MAPS Bulletin Winter 2017: Vol. 27, No. 3
Treating PTSD with MDMA-Assisted Therapy
Phase 3 Trials: FDA Grants Breakthrough Therapy Designation for MDMA-Assisted Therapy for PTSD, Agrees on Special Protocol Assessment
In MAPS’ completed Phase 2 trials with 107 participants, 61% no longer qualified for posttraumatic stress disorder (PTSD) after three sessions of MDMA-assisted psychotherapy two months following treatment. At the 12-month follow-up, 68% no longer had PTSD. All Phase 2 participants had chronic, treatment-resistant PTSD, and had suffered from PTSD for an average of 17.8 years.
On November 29, 2016, the U.S. Food and Drug Administration (FDA) hosted staff and researchers from MAPS and the MAPS Public Benefit Corporation (MPBC) for a formal End of Phase 2 Meeting to discuss clinical trials of MDMA-assisted psychotherapy for PTSD. During the 90-minute meeting at the FDA’s White Oak Campus in Silver Spring, Maryland, the FDA stated they are ready for MAPS to move forward with Phase 3 clinical trials of MDMA-assisted psychotherapy for PTSD.
On July 28, 2017, MAPS and the FDA reached agreement on the Special Protocol Assessment for Phase 3 clinical trials. This agreement confirms that that the protocol design, clinical endpoints, planned conduct, and statistical analyses for the Phase 3 trial are acceptable to support regulatory approval by the FDA.
On August 16, 2017, the FDA granted Breakthrough Therapy Designation to MDMA for the treatment of PTSD. The FDA grants this designation for treatments that (1) are intended alone or in combination with one or more other drugs to treat a serious or life-threatening disease or condition; and (2) preliminary clinical evidence indicates may demonstrate substantial improvement over existing therapies. Breakthrough Therapy Designation also means that the FDA will work closely with MAPS to provide guidance on the development of MDMA for PTSD to design and conduct the development program as efficiently as possible.
The Phase 3 trials starting early next year will assess the efficacy and safety of MDMA-assisted psychotherapy in participants with PTSD, aged 18 and older, at sites in the U.S., Canada, and Israel. Participants will be randomized to receive three day-long sessions of either MDMA or placebo in conjunction with psychotherapy over a 12-week treatment period, along with 12 associated 90-minute non-drug preparatory and integration sessions. The primary endpoint will be the Clinician Administered PTSD Scale (CAPS-5), as assessed by a blinded pool of independent raters.
Throughout September 2017, MAPS and MPBC clinical staff completed nine study initiation visits for sites selected to conduct Phase 3 lead-in trials of MDMA-assisted psychotherapy for PTSD across the United States and Canada. These study initiation visits serve to train clinical trial sites in study procedures before researchers begin to enroll 1–4 participants per site over the next 6-8 months. Each co-therapist team will work with a single participant at their respective study site.
In Spring 2018, sites will begin enrolling approximately 100-150 participants in the first Phase 3 trial (MAPP1), “A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder.”
MAPS’ Phase 3 trials will be conducted at the following study sites:
- Los Angeles, CA | private practice
- San Francisco, CA | research institution
- San Francisco, CA | private practice
- 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 | research institution
- Montreal, Canada | private practice
- Vancouver, Canada | research institution
- Israel | research institution
MAPS and MPBC staff are excited to reach this milestone toward bringing healing to those diagnosed with PTSD through MDMA-assisted psychotherapy. Donations are currently being sought to reach MAPS’ goal of raising $25–35 million to successfully execute the Phase 3 studies required to gain approval from the FDA and European Medicines Agency (EMA) for MDMA-assisted psychotherapy by 2021. With $15.5 million in hand or in multi-year pledges, there’s still a funding gap we need to close.
There is now a clear path ahead to make MDMA a legal medicine for millions of people suffering from PTSD. Help us heal trauma: maps.org/donate.
Marcela Ot’alora, M.A., L.P.C.
Therapist Training Study Enrolls 38th Participant Ongoing study
Location: Charleston, South Carolina, and Boulder, Colorado
Principal Investigator: Michael Mithoefer, M.D., (Charleston), and Marcela Ot’alora, M.A., L.P.C. (Boulder)
Sub-Investigator: Annie Mithoefer, B.S.N., (Charleston)
Estimated study budget: $429,000
Already raised: $160,000
Needed to complete this study: $269,000
On October 10, 2017, the 38th of 100 participants enrolled in our ongoing Phase 1 study of the psychological effects of MDMA when used in a therapeutic setting by healthy volunteers. Enrollment in this study 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, M.A., L.P.C. Michael Mithoefer, M.D., is serving as Principal Investigator at the site in Charleston, South Carolina, with Sub-Investigator Annie Mithoefer, B.S.N.
MDMA Therapy Training Program:
Group Training Takes Place in Colorado and New York Training Program
Location: Charleston, South Carolina, and Boulder, Colorado
Therapy Training Team: Michael Mithoefer, M.D., Annie Mithoefer, B.S.N., Marcela Ot’alora G., M.A., L.P.C.
