MAPS Bulletin Summer 2020: Vol. 30, No. 2
Treating PTSD with MDMA-Assisted Therapy
Interim Analysis Shows At Least 90% Chance of Statistically Significant Difference in PTSD Symptoms after MDMA-Assisted Therapy
- An independent Data Monitoring Committee has reviewed data from MAPS’ ongoing Phase 3 clinical trial
- The results are the strongest confirmation that an interim analysis can provide
- MAPS and the Psychedelic Science Funders Collaborative have completed the Capstone Campaign to raise the $30 million needed to complete the research and make MDMA a medicine
On May 12, 2020, the non-profit Multidisciplinary Association for Psychedelic Studies (MAPS) announced the results of an interim analysis of the data from the first of its two Phase 3 clinical trials of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD). This is the best-case scenario for an interim analysis, and suggests that MAPS’ research program is on track for approval by the U.S. Food and Drug Administration (FDA).
The analysis was conducted by an independent Data Monitoring Committee, which reviewed the results from the first 60 out of 100 participants. The analysis revealed a 90% or greater probability that the trial will detect statistically significant results when all participants have been treated, and that the trial will not require additional participants beyond the first 100. The interim analysis was approved by the FDA as part of MAPS’ Statistical Analysis Plan approved by the FDA.
The results strongly suggest that the FDA made the right decision in granting MAPS both (1) Breakthrough Therapy Designation for MDMA-assisted psychotherapy for PTSD, which accelerates the clinical trial process and acknowledges MDMA-assisted psychotherapy as a potentially significant advance over currently available treatments for PTSD, and (2) expanded access, which will allow some patients early access to MDMA-assisted psychotherapy for PTSD prior to approval.
Not all interim analyses are successful. For example, in February 2020, Tonix Pharmaceuticals’ Tonmya®, the only other drug granted Breakthrough Therapy Designation by the FDA for PTSD, failed its interim analysis.
“In the pharmaceutical drug development community, this is what you dream about,” says Rick Doblin, Ph.D., MAPS Founder and Executive Director. “The results of the interim analysis of MAPS’ pivotal first Phase 3 trial are the most powerful evidence yet that MDMA-assisted psychotherapy could help transform the lives of people suffering from PTSD. We have trained approximately 70 new therapists to work on Phase 3, so these results also show that the treatment is scalable, eventually to tens of thousands of therapists worldwide.”
To complete this research and make MDMA a legal medicine, MAPS, in collaboration with the Psychedelic Science Funders Collaborative (PSFC), recently accomplished the $30 million Capstone Campaign.
“Psychedelic medicines show incredible promise for treating a range of mental health conditions, but psychedelic research has been underfunded for decades,” says Joe Green, Co-Founder and President of PSFC. “This first look at data from the first-ever Phase 3 trial of a psychedelic-assisted therapy only makes us more confident that we’re standing on the cusp of a breakthrough. The approval of MDMA-assisted psychotherapy would be a catalytic event that brings psychedelic medicine into the mainstream. That’s why we are excited to partner with MAPS in creating the Capstone Campaign to bring this research across the finish line.”
MAPS is continuing our Phase 3 clinical trials of MDMA-assisted psychotherapy for PTSD at 14 sites in the U.S., Canada, and Israel. The Phase 3 trials are expected to be complete in 2022, meaning that the FDA could approve the treatment as soon as 2023. MAPS is also in the process of obtaining regulatory approvals for Phase 2 trials in the UK, Germany, Czech Republic, and the Netherlands.
PTSD affects millions—and soon to be millions more—due to the global trauma of the COVID-19 pandemic. This includes victims of the disease and their families, health care and emergency service professionals, as well as front-line workers who are risking their lives to provide essential services.
As a non-profit organization focused on mental health services, MAPS is committed to protecting the safety of its study staff and clinical trial participants. MAPS is taking active measures to minimize the risk of exposure to the COVID-19 virus and adhere to physical distancing. As a result of this initiative, new enrollment of participants in MAPS-sponsored trials is temporarily postponed, with treatments continuing for some participants as evaluated on a case-by-case basis.
