no longer taking them. Two subjects who participated in the original study experienced a return of symptoms during the long-term follow-up period and will be offered enrollment in our relapse study of MDMA-assisted psychotherapy for PTSD, where they may receive one additional full-dose MDMA session.
Ethics Board Approves US MDMA/PTSD Relapse Study Protocol
On June 9, 2011, our Institutional Review Board (IRB) approved the protocol for our new “relapse study” of MDMA-assisted psychotherapy for PTSD. The Food and Drug Administration approved the protocol for this study on May 24, but the DEA must now conduct its own review before granting us the license to store and administer the MDMA. On June 14, Clinical Investigator and co-therapist Michael Mithoefer, M.D., submitted the protocol for the relapse study to the DEA. We anticipate that the DEA will approve the study soon, allowing us to schedule the study initiation and begin enrolling subjects.
This study, which will take place in Charleston, SC, is limited to up to three subjects whose PTSD symptoms returned after participating in our flagship Phase 2 clinical trial of MDMA-assisted psychotherapy for PTSD. Over 80% of the subjects in our previous study no longer met criteria for PTSD two months after treatment. These benefits tended to persist over time until our long-term follow-up, conducted an average of 41 months after treatment. However, for several subjects symptoms did eventually return. This relapse study will attempt to determine whether a single additional open-label MDMA-assisted psychotherapy session along with several non-drug psychotherapy sessions can be effective for once again enabling these subjects to be free of a diagnosis of PTSD.
On May 24, 2011, the FDA approved our study of MDMA-assisted psychotherapy for up to three subjects whose PTSD symptoms returned after participating in our flagship Phase 2 clinical trial of MDMA-assisted psychotherapy for PTSD. After participating in our initial study, subjects were interviewed using the Clinician Administered PTSD Scale (CAPS), a diagnostic tool used by psychiatrists and researchers to assess the severity of PTSD symptoms. At the two-month follow-up after treatment, over 80% of subjects no longer met the diagnostic criteria for PTSD. In the long-term follow-up (conducted an average of 41 months after treatment) we found that CAPS scores had declined even further, demonstrating that benefits persisted over time. For several of these subjects, however, some symptoms did eventually return. The new study will be limited to these subjects, and is intended to determine whether a single additional open-label MDMA-assisted psychotherapy session can be effective for eliminating these relapse symptoms.
The FDA approval came just one week after the agency received our protocol submission on May 17—the fastest turnaround we have ever seen for an FDA protocol approval. This expediency could be attributable to the fact that the risks of treatment are low: Eligible subjects have already been through treatment and been shown to tolerate MDMA in a clinical context.
On Dec. 9, 2010, MAPS’ clinical research team submitted our annual report about MAPS’ MDMA/PTSD research to the FDA. Annual reports are designed to give the FDA an overview of completed, ongoing, and planned studies for specific Investigational New Drug (IND) Applications. In our report, which covered all study activity between June 22, 2009, and October 1, 2010, we provided information about enrollment, including the total number of subjects enrolled for each study. Demographic information for all subjects (such as height, weight, race, and cause of PTSD) was included. We also created overview charts of all serious and severe adverse events experienced by the subjects. Although we reported four serious adverse events to the FDA (a fractured clavicle due to auto accident, a fainting episode, a complication due to cancer, and one psychiatric hospitalization), none of them were related to the administration of MDMA.
On Nov. 5, 2010, at the International Society for Traumatic Stress Studies annual conference in Montreal, Michael Mithoefer, M.D., presented findings, in poster form, from the long-term follow portion of MAPS’ first completed MDMA-assisted psychotherapy study. The poster showed overall therapeutic results were sustained over time. Dr. Mithoefer presented the short-term results from the study at the ISTSS conference in 2008. The new poster provides a comprehensive overview of the study, including short-term and long-term data. Dr. Mithoefer and others are preparing a paper about the results of the long-term follow-up to the US pilot study for submission to a peer-reviewed journal.
Database for U.S. MDMA/PTSD Long-Term Follow-Up Study Finalized
MAPS’ clinical research team completed their review of the data from our flagship MDMA/PTSD study. On Nov. 10, the team closed and locked the database, officially bringing the data collection phase of the study to an end. Now that we have the final data set, the research team can analyze the data and write a paper for submission to a peer-reviewed scientific journal. Twenty of 21 subjects from the study successfully completed the long-term follow-up study and, and the review showed that the benefits were maintained over time. This is especially significant because these subjects were all treatment-resistant, meaning they had tried other medicines and therapies without relief. Additionally, of the subjects who were seeing a therapist prior to the experiment, 45% were no longer seeing a therapist at the time of the follow-up survey; and 55% of the subjects who were previously receiving psychiatric medications were no longer taking them.
Preparation of Final Report to FDA on Initial MDMA/PTSD Study
From Sept. 27 to Oct. 1, Clinical Research Associate Berra Yazar-Klosinski, Ph.D. and Clinical Program Manager Amy Emerson were in Charleston, SC, where they archived the research data from our first U.S. MDMA/PTSD pilot study for long-term storage in preparation for any FDA audits. The documents have also been duplicated for security measures in case any were damaged or destroyed.
Berra, Amy, Ilsa Jerome, and the Mithoefers are working on a comprehensive Final Clinical Study Report for the FDA, which is set to be finished and submitted early next year. It will contain detailed information about everything relevant to the study, such as how it was conducted, how we worked with the Institutional Review Board (IRB), how and what we communicated to the FDA and the DEA, and all of the data, both analyzed and in its raw form. The FDA may conduct an independent analysis of the raw data to verify our conclusions. Essentially, “the final report is a pretty wrapped package of the entire clinical trial,” according to Berra.
