MAPS Bulletin Summer 2016 Vol. 26, No. 2 – Research Edition
Treating PTSD with MDMA-Assisted Therapy
Preparing for Phase 3 Trials
As of July 2016, we are preparing to submit the data from our Phase 2 clinical trials of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) to the U.S. Food and Drug Administration (FDA). Our submission will include data from 136 participants in our Phase 2 trials. Later this year, we’ll meet with FDA ofcials in Washington, D.C., to agree on the design our Phase 3 trials-with 400 or more additional participants- which we anticipate starting in early 2017. As long as we receive the funding needed to complete the research, we anticipate FDA approval of MDMA-assisted psychotherapy as a treatment for PTSD as early as 2021.
Final Subject Completes Long-Term Follow-Up Interview in U.S. Veterans Study (Ongoing Study)
Location: Charleston, South Carolina
Principal Investigator: Michael Mithoefer, M.D., with
co-therapist Annie Mithoefer, B.S.N.
Estimated study budget: $1,429,000
Already raised: $1,429,000
This study has been fully funded.
On July 30, 2016, the 24th and fnal participant completed their 12-month follow-up interview in our largest Phase 2 study of MDMA-assisted psychotherapy for 24 U.S. veterans, frefghters, and police ofcers with chronic, treatment-resistant PTSD. Led by Principal Investigator Michael Mithoefer, M.D., and co-therapist Annie Mithoefer, B.S.N., in Charleston, South Carolina, the data from this study are now being prepared for analysis and publication in a peer-reviewed scientifc journal. “When we applied to the FDA for our frst study in October 2001, primarily aimed at treating people with crime-related trauma such as childhood sexual abuse, rape, or other assault, we didn’t know that the Afghanistan and Iraq wars would be starting soon,” writes Dr. Mithoefer in his article in the Winter 2015 MAPS Bulletin. “Since then, the need for additional treatments for returning veterans with PTSD has become painfully and increasingly pressing.”
Approximately half of the 24 subjects have also enrolled in our ongoing sub-study, in collaboration with researchers at the Medical University of South Carolina (MUSC), of the physiological efects of MDMA-assisted psychotherapy. This sub-study is using heart rate variability (HRV) and functional magnetic resonance imaging (fMRI) to explore correlations with clinical outcomes.
Goals for this study include (1) gathering evidence for the safety and efectiveness of MDMA-assisted psychotherapy in people sufering from war-related trauma; (2) comparing the effectiveness of the treatment for people with war-related trauma versus for people with trauma related to sexual abuse, assault, and other causes; (2) comparing diferent doses of MDMA for therapeutic efectiveness and ability to create a successful double-blind; and (3) increasing awareness and support for our work by assisting a population with mainstream public recognition.
17th Participant Completes Long-Term Follow-Up Interview in Boulder Study (Ongoing Study)
Location: Boulder, Colorado
Principal Investigator: Marcela Ot’alora, M.A., L.P.C.
Estimated study budget: $771,000
Already raised: $771,000
This study has been fully funded.
On July 6, 2016, the 17th participant completed their 12-month long-term follow-up interview in our Phase 2 study of MDMA-assisted psychotherapy for subjects with chronic, treatment-resistant PTSD in Boulder, Colorado. 23 subjects will be included in our fnal analysis, while all 29 subjects, including six who dropped out or were excluded for not meeting study criteria, will be included in our intent-to-treat analysis. All subjects have now completed active study participation. Long-term follow-up data will provide additional information to guide the design of our upcoming Phase 3 trials. The fnal study results were prepared for publication in the frst half of 2016, with publication expected later in 2016. In addition to obtaining Phase 2 data on the safety and efectiveness of MDMA-assisted psychotherapy for PTSD, this study is also comparing outcomes between diferent combinations of male/female co-therapist teams. Study participant Hania Withem presented a brief address at MAPS’ 30th Anniversary Banquet and Celebration on April 17, 2016, at the Scottish Rite Center in Oakland, Calif. (read her story on page 8).
Goals for this study include (1) gathering evidence for the safety and effectiveness of MDMA-assisted psychotherapy for subjects with PTSD from a variety of causes, (2) comparing different doses of MDMA for therapeutic efectiveness and ability to create a successful double-blind, (3) exploring whether using intern co-therapists can reduce costs while maintaining treatment efectiveness, and (4) training the next generation of psychedelic psychotherapists.
Final Experimental Treatment Completed in Israeli Study (Ongoing Study)
Location: Beer Yaakov, Israel
Clinical Investigator: Moshe Kotler, M.D.
Estimated study budget: $509,000
Already raised: $509,000
This study has been fully funded.