“I believe this medication-assisted treatment will be a breakthrough in treating trauma,” says Amy Emerson, Chief Executive Officer (CEO) of MAPS Public Benefit Corporation (MAPS PBC). “I would like to thank the investigators leading the studies, study participants for their time and participation, the independent Data Review Committee for their careful analysis, and the amazing research team at MAPS PBC who helped us achieve this milestone in non-profit pharmaceutical development.”
MDMA-Assisted Therapy May Have Lasting Benefits for PTSD, Results Published in Psychopharmacology
On June 10, 2020, MAPS announced the publication of the long-term follow-up results of six Phase 2 clinical trials of MDMA-assisted psychotherapy for the treatment of posttraumatic stress disorder (PTSD) in the peer-reviewed journal Psychopharmacology. The paper is the most comprehensive analysis yet published of the safety and durability of treatment outcomes following MDMA-assisted psychotherapy for PTSD.
The results show that for a majority of participants, the benefits of MDMA-assisted psychotherapy for PTSD extended at least 12 months after the treatment sessions. Sponsored by MAPS, the controlled, randomized, double-blind trials found that, two months following their last session, 56% of 100 participants no longer met diagnostic criteria for PTSD. In the newly published analysis, 91 participants were interviewed at least 12 months later. Of these participants, 67% did not qualify for a PTSD diagnosis. One of the studies included data from an average of 3.8 years after treatment.
“Trauma exposure has emerged as one of the most pressing public health issues of our time and is now at the forefront of global consciousness due to the COVID-19 pandemic and rising visibility of systemic oppression,” said Berra Yazar-Klosinski, Ph.D., paper co-author and Deputy Director and Head of Research Development and Regulatory Affairs at MAPS.
“Although our Phase 3 trials are not yet completed, these long-term data support the hypothesis that MDMA-assisted psychotherapy may provide significant advantages in treatment outcomes, safety, and durability over available PTSD treatments. This is the breakthrough that the world needs right now.”
The trials were conducted by independent investigators in South Carolina (two trials), Colorado, Canada, Switzerland, and Israel. Trial participants included women and men with chronic, treatment-resistant PTSD from a wide variety of causes.
PTSD symptoms were assessed using the Clinician-Administered PTSD Scale (CAPS-IV) at baseline, one to two months after their last MDMA-assisted psychotherapy session, and at least 12 months after their final session. The course of double-blind treatmen
t included one to three eight-hour MDMA-assisted psychotherapy sessions spaced three to five weeks apart, combined with weekly non-drug psychotherapy sessions. Outcomes were assessed by blinded Independent Raters.
Based on these results, in August 2017, the FDA granted Breakthrough Therapy Designation to MDMA-assisted psychotherapy for PTSD, acknowledging that it “may demonstrate substantial improvement over existing therapies” and agreeing to expedite its development and review. The FDA also considered MAPS’ prior published Phase 2 results when it agreed to MAPS’ expanded access program in January 2020. The research also received major confirmation when it passed its crucial interim analysis in May 2020.
The follow-up study found that long-term adverse events were minimal although the benefits were sustained. The most common harm reported at the long-term follow-up was worsened mood, reported by less than 4% of study participants. Further assessment of the long-term benefits and risks of MDMA-assisted psychotherapy is needed in future trials that include control groups.
The Psychopharmacology article was authored by Lisa Jerome, Ph.D., Allison Feduccia, Ph.D., Julie B. Wang, M.P.H., Ph.D., Scott Hamilton, Ph.D., Berra Yazar-Klosinski, Ph.D., Amy Emerson, B.A., Michael C. Mithoefer, M.D., and Rick Doblin, Ph.D.
“These long-term follow-up findings show that once people with PTSD learn that they can productively process traumatic memories instead of suppressing them, they can continue to heal themselves even after they have stopped receiving MDMA-assisted psychotherapy,” said co-author Rick Doblin, Ph.D., MAPS Founder and Executive Director.
MAPS is also in the process of obtaining regulatory approvals for Phase 2 trials in the Czech Republic, Netherlands, Germany, United Kingdom, Portugal, Norway, and Finland.