Paper in Progress About Long-Term Follow-up to First U.S. MDMA/PTSD Study
On Sept. 27, we completed the long-term follow-up study to our initial US MDMA/PTSD pilot study. Our team is now diligently working on preparing a scientific paper about the results. This study demonstrated that treatment benefits were maintained post-treatment. Some subjects improved further and some subjects experienced more PTSD symptoms, with average treatment benefits slightly increasing (getting better) over time. Subjects were interviewed a mean of 40 months after the treatment, so we can conclude treatment benefits were maintained at least 40 months afterward on average. This finding is more important than our initial finding of substantial therapeutic benefits persisting for two months after treatment.
Notably, no subjects reported any harm from participating in the study. Nor did any subject develop a substance abuse problem. Critics of our research expressed concern that giving a drug of potential abuse to PTSD sufferers could result in drug abuse problems. We now have evidence showing that in our initial subjects, this fear did not materialize.
We hope to have the paper finalized by December and submitted to a journal early in 2011. To that end, we’ve enlisted the help of Tim Brewerton, M.D., a statistics expert who has authored numerous journal publications.
Long-term Follow-up of U.S. MDMA/PTSD Pilot Study is Complete
On July 27, 2010, MAPS Deputy Director Valerie Mojeiko and Clinical Research Associate Berra Yaza-Klosinski, Ph.D. completed data collection for the long-term follow-up to our flagship U.S. MDMA-assisted psychotherapy for PTSD study led by Principal Investigator Michael Mithoefer, M.D. and Co-Investigator Ann Mithoefer, B.S.N. in Charleston, SC. Independent rater Mark Wagner, Ph.D., from the College of Medicine, Department of Neurology, collected Clinician-Administered PTSD Scale (CAPS) measurements from 17 of the 20 subjects who received treatment. All 20 subjects filled out a questionnaire developed internally to assess long-term effects. The average length of time between the final experimental treatment session and the follow-up data collection was three and a half years. Preliminary analysis of the results suggests the benefits of the treatment were maintained. MAPS’ clinical research volunteers are inputting data into a validated database at the MAPS office in Santa Cruz, CA. After the data is analyzed, Dr. Mithoefer, et al, will write a new paper for submission to a scientific journal around the end of 2010.
Journal of Psychopharmacology publishes paper about MAPS-sponsored U.S. MDMA/PTSD pilot study
The Journal of Psychopharmacology published a paper about the MAPS-sponsored U.S. MDMA/PTSD pilot study.The paper is titled, "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," and is authored by Michael Mithoefer, M.D., Mark Wagner, Ph.D., Ann Mithoefer, B.S.N., Lisa Jerome, Ph.D. and Rick Doblin, Ph.D.
Long-Term Follow-Up of U.S. MDMA/PTSD Pilot Study Nears Completion
Our long-term follow-up to our flagship study of MDMA-assisted psychotherapy for the treatment of PTSD, which has been taking place in Charleston, SC, is coming close to completion. All that remains is for the researchers, led by Principal Investigators Michael Mithoefer, M.D. and co-therapist Ann Mithoefer, B.S.N., to collect follow-up information from a few more subjects. Weve already obtained long-term follow-up data from 16 of the 20 subjects, at an average of about 3 years after their final experimental session. The results so far are encouraging.
View As Single Entry > June 20, 2010 International Federation of Psychotherapy Congress in Lucern, Switzerland hosts Mithoefers, Gasser, Oehen, and Passie
From June 16-19, the International Federation of Psychotherapy convened a Congress in Lucerne, Switzerland. As a sign of the growing acceptance of psychedelic psychotherapy research, this mainstream psychotherapy conference had a seminar devoted to the topic. From the U.S., MAPS sent researchers Michael Mithoefer M.D. and Annie Mithoefer, B.S.N. to present information from our U.S. MDMA/PTSD study. MAPS also brought Swiss MDMA/PTSD researchers Peter Oehen, M.D. and Verena Widmer, R.N. and Swiss LSD/end-of-life researcher Peter Gasser, M.D. Also on the panel was renowned German psychedelic researcher Torsten Passie, M.D. This was the first presentation about new data from psychedelic psychotherapy research to a mainstream psychotherapy conference in over 35 years.
Out of about 800 attendees at the conference, approximately 50 people crowded the room for the two-hour panel. According to MAPS Executive Director Rick Doblin, Ph.D. who also attended the conference, the session on psychedelic research was remarkable because it wasnt remarkable it was a mainstream psychotherapy conference that happened to have a panel on psychedelic psychotherapy research. There were no protestors or vocal dissenters. The promising results were taken seriously and our call for expanding research wasnt even considered controversial.
During the trip to Switzerland, MAPS supporter and friend Vanja Palmers hosted Rick and the Mithoefers at his home in Lucerne, only several blocks from the conference center.
U.S. MDMA/PTSD Paper Revised and Resubmitted; Long-Term Follow-Up Study Continues
On Sunday May 9, a manuscript about our flagship U.S. MDMA/PTSD pilot study was resubmitted to a peer-reviewed journal after receiving initial responses to the original submission from four reviewers. We should learn in the next several weeks if this version of the paper, or a slightly modified version, will be accepted for publication. If so, it will be cause for major celebration since this would become the first published paper about a completed study of MDMA-assisted psychotherapy for PTSD. The authors of the paper include Principal Investigator Michael Mithoefer M.D., Mark Wagner, Ph.D., Annie Mithoefer B.S.N., Ilsa Jerome, Ph.D. and Rick Doblin, Ph.D. While our drug development effort does not require the publication of the results of our research in peer-reviewed scientific journals, our public education efforts will be greatly enhanced if we can manage to publish our results.
The long-term follow-up study for this research project is still ongoing, with just a few additional subjects still to be assessed. The remaining data on long-term effects of MDMA-assisted psychotherapy to be collected from the subjects is extremely valuable to the final data analysis and submission to the FDA. Preliminary results from the long-term follow-up are encouraging.