From April 1–7, 2017, 42 Phase 3 therapists from the U.S., Canada, and Israel participated in MAPS’ MDMA Therapy Training Program (Part D) at the YMCA of the Rockies, Estes Park, Colorado. MAPS’ Part D training consists of five and a half days of experiential learning in non-directive therapy, working with a co-therapist, bodywork, art, and non-ordinary states of consciousness.
One day at each training consisted of Holotropic Breathwork™. Trainees got to experience non-ordinary states induced by breathing, alternating with the experience of sitting for another person. As is the case with MAPS’ Therapist Training Study, it is important for therapists to understand non-ordinary states of consciousness before treating subjects with MDMA-assisted psychotherapy. Holotropic Breathwork™ provides an accessible avenue for more trainees to gain this kind of hands-on training. Experiential work continued with role plays of situations that take place during MDMA-assisted psychotherapy sessions.
Michael Mithoefer, M.D., and Annie Mithoefer, B.S.N., shared case studies highlighting the non-directive approach as well as some of the unique challenges Phase 3 therapy teams might face, such as transference/countertransference and working with transpersonal experiences. Marcela Ot’alora G., M.A., L.P.C., led a dialogue on team development. MPBC Executive Director Amy Emerson and MPBC Clinical Data Scientist Alli Feduccia, Ph.D., joined the training staff to provide important information about screening, study design, and protocol. MPBC Training Program Coordinator Shannon Clare Carlin oriented trainees on the therapeutic use of music in psychedelic psychotherapy. MAPS Founder Rick Doblin, Ph.D., joined each group for the first several days of the training. Prior to these Part D trainings, 42 trainees gathered in Stony Point, New York, to participate in Part D of the MDMA Therapy Training Program from March 18–23.
The program is a prerequisite for anyone working on a therapy team in a MAPS-sponsored Phase 3 trial. The MAPS Therapy Training Program plans to train approximately 300 therapists before 2021, when we anticipate completing Phase 3 clinical trials investigating MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD.
At this point, the training program is not accepting applications, however you can sign up to receive updates when future training opportunities become available. Learn more by visiting maps.org/therapists.
Cognitive Behavioral Conjoint Therapy for PTSD: Sixth Dyad Receives Experimental Treatment Ongoing study
Location: Charleston, South Carolina
Principal Investigator: Michael Mithoefer, M.D.,
Sub-Investigator: Candice Monson, Ph.D.
Estimated study budget: $235,000
Already raised: $165,000
Needed to complete this study: $70,000
On October 10, 2017, the sixth dyad (pair of participants) received their first experimental treatment in our ongoing study of MDMA combined with Cognitive Behavioral Conjoint Therapy (CBCT) for PTSD at our Charleston, South Carolina site led by Principal Investigator, Michael Mithoefer, M.D., and Sub-Investigator, Candice Monson, Ph.D. The fifth dyad received their their final experimental session on October 12, and the second dyad completed the six-month follow-up interview on September 17. Four dyads have finished receiving experimental treatments, and have moved on to follow-up interviews.
The study enrolls dyads with one participant diagnosed with PTSD and one concerned significant other who does not have PTSD but does experience psychosocial distress. MDMA will be administered to both participants to help facilitate communication and connection between participants and therapists.
The primary goal of this study is to develop a combined method of MDMA with CBCT for PTSD. This is the first MAPS-sponsored MDMA study conducted with VA-affiliated researchers and the first to employ measures developed for the DSM-5. There are several important reasons to include significant others in PTSD treatment, in addition to the data supporting the efficacy of CBCT for PTSD.
Barbara Rothbaum, Ph.D.
Startle Testing with MDMA:
Initiation Visit Completed Ongoing study
Location: Emory University in Atlanta, Georgia
Principal Investigator: Barbara Rothbaum, Ph.D.
Estimated study budget: $220,000
Needed to complete this study: $220,000
On August 2, 2017, researchers gathered at Emory University in Atlanta, Georgia, to conduct the official initiation visit for our upcoming Phase 1 study on the effect of MDMA on startle testing in healthy volunteers, led by Principal Investigator Barbara Rothbaum, Ph.D. The study protocol has been cleared by the FDA and the U.S. Drug Enforcement Administration (DEA), and researchers are screening subjects in the fall. This study will be followed by another study exploring the combination of MDMA with Prolonged Exposure in PTSD patients.
MDMA-Assisted Therapy for Social Anxiety in Autistic Adults
Social Anxiety Study Officially Completed
Location: Los Angeles, California
Principal Investigators: Charles Grob, M.D., and
Alicia Danforth, Ph.D.
Estimated study budget: $400,000
Already raised: $13,000 + $15,000 raised by partners
Needed to complete funding for this study: $372,000
On July 10, 2017, investigators gathered for the formal closeout of our study of MDMA-assisted therapy for social anxiety in adults on the autism spectrum. All treatment sessions and long-term follow-up interviews for this study have been completed. Led by Principal Investigators Charles Grob, M.D., and Alicia Danforth, Ph.D., this is a collaborative study between MAPS and the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.