PTSD is a chronic mental health condition affecting 3-4% of the global population. PTSD can be caused by sexual assault, violent crime, military or law enforcement service, serious illness, and a wide variety of other causes. A new approach to treating PTSD is urgently needed, especially for those who do not respond to existing treatments.
MDMA-assisted psychotherapy uses MDMA to improve the effectiveness of psychotherapy for PTSD. The treatment involves up to three administrations of MDMA (75-125 mg) in conjunction with psychotherapy in a controlled clinical setting as part of a course of psychotherapy. Once approved, patients will not be able to take the MDMA home—patients won’t be filling their prescriptions at their local pharmacy. Instead, MDMA-assisted psychotherapy treatment will only be available through a doctor and only in supervised therapeutic settings from certified clinicians.
FDA Agrees to Expanded Access Program for MDMA-Assisted Therapy for PTSD
On December 20, 2019, the FDA agreed to MAPS’ application for an expanded access program for MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD).
The purpose of the expanded access program is to allow early access to potentially beneficial investigational therapies for people facing a serious or life-threatening condition for whom currently available treatments have not worked, and who are unable to participate in Phase 3 clinical trials.
“We commend FDA for recognizing the great unmet medical need of PTSD by allowing access to MDMA-assisted psychotherapy on a compassionate basis for people with treatment-resistant PTSD,” said MAPS Founder and Executive Director Rick Doblin, Ph.D. “We are delighted to begin generating real-world evidence about this potential new treatment.”
The expanded access protocol will allow 50 patients to receive MDMA-assisted psychotherapy, following the MAPS treatment protocol (maps.org/treatmentmanual). MAPS hopes to expand the number of patients eligible to receive treatment in the expanded access program. MAPS has proposed to the FDA that after the first 35 patients, it will submit patient data for the agency to consider whether to expand the program.
The expanded access protocol differs from MAPS’ ongoing Phase 3 clinical trials in that it is limited to treatment-resistant patients with moderate to severe treatment-resistant PTSD. Other differences are that the FDA is requiring at least one therapist of each therapy pair to have a medical or clinical doctorate degree (M.D., Ph.D., or equivalent), there is no control group, and patients are responsible for the costs of their own treatment.
Up to 10 qualifying treatment sites will be selected to begin the expanded access program, to be announced in the next few months. Over 120 site applications have been received to date. Once the program begins, patients can apply to the individual expanded access sites.
“The resurgence of research into using drugs such as MDMA to catalyze psychotherapy is the most promising and exciting development I’ve seen in my psychiatric career,” said Michael Mithoefer, M.D., Acting Medical Director for MAPS PBC. “Combining the powerful effects of pharmacology with the potential depth of psychotherapy is a compelling model for harnessing advances in neuroscience and psychopharmacology without ignoring the complexity, richness and innate capacity of the human psyche. I’m delighted that the expanded access program will now allow some patients to access to this modality as MAPS’ Phase 3 research continues.
MAPS’ expanded access protocol must still be approved by the U.S. Drug Enforcement Administration (DEA) and the Institutional Review Board (IRB). Based on the FDA’s review as well as the DEA and IRB’s existing support of MDMA-assisted psychotherapy clinical trials, MAPS does not anticipate delays in those approvals.
This is the second time that a government agency has allowed such a program for MDMA-assisted psychotherapy. On February 3, 2019, the Israeli Ministry of Health announced the approval of compassionate use for MDMA-assisted psychotherapy for PTSD, which will also allow 50 patients to receive the treatment. Patients with PTSD will be eligible to receive treatment at four sites throughout Israel.
In August 2017, the FDA granted Breakthrough Therapy Designation to MDMA-assisted psychotherapy for PTSD.
Phase 3 Trials of MDMA-Assisted Therapy for PTSD
While our studies are impacted due to COVID-19, we are continuing to accept applications and begin the screening process for research participants for the MAPS-sponsored Phase 3 clinical trial of MDMA-assisted psychotherapy for PTSD. Participants will help contribute to scientific knowledge and will help us better understand if MDMA-assisted psychotherapy works for the treatment of PTSD. MAPS conducts clinical trials under the guidance and regulations of the FDA, in collaboration with all federal regulators, including the DEA.