View As Single Entry > May 1, 2010 Second MDMA/PTSD Therapist Training Program, Soliciting More Applicants
From April 7 to 12, Michael Mithoefer, M.D., and Annie Mithoefer B.S.N. led an MDMA/PTSD therapist-training program with eight attendees in South Carolina. The group reviewed our treatment manual in order to learn how to conduct therapy in accordance with our treatment method. A major portion of the training was reviewing videos from past experimental psychotherapy sessions from our first U.S. MDMA/PTSD study. This training program, and those planned for the future, will be used to teach applicants to conduct our future research projects. Applicants who complete the non-drug training program and satisfy screening criteria may have the opportunity to take MDMA in a therapeutic setting as part of our Phase 1 study to investigate the effects of MDMA on healthy volunteers; this study is also designed to give therapists subjective experiences of what MDMA therapy is like.
We are anticipating that we will need more therapist teams in approximately three years, if and when we start our Phase 3 studies. Since the training program can take a long time, we are currently soliciting more applications from qualified therapists interested in conducting clinical research with MAPS. If interested please contact Berra Yazar-Klosinski, Ph.D. at: .(JavaScript must be enabled to view this email address)
MAPS Clinical Plan for End-of-Phase 2 Meeting with the U.S. FDA to Develop MDMA as a Prescription Medicine for PTSD
On Monday, March 22, MAPS received final approval from our Institutional Review Board (IRB) to move forward with our new MDMA/PTSD study. Michael Mithoefer, M.D. and Annie Mithoefer, BSN will conduct this new study in Charleston, South Carolina. They both ran the previous MAPS-sponsored US MDMA/PTSD study, which successfully demonstrated both safety and efficacy in treating treatment-resistant PTSD patients with MDMA-assisted psychotherapy and produced statistically and clinically significant findings. A scientific paper about the results is currently being evaluated for publication by a journal.
In the Mithoefers previous study of 21 people suffering from treatment-resistant PTSD, only two of the subjects were military veterans, and all but three of the subjects were women who were survivors of sexual assault or childhood sexual abuse. This new study will be conducted entirely with U.S. war veterans with PTSD. This study will help us determine if our treatment can be applied to people with PTSD from different causes or if our treatment itself needs to be modified to match the cause of the PTSD. Unlike the Mithoefers first study, which only had two groups (inactive placebo and full-dose MDMA), this study will compare three doses of MDMA—30 mg, 75 mg, and 125 mg, in an effort to enhance the double-blind. Most importantly, we will be testing what may become the protocol design that will be used in our large-scale, multi-site Phase 3 studies.
Because the Mithoefers previous study was the first study of its kind, we needed to establish a baseline of potential side effects of psychotherapy alone in people with PTSD who were treated with a placebo. People who received nothing but a placebo still reported side effects, so it was important that we have a pure placebo control, otherwise any of these side effects could be attributed to the MDMA. The rightful criticism of our first study, and the primary critique of the data so far, has been that it wasnt effectively double-blind because the subjects could easily tell if they were given the active drug or a placebo. That criticism will be addressed in the Mithoefers new study, and an active placebo of low-dose MDMA is being used in our other studies abroad—in Israel, Switzerland, Canada, Spain, and Jordan.
The Mithoefers new study will be a methodological response to the primary critique of our first study. In addition to our research in the United States, MAPS is currently engaged in MDMA/PTSD studies in several other countries around the world—Switzerland, Israel, and soon Canada, Jordan, and Spain. All of these studies are intended to prepare us for an End-of-Phase 2 meeting with the FDA, the purpose of which is to come to agreement with the FDA on the design of the large-scale Phase 3 studies that we want to conduct. At the meeting, we will review our data, and explain the methodological and statistical considerations in our proposed design of a large-scale, multi-site, Phase 3 safety and efficacy trial. Once weve come to an agreement on the design of our Phase 3 studies, if we get good results and show safety and efficacy, then the FDA will approve our application to market MDMA for PTSD patients.
The Mithoefers new study in veterans has been approved by both the FDA and the IRB, so now were waiting for the DEA to facilitate the licensing and transfer of the MDMA so we can begin this study. Michael and Annie Mithoefer will be giving a presentation about their work at the upcoming MAPS-sponsored Psychedelic Science conference in San Jose next month, and their workshop about MDMA and PTSD is already almost filled to capacity.
Through extensive discussions and cooperation with the FDA, the protocol meets two goals at once. On the one hand, it is designed as a Phase 1 randomized, placebo-controlled, double-blind study of the psychological effects of MDMA on healthy volunteers. On the other hand, enrollment is limited to subjects who are participating in our MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) therapist training program. The final draft of the protocol meets both the FDAs goals and MAPS goals. Now that we have the FDAs “may proceed” letter, we will be seeking approval from an Institutional Review Board (IRB).
We will be measuring the psychological effects of MDMA on “healthy normals” as contrasted with our international series of Phase 2 pilot studies evaluating MDMA-assisted psychotherapy in people who have treatment-resistant posttraumatic stress disorder (PTSD). We will employ some psychological measures that have not yet been used in an MDMA research project as well as some that we have used before. The psychological measures include measuring mood with the Profile of Mood States, personality with the Neuroticism-Extroversion-Openness (NEO) Inventory, interpersonal closeness with a nonverbal (visual analog) self-report measure, psychological symptoms with the Brief Symptom Inventory (BSI), and suicidality with the Columbia Suicide Severity Rating Scale (C-SSRS). As a crossover study, subjects will get placebo on one occasion and MDMA on the other.
The FDAs “may proceed letter marks a major turning point for MAPS. We now have the ability to offer one full-dose MDMA-assisted psychotherapy session to therapists who are preparing to conduct Phase 2 and Phase 3 MDMA/PTSD studies for MAPS. During these studies we will be gathering information about the psychological dynamics of MDMA-assisted psychotherapy. We believe that this new protocol substantially increases the chances that we will successfully conduct the next step in our mission: a Phase 3 multi-site pilot study with 20-30 co-therapist teams.