Goals for this study include (1) gathering evidence for the safety and effectiveness of MDMA-assisted therapy for autistic adults diagnosed with social anxiety, (2) determining if additional studies in this area are warranted, and (3) initiating a new program of research into a possible beneficial use of MDMA building on collected case accounts.
MDMA-Assisted Therapy for Anxiety Associated with Life-Threatening Illness
Tenth Participant Completes Long-Term Follow-Up Interview Ongoing study
Location: Marin, California
Principal Investigator: Phil Wolfson, M.D.
Co-Therpaist: Julane Andries, L.M.F.T.
Estimated study budget: $627,000
Already raised: $258,000
Needed to complete this study: $369,000
On August 29, 2017, the 10th of 18 participants completed their 12-month follow-up interview in our ongoing Marin, Calif., study of MDMA-assisted psychotherapy for anxiety associated with life-threatening illness. Led by Principal Investigator Phil Wolfson, M.D., with Co-Therapist Julane Andries, L.M.F.T., this study is gathering preliminary data about the safety and efficacy of MDMA-assisted psychotherapy for anxiety associated with a diagnosis of a life-threatening illness.
Goals for this study include (1) gathering data on the safety and effectiveness of MDMA-assisted psychotherapy for subjects with anxiety associated with life-threatening illness; (2) determining if additional studies are warranted; and (3) initiating MDMA-assisted psychotherapy research for a new clinical indication.
Medical Marijuana Research
28th Participant Enrolls in Smoked Marijuana Trial for Chronic PTSD in Veterans
Location: Phoenix, Ariz.
Coordinating Principal Investigator:
Marcel Bonn-Miller, Ph.D. (University of Pennsylvania)
Co-Investigator/Site Principal Investigator:
Sue Sisley, M.D. (private practice) and
Co-Investigator: Paula Riggs, M.D. (University of Colorado)
Estimated study budget: $2,156,000
Already raised: $2,156,000 grant awarded by the State of Colorado. This study has been fully funded.
On October 11, 2017, the 28th of 76 participants enrolled and received study drug in the first-ever clinical trial of smoked marijuana (cannabis) for PTSD in U.S. veterans. Taking place at the Scottsdale Research Institute (SRI) in Phoenix, Arizona, this clinical trial will evaluate the safety and efficacy of four different potencies of marijuana for symptoms of PTSD.
Data Collection Survey Underway Ongoing study
Principal Investigator: Jessica Nielson, Ph.D.
We are currently collecting responses for the revised version of our anonymous questionnaire about the potential risks and benefits associated with using ayahuasca as a therapy for PTSD. The results of the survey are currently being summarized and prepared for publication, at which point the survey will shift its focus to general ayahuasca use for a variety of conditions, including PTSD, depression and substance abuse/addiction. The data collection is being sponsored by MAPS, with Jessica Nielson, Ph.D., as the Principal Investigator for this study.
Ayahuasca is a psychoactive brew or tea most commonly derived from Banisteriopsis caapi, a vine containing monoamine oxidase inhibitors (MAOIs), and the leaves of Psychotria viridis or other plants containing N,N-dimethyltryptamine (DMT), and often several other admixture plants. Ayahuasca is legal in many countries in South America.
Our revised survey is a shorter and simplified version of the first version, and we welcome participation from anyone that has tried ayahuasca in any context or setting, including those who took the first version of the survey. To participate, take the survey at surveymonkey.com/r/AyaPTSD.
Ibogaine-Assisted Therapy for Drug Addiction
Observational Research Published in American Journal of Drug and Alcohol Abuse Study completed
Locations: Mexico and New Zealand
Principal Investigators: Thomas Kingsley Brown, Ph.D. (Mexico), and Geoff Noller, Ph.D. (New Zealand)
Donations are needed to support ibogaine research.
On May 25 and April 12, 2017, the promising results of MAPS-sponsored observational studies into treating opioid dependence with ibogaine, a naturally occurring psychedelic compound, were published in the peer-reviewed American Journal of Drug and Alcohol Abuse. Sponsored by MAPS in Mexico and New Zealand, both studies show that ibogaine should be further studied as a potential treatment for opioid dependence through rigorously controlled studies.
Ibogaine is a psychoactive compound usually extracted from the West African Tabernanthe iboga plant. In animals, a single dose of ibogaine decreases signs of opioid withdrawal and produces sustained reductions in the self-administration of heroin, morphine, cocaine, nicotine, and alcohol. Ibogaine is illegal in the U.S., and legal but unregulated in Canada and Mexico. New Zealand, South Africa, and Brazil authorize the use of ibogaine by licensed medical practitioners. While its mechanism of action is not yet fully understood, it differs from that of standard opioid agonist treatments such as methadone and buprenorphine which maintain dependence, and thus may show promise as an innovative pharmacotherapy for opioid addiction.
Ultimately, the authors of the studies conclude that given the potential demonstrated by ibogaine’s substantive treatment effect in opioid detoxification, its novel (though not yet fully understood) pharmacological mechanism of action, and its clinical effect in opioid-dependent subjects who have not satisfactorily responded to other treatments, ibogaine has promise for future research and development as a novel pharmacotherapy for opioid addiction.
Download both articles for free at maps.org/ibogaine.