The Phase 3 clinical trials are assessing the efficacy and safety of MDMA-assisted psychotherapy in adult participants with moderate to severe PTSD. Over a 12-week treatment period, participants will be randomized to receive 12 non-drug preparatory and integration sessions lasting 90 minutes each, along with three day-long sessions about a month apart of either MDMA or placebo in conjunction with psychotherapy. The primary endpoint will be the Clinician-Administered PTSD Scale (CAPS-5), as assessed by a blinded pool of independent raters.
Our FDA-regulated Phase 3 clinical trials of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) are taking place at 14 locations across the United States, Canada, and Israel. The current Phase 3 trial is being conducted at the following study sites:
- Los Angeles, CA | private practice
- San Francisco, CA | research institution
- San Francisco, CA | private practi
ce - Boulder, CO | private practice
- Fort Collins, CO | private practice
- New Orleans, LA | private practice
- New York, NY | research institution
- New York, NY | private practice
- Charleston, SC | private practice
- Madison, WI | research institution
- Boston, MA | private practice
- Vancouver, Canada | research institution
- Be’er Ya’akov, Israel | research institution
- Tel HaShomer, Israel | research institution
The trials are the final phase of research required by the FDA before deciding whether to approve MDMA as a legal prescription treatment for PTSD. If approved, MDMA will be required to be used in conjunction with psychotherapy in an outpatient setting.
We are currently seeking research participants for Phase 3 clinical trials of MDMA-assisted psychotherapy for PTSD. Participants will help contribute to scientific knowledge and will help us better understand if MDMA-assisted psychotherapy works for the treatment of PTSD. MAPS conducts clinical trials under the guidance and regulations of the FDA in collaboration with all federal regulators, including the DEA. To learn more about our clinical trials or apply to be a study participant, visit this website: mdmaptsd.org
There is now a clear path ahead to make MDMA a legal medicine for millions of people suffering from PTSD. Help heal trauma: maps.org/donate
Israel Embraces Research on MDMA-Assisted Therapy for PTSD
- First two Israeli participants complete treatment in Phase 3 clinical trial of MDMA-assisted psychotherapy for PTSD
- Israel is first national government to approve a compassionate use program for MDMA-assisted psychotherapy
- Israeli Ministry of Health represents the first national government to support therapeutic MDMA research ($500,000 in services)
- MAPS has raised $500,000 through individual donors and the Charles and Lynn Schusterman Family Foundation, and still seeks the final $200,000
On February 26, 2020, MAPS announced that the first two participants have completed treatment in MAPS’ Phase 3 clinical trial of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) in Israel.
The Phase 3 studies, taking place at two sites in Israel, are part of the international series of Phase 3 clinical trials sponsored by MAPS, intended to make MDMA-assisted psychotherapy a legal prescription treatment for PTSD under FDA guidelines.
“Preliminary research has shown that MDMA-assisted psychotherapy may be a profound way to help those who suffer greatly from traumatic experiences such as war or sexual assault,” said Dr. Keren Tzarfaty, Clinical Investigator, Training Supervisor, and Director of Israeli Projects and Collaborations with MAPS. “In the face of the perpetual violence in Israel and the surrounding region, this innovative heart-based treatment can transform suffering to wholeness.”
Over 10% of the Israeli population experiences PTSD, and this figure increases significantly in regions frequented by rocket attacks. Military service is compulsory, and most families in Israel have histories of trauma and persecution.
On February 3, 2019, Israel became the first government to approve a compassionate use program for MDMA-assisted psychotherapy for PTSD, which will allow 50 patients to receive the treatment outside of Phase 3 clinical trials. Patients with PTSD will be eligible to receive treatment at sites throughout Israel, including Rambam Medical Center in Haifa and psychiatric hospitals in Be’er Yaakov, Lev Hasharon, Be’er Sheva, and Sheba-Tel Hashomer.
The U.S. FDA followed Israel on December 20, 2019, when the agency agreed to an expanded access program for MDMA-assisted psychotherapy for PTSD, also for 50 patients with PTSD.