US MDMA/PTSD Pilot Study Manuscript Rejected by Journal
We learned a few weeks ago that the Archives of General Psychiatry rejected our manuscript about MAPS flagship U.S. MDMA/PTSD pilot study. While we are very disappointed that the paper was rejected, we knew that it would be a long shot since this is the leading journal in the field of psychiatry and it has a conservative reputation. While some of the reviewers comments were quite insightful, other comments about MDMAs safety and the study design were simply mistaken. We are in the process of taking the insightful comments into consideration and rewriting the paper for submission to a new journal.
MDMA Data Analysis Nearly Ready for FDA Submission
On May 29, 2009, we will submit a preliminary dataset to FDA containing basic safety information from our US MDMA-assisted psychotherapy pilot study. Over the past several months MAPS Clinical Research Associate Valerie Mojeiko has been working diligently with a team of consultants from the pharmaceutical industry to prepare this preliminary data set, and to develop a streamlined collection of standard operating procedures to use in future data sets. This submission to FDA is the first of several data reports from our first pilot study and will provide the scientific justification for future protocols that we will submit to FDA.
MDMA/PTSD Paper Completed and Sent for Friendly Review
MAPS is pleased to share that after months of work, our research team has completed a scientific paper that reports the remarkable results from our US MDMA/PTSD pilot study. Dr Michael Mithoefer, Annie Mithoefer, BSN, Ilsa Jerome, PhD, Mark Wagner, PhD, and MAPS President Rick Doblin, PhD, with assistance from statistician Yvonne Michel PhD, spent tremendous effort preparing the paper for submission to a peer-reviewed journal. We have now sent out the paper to several friendly reviewers for informal critique. We will incorporate the feedback we get from these reviewers and then submit the paper to a peer-reviewed scientific journal. This is a major milestone for MAPS and the legitimacy of psychedelic psychotherapy. When the paper is published in a peer-reviewed journal, MDMA-assisted psychotherapy will gain credibility among the scientific community and subsequently the general population. We have not yet released the paper to our readership, but keep checking back on our monthly email update to read about the results of this historic study.
MAPS-Sponsored MDMA/PTSD Co-Therapists will Travel to MAPS Training Seminar in Austria, June 25 July 1, 2009:
MAPS has finalized plans and chosen a time and location for our first five-day MDMA/PTSD therapist training retreat for MAPS-sponsored researchers. The event will take place at the end of June in the Austrian mountains, where its off-season, reasonably priced, and more-or-less centrally located for therapist teams and MAPS staff coming together from the US, Canada, Switzerland, Spain, Israel, and Jordan.
Michael Mithoefer, MD and Annie Mithoefer, BSN, the co-therapist team from MAPS successfully completed U.S. MDMA/PTSD pilot study, will share techniques and results with the other therapists. June May Ruse, PhD, will present the principles in our treatment manual, which she is developing with feedback from our research teams.
The therapeutic outcomes in our US study were remarkable. In order to increase the chances that other co-therapist teams can replicate these results in MAPS other studies, Michael and Annie will present videotapes of their sessions and lead discussions about lessons theyve learned. The Swiss and Israeli co-therapist teams, who have treated some subjects but havent completed their studies yet, will also lead presentations about their results and methods. We will also discuss cultural differences, research methodology, and other treatments for PTSD and their similarities and differences from MDMA-assisted psychotherapy. We will have time for a breathwork session and opportunities for informal sharing. MAPS staff will be creating podcasts and writing blogs from the training seminar to keep our members and other interested parties informed of the valuable information that comes from it.
This private retreat will also serve to inform MAPS 2010 conference, which is open to medical professionals, MAPS members and the general public.
MAPS US MDMA/PTSD researchers, including Michael Mithoefer MD, Annie Mithoefer BSN, Mark Wagner PhD, Ilsa Jerome PhD, and Rick Doblin PhD, are preparing a paper about our U.S. pilot study of MDMA-assisted psychotherapy for the treatment of posttraumatic stress disorder, which has obtained impressive results The first draft of the paper is close to being sent out to friendly reviewers for initial scrutiny. We will submit the paper to a scientific journal after we respond to the critiques from colleagues and experts. The team is working diligently on the paper to ensure that we provide the eventual reviewers with a compelling submission. MAPS is very excited about the paper; now that we have run the data analysis our research results are really impressive.
Flagship US MDMA/PTSD Study Final Monitoring Visit:
On January 20-22, MAPS’ clinical research monitoring team, Valerie Mojeiko and Josh Sonstroem, went to Charleston, South Carolina to conduct a closeout visit for MAPS’ flagship US MDMA/PTSD study. The data from this study is now ready to be submitted to FDA.
With this ending also comes the beginning of the “long-term follow up” extension to this study. During this extension, subjects who were enrolled in the original study will be retested on primary outcome variables one year or more after completion. In the initial study, the last measurement of PTSD severity was taken two months after the last experimental session. Since this study took over four years to conduct, some of the data from the long-term follow-up will be from subjects who were treated over four years ago. The value of the long-term follow-up study will be substantially enhanced as a result of the extra length of time since treatment for most of the subjects. MAPS is pleased to have the help of volunteers Scott Martin MD and Mili Ballard to coordinate this long-term follow-up study.
On December 18, all the documents for our Canadian study of MDMA-assisted psychotherapy in the treatment of people with Posttraumatic Stress Disorder (PTSD) were submitted to Health Canada (Canada’s version of the FDA). We’ve already obtained approval of our protocol and informed consent from a Canadian Institutional Review Board. We should receive a reply from Health Canada within 30 days of our submission.