“The Israeli Ministry of Health is constantly looking for new tools to get better results in psychological and psychiatric treatment,” says Bella Ben-Gershon, Director of Psychological Trauma for the Israeli Ministry of Health. “After seeing the very promising results of the completed MDMA-assisted psychotherapy research in Israel, we now believe that it is crucial to allow more citizens who suffer from PTSD to have access to this new treatment.”
Israel is also the first national government to financially support MDMA-assisted psychotherapy research. In February of 2019, the Israeli Ministry of Health granted $500,000 in medical and hospital services to MAPS in support of the compassionate use of MDMA-assisted psychotherapy for PTSD in Israel.
The Israeli Ministry of Health inspired the Charles and Lynn Schusterman Family Foundation, a major philanthropic organization that funds projects in the Jewish community and Israel, to contribute a generous grant to MAPS for the Israeli compassionate use program.
“A society is only as strong as how it cares for its most vulnerable communities,” says Stacy Schusterman, Chair of the Charles and Lynn Schusterman Family Foundation. “I am proud that Israel is leading the world in exploring new ways to support and treat people suffering from PTSD and psychiatric illnesses. The compassionate use program in Israel is an opportunity to help high-risk populations, including IDF soldiers who have served their country, whose mental health needs are often overlooked and underserved.
MAPS estimates the total cost for treating all 50 patients in the Israeli compassionate use program at $1.2 million. With the contributions from the Ministry of Health and the Schusterman Family Foundation, together with additional gifts from Ron Beller, Anat Agmon, Moshe Tov Kreps, and Saggi Malachi, MAPS now has $200,000 left to raise for the Israeli program.
Startle Testing with MDMA: Thirty-First Participant Receives Experimental Treatment
On March 25, 2020, the thirty-first participant completed experimental treatment in our ongoing study of the effect of MDMA on startle testing in healthy participants. Led by Principal Investigator Barbara Rothbaum, Ph.D., this study is conducted at Emory University in Atlanta, Georgia. Enrollment to this study is currently on hold due to COVID-19.
Therapist Training Study: New Protocol Amendment Accepted by the FDA
On May 12, 2020, a new protocol amendment that increases the number of study participants to a total of 120 was accepted by the FDA. This protocol amendment was submitted to the IRB on April 30, 2020. This study is our ongoing Phase 1 study of the psychological effects of MDMA when used in a therapeutic setting by healthy participants. Enrollment in this multi-site study is on hold due to COVID-19 and is limited by invitation only to therapists in training to work on MAPS-sponsored clinical trials of MDMA-assisted psychotherapy for PTSD. The Boulder, Colorado, study site is led by Principal Investigator Marcela Ot’alora G., M.A., L.P.C., the Charleston, South Carolina, is led by Principal Investigator Zhenya Gelfand, M.D., and the Santa Fe, New Mexico, study site is led by Principal Investigator George Greer, M.D.
An Open-Label, Multi-Site Phase 2 Study of the Safety and Feasibility of MDMA-Assisted Therapy for Eating Disorders
MAPS will conduct an open-label, multi-site Phase 2 study for MDMA as an adjunct to psychotherapy for anorexia nervosa restricting subtype (AN-R) and binge-eating disorder (BED). This study will explore the safety and feasibility of MDMA-assisted psychotherapy and adjunctive caregiver involvement in the treatment of individuals with AN-R and BED. The addition of a supportive caregiver as a treatment ally with every participant reflects this most recent development in science and practice. Supportive caregivers enrolled in the study w
ill receive non-drug psychotherapy support. The study will enroll 12 participants who meet the Diagnostic Statistical Manual for Mental Disorders Edition 5 (DSM-5) criteria for AN-R, and 6 participants who meet DSM-5 criteria for BED, for a total of 36 participants (12 AN-R, 6 BED, and 18 caregivers).
The study will take place at three study sites. The study site in Vancouver, Canada, will include six BED participants, with Qualified Investigator Christian Schütz, M.D., Ph.D., M.P.H, overseeing the study. The study sites in Toronto, Canada, and Denver, Colorado, will each include six AN-R participants, with Michael Verbora, M.D., overseeing as Qualified Investigator in Toronto, and co-Clinical Investigators Adele Lafrance, Ph.D., and Mike Rollin, M.D. overseeing the site in Denver.
A Phase 1 Open-Label Study of 3,4-Methylenedioxymethamphetamine (MDMA) Tolerability and Pharmacokinetics in Participants with Moderate Hepatic Impairment Compared to Matched Control Participants with Normal Hepatic Function
MAPS is sponsoring an open-label Phase 1 study of MDMA’s effect on hepatic impairment (liver disease). While the study site is prepared, this study has not yet enrolled any participants and enrollment is on hold due to COVID-19. The primary objective of this study is to evaluate the effect of moderate hepatic impairment on the pharmacokinetics of oral MDMA and its active metabolite 3,4-methylene-dioxyamphetamine (MDMA). The secondary objective of this study is to evaluate the effect of moderate hepatic impairment on the safety and tolerability of oral MDMA. Led by Principal Investigators Janel Long-Boyle, Pharm.D., Ph.D., and Robert M. Grant, M.D., M.P.H., this study will be conducted at the University of California, San Francisco.
MDMA Therapy Training Program Update
Best wishes from the Training and Supervision Department at MAPS PBC! We hope that you, your loved ones, and communities are taking care of your nervous systems and of each other, as current events continue to unfold around the COVID-19 pandemic and the racial justice movement in the United States.
The Center for Psychedelic Psychotherapy and Trauma at the Icahn School of Medicine at Mount Sinai and the Bronx VA sponsored an MDMA-assisted psychotherapy training featuring Michael Mithoefer and Annie Mithoefer for twenty-nine VA clinicians. This Bronx VA training was delivered with the support of MAPS PBC training staff and MAPS investigators. MAPS PBC Trainers Marcela Ot’alora G., L.P.C., and Bruce Poulter, M.P.H., will provide an online nine-day training with Naropa University from September 25-27, October 23-25, and October 30 – November 1. During the month of November, Annie Mithoefer and Michael Mithoefer will be delivering the first-ever international online training to a cohort of therapists in Europe preparing to work on the Phase 2 protocol for the open-label lead-in study for the European segment of Phase 3 clinical trials for MDMA-assisted psychotherapy for PTSD.
The Training Team is excited to learn from our online trainings as we progress with training design and program development. The MDMA Therapy Training Program is carrying out an educational design project to further develop the training pedagogy and competency framework to support the growth and continued quality of the program over the coming years. Additionally, the training program continues to support clinical supervision of active MDMA-assisted psychotherapy studies, as many study sessions are continuing with safety practices in place for COVID-19.
Sign up for the Training Program Newsletter to receive updates on upcoming trainings: mapspublicbenefit.com/therapy-training
Clinical Trials, Safety, and COVID-19
The MAPS-sponsored Phase 3 study of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) has been impacted by the COVID-19 global pandemic. With the guidance of the FDA, MAPS PBC has decided to conclude the study in August 2020 with 90 participants instead of the originally intended 100 participants following discussions with the FDA. MAPS PBC is developing individual plans for participants who began treatment and had study visits delayed due to COVID-19. By August all participants who have been able to continue study visits during COVID-19 lockdown will have completed the study. We greatly appreciate our study participants, and we are committed to ensuring they have an opportunity to complete treatment within the study protocol as soon as possible.
Participate in Research
MAPS sponsors clinical trials around the world that require human participants. Our studies have strict enrollment criteria based on the goal of the study and the condition the study is investigating.
Enrollment for the first of two Phase 3 clinical trials of MDMA-assisted psychotherapy for PTSD has concluded. Our study recruitment website for the second Phase 3 trial of MDMA-assisted psychotherapy for PTSD is accepting applications for select study sites: mdmaptsd.org
We are actively preparing to initiate enrollment for the remaining study sites conducting our second Phase 3 clinical trial of MDMA-assisted psychotherapy for PTSD.
Please visit our Participate in Research page and check it frequently for updates about participant enrollment: maps.org/participate/participate-in-research