This is going to be a study with 12 subjects, similar in design to the recently completed US MDMA/PTSD study. Our main purpose for this particular study is to see if we can replicate the results of the US study. The budget for this study is $250,000, all of which remains to be raised.
MAPS Releases Year-End MDMA Literature Review: As part of our ongoing clinical research responsibilities, MAPS reviews all of the MDMA- related articles published in scientific peer-reviewed journals to determine whether we need to modify our risk/benefit analysis for our clinical studies. We have now completed our review of the scientific literature published between December 2007 and November 2008 and submitted the review to the Institutional Review Board (IRB) that oversees our US MDMA/PTSD study. Nothing in the review changes our risk/benefit analysis regarding our research in human subjects. This review—along with all previous reviews—are compiled by MAPS Research Specialist Ilsa Jerome, and are posted on the MAPS website at: www.maps.org/mdma/protocol/litreview.html
Newly Revised MDMA/PTSD Treatment Manual Now Online: MAPS Researchers Michael Mithoefer MD, Annie Mithoefer BSN, and June May Ruse PhD, have created a revised version of MAPS MDMA/PTSD treatment manual. The new version of the manual builds on a previous manual from 2005, and includes lessons learned from our recently completed US MDMA/PTSD pilot study. The team of researchers reviewed many hours of videotapes of the therapy sessions with the aim of finding clear examples of the key elements of the therapeutic method. The manual will be continually revised as we identify best practices and gather data to link methods to outcomes. The manual, will also be used to develop measurement tools for identifying key elements of the therapeutic method.
The treatment manual, selected excerpts of the videotapes, and the measurement scales of the key elements of our therapeutic method, will form the core of our therapist training program for the male/female co-therapist teams who will conduct MAPS Phase 3 multi-site studies. We anticipate sponsoring studies in 20-30 different locations across the US, Europe, Israel and Jordan.
A family foundation that wishes to remain anonymous donated $50,000 to MAPS for our US MDMA/PTSD research. The foundation had generously supported our US MDMA/PTSD study during the early stages of the research – giving substantial donations that played a crucial role in launching this project.
In addition, long-time MAPS supporter Tim Butcher (profiled in MAPS Bulletin article), is donating $17,000 to our US MDMA/PTSD study, with an initial donation of $5000 and $1,000 a month for the next year.
MAPS Researcher Michael Mithoefer, MD expressed his appreciation to these donors and noted, “Because MDMA can’t be patented these studies are not going to be funded by for-profit pharmaceutical companies. So far we have not been able to get government funding, and I don’t expect that to change in the foreseeable future. Contributions like yours are making it possible for us to complete the analysis and dissemination of our results and to now move forward with development of a training program, new protocols and teams of therapists and other researchers to perform a multi-center study. We are continually encouraged and deeply touched by the level of support MAPS is receiving for this work. The fact that this research can be accomplished by a small non-profit organization supported by a community of people who recognize the healing potential of MDMA and the importance of rational government policy based on science is quite extraordinary. This effort has already made a huge difference in the lives of the people with severe PTSD who participated in the study. I especially want to communicate that fact to you because you are playing a significant role in making it possible.”
From October 6-10, 2008, Michael Mithoefer MD, Annie Mithoefer BSN, and June May Ruse PhD, worked on the MDMA/PTSD treatment manual. This was their second week working together in person, with a third week anticipated in December or January. They have reviewed many hours of videotapes of therapy sessions from Michael and Annie’s recently completed US MDMA/PTSD pilot study, with the aim of finding clear examples of the key elements of the therapeutic method. They intend to develop scales of approximately ten key elements of the therapeutic method. These scales would then be used by raters to evaluate researchers/therapists’ adherence to our specific therapeutic method.
The treatment manual, selected excerpts of the videotapes, and the scales of the key elements of our therapeutic method, will form the core of our therapist training program for the male/female co-therapist teams who will conduct MAPS’ Phase 3 multi-site studies. We anticipate sponsoring studies in 20-30 different locations across the US, Europe, Israel and Jordan.
On October 7, 2008, MAPS sent a draft of a protocol for a MAPS-sponsored MDMA/PSTD pilot study to Royal Jordanian Military psychiatrist Nasser Shuriquie. Dr Shuriquie needs to show the protocol to other medical officials to gauge whether there is sufficient support to justify submitting a final draft of the protocol to a Jordanian Ethics Committee and the Jordanian Ministry of Health. This version of our protocol differs from other pilot studies in several ways. It begins with a three-subject open label run-in in which both the subjects and the therapists know that MDMA is being administered. In this way, the therapist gets a chance to practice our therapeutic technique and become familiar with the therapeutic process before administering MDMA or placebo to other subjects in the context of a placebo-controlled, randomized, double-blind study. We believe that it is important for the therapist to get a chance to become comfortable with the procedure prior to starting a controlled study. The remainder of the protocol is a nine-person study, where six subjects receive three sessions of full-dose MDMA, 125 mg followed one-and-a-half to two-and-a-half hours later by 62.5 mg. Three subjects would receive active placebo, in this case 40 mg followed 1.5-2.5 hours later by 20 mg. Our Swiss, Israeli and Canadian MDMA/PTSD pilot studies are using 25 mg as the active placebo while our US study used an inactive placebo.
The Sunday Times (London) recently published "Ecstasy is the Key to Treating PTSD," an in-depth piece on MDMA-assisted psychotherapy in people with PTSD, focusing on Dr. Mithoefer's MAPS-supported study and featuring quotes from MAPS president Rick Doblin and British psychiatrist Ben Sessa.
This letter by Krebs and Johansen commenting on and questioning the findings of the prospective study of cognitive function in ecstasy users is now published in the Archives of General Psychiatry. The letter addresses issues relating to the nature of the test score differences, the existence of long-term retest effects, participant durg use history and effects of anxiety arising from stereotype threat. Schilt and colleagues’ reply appears alongside the letter. They respond to questions concerning retest learning effects and re-analyze data with respect to drug use history. Krebs and Johansen are conducting an examination of psychological defense mechanisms in experimental sessions from Mithoefer’s randomized, placebo-controlled study of MDMA-assisted psychotherapy in people with PTSD.
Washington Post magazine published an article (MAPS PDF Permalink) featured as the cover story about MAPS’ and Dr. Michael Mithoefer’s MDMA-PTSD research entitled "Peace Drug". This article is overall positive with one minor mistake--the idea of MDMA being prescribed only by specially trained therapists in psychedelic clinics is attributed to Dr. Michael Mithoefer when it should have been attributed to Rick Doblin Ph.D.’s dissertation. This article is unique as it is the first time that a reporter has been allowed to interview a research participant from this historic study. You can read the comments about this article here.
MAPS communications director Jag Davies conducted a podcast interview (mp3) with Dr. Michael Mithoefer, in which Dr. Mithoefer discusses the details of his study, his working relationship with wife and co-therapist Annie Mithoefer, and his musings on the psychological mechanisms involved in MDMA-assisted psychotherapy.
Sixteen out of twenty subjects have completed the double-blind protocol in Dr. Michael Mithoefer’s flagship MAPS-sponsored FDA Phase 2 study evaluating MDMA-assisted psychotherapy for subjects with treatment-resistant post-traumatic stress disorder (PTSD). Three new subjects have been enrolled, two of which are close to completion of the first stage of the protocol. One of these new subjects is a US military veteran whose trauma occurred during combat in Iraq.
Last month, MAPS and Dr. Mithoefer submitted a protocol amendment to FDA, seeking approval to treat a 21st subject, also a US veteran with PTSD from the Iraq War. We need FDA permission to deviate from our inclusion criteria that requires all PTSD subjects to be treatment-failures from both drug and non-drug treatments. The FDA has accepted our request, which we have just submitted to our institutional review board (IRB) for final review.
American Medical News published a feature article entitled "Altered Perceptions: Good Outcomes from 'Club Drugs'"? MAPS President Rick Doblin, PhD, and researchers Michael Mithoefer, MD, John Halpern, MD, and Charles Grob, MD, are quoted. American Medical News is a weekly newspaper for physicians published by the American Medical Association that is ciculated to over 230,000 physicians and health policy regulators.
MAPS and Dr. Mithoefer submitted a protocol amendment to FDA, seeking approval to treat a 21st subject, a US veteran with PTSD from the Iraq War. We need FDA permission to deviate from our inclusion criteria that requires all PTSD subjects to be treatment-failures from both drug and non-drug treatments. The request to include a subject who is not a treatment-failure is due to the sad fact that this veteran, like several others with whom we have spoken, has been diagnosed with PTSD but has never been offered treatment by the military. We expect to hear from FDA in a few weeks. Michael Mithoefer, MD, and Annie Mithoefer, BSN, have enrolled 18 out of 20 subjects in their MAPS-sponsored study evaluating MDMA-assisted psychotherapy for subjects with chronic PTSD. Another two potential subjects are currently in the screening process. The completion of MAPS’ flagship FDA Phase 2 clinical research study is now in sight.
Yesterday, June 26, the 17th subject out of 20 completed the first experimental session in Dr. Michael Mithoefer’s MAPS-sponsored study evaluating MDMA-assisted psychotherapy for subjects with treatment-resistant post traumatic stress disorder (PTSD). We are still actively seeking to enroll in the study at least two US veterans with PTSD from the Iraq or Afghanistan wars.
This Phase II clinical study is the first-ever FDA-approved human study evaluating MDMA’s therapeutic applications. Efficacy data is extremely promising so far, making a strong case for continuing research into FDA Phase III studies.
We have learned that the data being generated from the Swiss and Israeli MAPS-sponsored studies will be accepted by the US FDA.
Although these protocols do not need to be approved by the FDA to be conducted in their home countries (they have already been approved by their home country’s regulatory agency equivalent to FDA and by local ethics committees), FDA review and approval enables us to submit to FDA the data from these two studies as part of MAPS’ Investigational New Drug (IND) application for MDMA-assisted psychotherapy in the treatment of PTSD. The data from these studies will be used to help negotiate with FDA regarding the design of larger Phase 3 studies intended to gather data to determine whether or not MDMA meets the requirements necessary to be approved as a legal prescription medicine.
To learn more about the MAPS-sponsored study in Israel evaluating MDMA-assisted psychotherapy for subjects with war- and terrorism-related PTSD, the protocol is posted on the MAPS Web site.
To learn more about the MAPS-sponsored MDMA/PTSD study in Switzerland, the protocol is also posted on the MAPS Web site.
Dr. Michael and Annie Mithoefer, the co-therapists for MAPS’ landmark US MDMA/PTSD study, were in Norway recently attending a workshop by Dr. Edna Foa, an internationally-recognized expert in the treatment of PTSD. The workshop was organized by Pal-Orjan Johansen, a Ph.D. candidate at the Trondheim Psychotherapy Research Program, Department of Psychology, The Norwegian University of Science and Technology, and Teri Krebs, B.S., Program in Neuroscience, Boston University.
While in Norway, Dr. Michael and Annie Mithoefer were also able to work with Pal and Teri, who are conducting a MAPS-sponsored study reviewing audio and video recordings and transcripts of subjects in the Mithoefer’s MDMA/PTSD research, in order to code and compare the psychological defense mechanisms used in both non-drug therapy sessions and in the experimental MDMA-assisted therapy sessions. This study is designed to identify process variables that may help explain how MDMA can be a useful adjunct to psychotherapy.
Dr. Michael and Annie Mithoefer were also able to discuss with Pal and Teri their MAPS-sponsored project using the internet to search for reports of people with Asperger’s (a form of high-functioning autism) who have found MDMA to be helpful in their learning to cope more effectively in social situations. If we do find at least a handful of such reports, this could become another area of research, if funding becomes available.
Drs. Mithoefer, Peter Oehen and Franz Vollenweider, will be presenting their MDMA/PTSD work at the European Conference on Traumatic Stress in Croatia next month.
Dr. Michael and Annie Mithoefer, the co-therapists for MAPS’ landmark US MDMA/PTSD study, were in Norway recently attending a workshop by Dr. Edna Foa, an internationally-recognized expert in the treatment of PTSD. The workshop was organized by Pal-Orjan Johansen, a Ph.D. candidate at the Trondheim Psychotherapy Research Program, Department of Psychology, The Norwegian University of Science and Technology, and Teri Krebs, B.S., Program in Neuroscience, Boston University.
While in Norway, Dr. Michael and Annie Mithoefer were also able to work with Pal and Teri, who are conducting a MAPS-sponsored study reviewing audio and video recordings and transcripts of subjects in the Mithoefer’s MDMA/PTSD research, in order to code and compare the psychological defense mechanisms used in both non-drug therapy sessions and in the experimental MDMA-assisted therapy sessions. This study is designed to identify process variables that may help explain how MDMA can be a useful adjunct to psychotherapy.
Dr. Michael and Annie Mithoefer were also able to discuss with Pal and Teri their MAPS-sponsored project using the internet to search for reports of people with Asperger’s (a form of high-functioning autism) who have found MDMA to be helpful in their learning to cope more effectively in social situations. If we do find at least a handful of such reports, this could become another area of research, if funding becomes available.
Drs. Mithoefer, Peter Oehen and Franz Vollenweider, will be presenting their MDMA/PTSD work at the European Conference on Traumatic Stress in Croatia next month.
An encouraging advancement is that we may be close to enrolling the final five subjects needed to complete Dr. Mithoefer’s study. We’ve focused more attention on recruitment with ads on various psychedelic-related websites and websites for PTSD support groups and currently have more than five subjects going through the screening process. Two of these potential subjects are Iraq War veterans. Efficacy data at this stage is promising, so far making a strong case for continuing the research into FDA Phase 3 studies.
After several years of effort, three rejections, and an appeal, the Institutional Review Board (IRB) for Dr. Michael Mithoefer’s flagship MAPS-sponsored US MDMA/PTSD study approved an amendment to the study’s protocol. The IRB decided that it will not object to subjects speaking with the media and/or documentary filmmakers following completion of each subject’s participation in the study. The IRB originally insisted that patients not speak with the media even after the entire study is complete. After years of careful consideration, the IRB has now determined that it has no jurisdiction to control subjects’ decisions about whether or not to speak to the media. Now that the media policy has been resolved, we are ready to move forward with our 12-month follow-up evaluations, which the IRB has previously approved.
The Data Safety Review Board (DSMB) for Dr. Michael Mithoefer’s MAPS-sponsored FDA Phase 2 pilot study evaluating MDMA-assisted psychotherapy for subjects with posttraumatic stress disorder (PTSD) met in late January for its final review, now that 15 out of 20 subjects have completed the experimental treatment. The DSMB recommended that the study continue without modification. Ironically, the DSMB’s only safety concern was that those subjects who received the placebo might see a substantial increase in PTSD symptoms after tapering off of psychiatric medications. The DSMB is comprised of an M.D., a Psy.D. and a Pharm.D. not otherwise involved in the study. Efficacy data at this stage is promising, so far making a strong case for continuing the research into FDA Phase 3 studies. We’re already looking beyond the next five subjects and the completion of this initial study, to future research protocols.
Slate published a positive description of MAPS' MDMA drug development efforts in a front page article entitled "What a Long, Strange Trip It's Been: Ecstasy, the New Prescription Drug?"
From January 3-6, 2007, MAPS’ clinical research team (Amy Emerson, Valerie Mojeiko, and Josh Sonstroem) was in Charleston, SC, conducting a monitoring inspection of Dr. Michael Mithoefer’s MAPS-sponsored IRB-, DEA-, and US FDA-approved MDMA/PTSD study. On January 5, the 15th subject participated in her third and final experimental MDMA-assisted psychotherapy session. On January 6, MAPS President Rick Doblin visited Charleston to meet with Dr. Michael and Annie Mithoefer and MAPS’ clinical research team to review the data, which looks very promising. An additional $125,000 will be required to complete this study.
Dr. Michael Mithoefer treated the 13th subject with a third MDMA-assisted psychotherapy session today in his MAPS-sponsored FDA Phase II pilot study of MDMA-assisted psychotherapy for individuals with treatment-resistant post-traumatic stress disorder (PTSD). The 16th patient out of 20 was also just screened and admitted to the study earlier this week.
Dr. Michael and Annie Mithoefer treated the 13th subject with the second experimental MDMA/placebo session in their MAPS-sponsored MDMA/PTSD trial today. Dr. Mithoefer described it as “impressive.”
Dr. Michael Mithoefer initiated the first experimental MDMA-assisted psychotherapy session with the 13th subject out of 20 in his MAPS-sponsored FDA Phase II pilot study. This subject was the first to receive supplemental dosing of half the initial amount of MDMA administered 2 to 2.5 hours after the initial dose in order to prolong the plateau of MDMA’s therapeutic effectiveness, a change recently approved by Dr. Mithoefer’s Istitutional Review Board (IRB), the Food and Drug Administration (FDA), and the Data Safety Monitoring Board (DSMB). The supplemental dose did not seem to intensify the already strongly therapeutic experience but it did prolong the period of maximum therapeutic effect for at least 90 minutes. This appeared to be very useful. We were also happy to see that, as expected, there was no problem with vital signs.
Dr. Michael Mithoefer has received Institutional Review Board (IRB) approval for several key changes that FDA had recently approved to his MAPS-sponsored study evaluating MDMA-assisted psychotherapy as a treatment for PTSD. The changes include (1) adding a third experimental session to the two that are currently included in the protocol to test whether a third session adds significantly to the therapeutic process, (2) providing supplemental dosing of half the initial amount of MDMA administered 2 to 2.5 hours after the initial dose in order to prolong the plateau of MDMA’s therapeutic effectiveness, and (3) doing without an ER doctor on standby in the next room since Dr. Mithoefer has become a board-certified ER doctor as well as a board-certified psychiatrist. Now that the Data Safety Monitoring Board (DSMB), FDA, and IRB have all approved these changes to our protocol, they will be implemented for the study’s remaining eight subjects.
The Boston Globe published "A Good Death", an article that discussess the resurgence of interest in studying MDMA and psychedelic drugs to help people with cancer deal with anxiety and pain. The piece describes research MAPS helped design and locate funding for that will look at the potential therapeutic benefits of MDMA in people who are anxious as a result of advanced stage cancer. The latest MAPS Bulletin contains an article about the woman described in this article who used MDMA to treat cancer-related pain and anxiety. A PDF of the this piece is now available.
MAPS’ Data Safety Monitoring Board (DSMB) met to review records for the six new subjects who have enrolled since their last meeting in Dr. Michael Mithoefer’s study evaluating MDMA-assisted psychotherapy as a treatment for PTSD. With data from a total of eleven subjects before them, the DSMB reported that they did not have any concerns about the safety of the study, and recommended that it continue without modification. The DSMB is comprised of an M.D., a Psy.D., and a Pharm.D. not otherwise involved in the study. Dr. Mithoefer has successfully treated 11 out of an eventual 20 subjects, and is currently treating the twelfth. The DSMB also reviewed and approved three protocol changes that Dr. Mithoefer and MAPS will initially submit to FDA and then, if approved, to our Institutional Review Board (IRB). Dr. Mithoefer is seeking permission to: 1) Increase the number of MDMA experimental sessions from two to three, to evaluate whether this extra session will enable subjects to make more therapeutic progress. 2) Administer supplemental doses of 1/2 the initial dose of MDMA 2 to 2 1/2 hours after the initial dose, in order to prolong the relatively short plateau of MDMA’s full therapeutic effectiveness. 3) Since Dr. Mithoefer has recently renewed his Board certification in ER medicine, we have asked to do without the additional Board-certified ER doctor sitting in the next room. In comparison, Dr. Peter Oehen’s study in Switzerland has been designed and approved for three MDMA experimental sessions and the use of supplemental doses. Dr. Kotler’s study in Israel has been designed and approved with supplemental dosing but just two MDMA experimental sessions.
The 25.01.06 article, "Mental scars of Iraq conflict participants exposed" by Kim Sengupta, reported that the US military was giving soldiers fighting the Iraq war "Ecstasy tablets to help free them of flashbacks and recurring nightmares," after the FDA "authorised the issuing of the MDMA drug to Iraq veterans after successful initial research carried out at a facility in South Carolina." This is not quite accurate. Its true that the initial MDMA research in South Carolina is generating very promising results, and the FDA did authorize the expansion of the research to include soldiers. However, no soldiers have yet been treated and the initial study has not been completed. Much larger studies will be needed before MDMA is ever a prescription medication. Research with MDMA for war and terrorism-related posttraumatic stress disorder (PTSD) has been approved in Israel and MDMA/PTSD research is soon to be approved in Switzerland. If approved as a treatment, MDMA will never be issued as tablets directly to soldiers or other patients. MDMA is not a standard pharmacological treatment. MDMA is intended to be used under direct supervision of a therapist as part of MDMA-assisted psychotherapy.
Rick Doblin, Ph.D.
President, MAPS (http://www.maps.org)
MAPS is the non-profit organization that is sponsoring
the research into MDMA-assisted psychotherapy
Dr. Michael Mithoefer, Principal Investigator of the MAPS-sponsored MDMA/PTSD psychotherapy study in Charleston, South Carolina, filed an Annual Status Report with his Institutional Review Board (IRB). There have been no drug-related Serious Adverse Events (SAEs) and the results on treatment efficacy are promising.
MAPS received word that the Israeli Ministry of Health has approved our MDMA/PTSD pilot study!! One condition was that the Israeli Anti-Drug Authority write a letter formally indicating support for the protocol, which the Israeli Anti-Drug Authority has done. Now we need to bring the Israeli therapeutic team to the US to observe an MDMA/PTSD session conducted by Dr. Michael and Annie Mithoefer and we need to bring MAPS Clinical Research Monitoring Team to Israel, to set up the Case Report Forms and the Standard Operating Procedures (SOPs). Plus we need to arrange to export MDMA to Israel for the study. Once these steps have all been accomplished, the study itself can begin enrolling subjects. We’re anticipating that the study can begin in March 2006.
MAPS donated $15,046.25 to McLean Hospital,
affiliated with Harvard Medical School. The donation is to enable
Dr. John Halpern to develop a protocol for the use of MDMA-assisted
psychotherapy in the treatment of anxiety and depression in end-stage
cancer patients, and for work related to obtaining approval for
the study from the McLean Institutional Review Board (IRB) and the
FDA. The donation will support a portion of Dr. Halpern’s time from
now until the end of December 2003.
If this project is approved, it will represent the first psychedelic
research at Harvard since 1965 and will signal the beginning of
the post-Leary era.
A pilot study of MDMA therapy in
the treatment of PTSD has been approved and will be the first formal
therapy study with MDMA ever conducted. (Read
current update. MAPS has pledged $54,000 for this study; we
have raised $23,000 and are seeking additional contributions.
Miller-Mccune "