On March 24, 2016, the fnal open label experimental treatment session was completed in our Israeli Phase 2 study of MDMA-assisted psychotherapy for PTSD. In addition to being the final experimental session in this study, it was also the fnal experimental session in Phase 2 of MAPS’ plan to develop MDMA-assisted psychotherapy into a legal treatment for PTSD. Led by Principal Investigator Moshe Kotler, M.D., this Phase 2 study has treated 10 subjects with chronic, treatment-resistant PTSD from any cause. “We are in the fnal stages of the Phase 2 research in Israel, having worked over the last few years with a variety of participants, their stories, feelings, body experiences, and the traumas that these refect,” reports co-therapist Keren Tzarfaty, Ph.D. “As these intense processes unfold and old layers melt, we have been witnessing new seeds of healing and growth, love and hope, seeds of wholeness.” Once the fnal evaluations are complete, we will gather data for inclusion in an international meta-analysis of the safety and efficacy of MDMAassisted psychotherapy for the treatment of PTSD.
Goals for this study include (1) gathering evidence for the safety and efectiveness of MDMA-assisted psychotherapy for subjects with PTSD mostly related to war and terrorism, (2) comparing diferent doses of MDMA for therapeutic efectiveness and ability to create a successful double-blind, (3) working in direct association with the Israeli Ministry of Health, and (4) exploring the use of MDMA-assisted psychotherapy in other cultural contexts.
Enrollment Concluded in Canadian Study (Ongoing Study)
Location: Vancouver, British Columbia, Canada
Principal Investigators: Ingrid Pacey, M.D.
Estimated study budget: $470,000
Already raised: $46,000 + $69,000 raised by partners
Needed to complete this study: $355,000
On November 2, 2015, enrollment was concluded in our study of MDMA-assisted psychotherapy for PTSD from sexual assault, violent crime, military service, or any other cause, taking place in Vancouver,
Canada. The final results are being prepared for inclusion in our End-of-Phase 2 submission to the U.S. FDA. Led by Principal Investigator Ingrid Pacey, M.D., in Vancouver, B.C., this small pilot study gave Canadian therapists experience with a MAPS-sponsored Phase 2 clinical trial of MDMA-assisted psychotherapy for PTSD, with data collected from three women and three men. All participants have completed treatments and are in long-term follow-up.
Goals for this study include (1) gathering evidence for the safety and efectiveness of MDMA-assisted psychotherapy for subjects with PTSD from a highly skilled co-therapist team, (2) comparing diferent doses of MDMA for therapeutic efectiveness and ability to create a successful double-blind, and (3) initiating the frst Canadian research into the potential benefts of psychedelic psychotherapy in over 40 years.
13th Participant Enrolled in Therapist Training Study (Ongoing Study)
Location: Charleston, South Carolina
Principal Investigator: Michael Mithoefer, M.D.
Estimated study budget: $429,000
Already raised: $35,000
Needed to complete this study: $394,000
On July 5, 2016, the 13th participant was enrolled in our ongoing Phase 1 study of the psychological efects of MDMA when taken in a therapeutic setting by healthy volunteers. Enrollment in this study is limited to therapists in training to work on MAPS-sponsored clinical trials of MDMA-assisted psychotherapy for PTSD, with enrollment by invitation only. The Principal Investigator of this study is Michael Mithoefer, M.D. On May 9, in preparation for expanding our MDMA-assisted psychotherapy for PTSD development program into Phase 3, we submitted an amendment to the study protocol to the FDA. The amendment included increasing total enrollment to 100 participants and adding a second site in Boulder, Colorado, under the direction of Marcela Ot’alora, M.A., L.P.C., in order to increase enrollment to cover training needs over the next fve years. The FDA gave clearance for the third protocol amendment on June 21, 2016. “We felt quite strongly that we should go through the therapist’s training,” says study participant Dr. Mathew Hoskins in a recent interview with Inverse. “We’re asking our participants in our study to do really quite a lot.”
Are you interested in learning more about being a Phase 3 MDMA-assisted psychotherapy for PTSD researcher? Contact us at askMAPS@maps.org.
Therapist Training Program: Group Training Takes Place in Colorado (Training Program)
Location: Charleston, South Carolina
Principal Investigators: Michael Mithoefer, M.D., with co-therapist Annie Mithoefer, B.S.N.
From April 24-May 1, 2016, 19 therapists participated in a one-week training in the techniques of MDMA-assisted psychotherapy for PTSD in Fort Collins, Colorado. Led by MAPS-sponsored researchers Michael Mithoefer, M.D., Annie Mithoefer, B.S.N., and Marcela Ot’alora, M.A., L.P.C. trainees learned the modality of MDMA-assisted psychotherapy as outlined in the Treatment Manual, watched videos of therapy sessions from Phase 2 trials, and dialogued with therapists in training about the therapeutic approach. MAPS’ four-part training program includes two in-person trainings, and is required for co-therapists who will be working on MAPS’ Phase 3 trials of MDMA-assisted psychotherapy PTSD, which are planned to start in 2017. In-person trainings will be provided in September 2016, October 2016, and January 2017 to accommodate the cotherapists preparing for Phase 3 trials.
On May 25, 2016, MAPS issued the 8th edition of our Treatment Manual for MDMA-Assisted Therapy in the Treatment of PTSD. The Treatment Manual provides researchers with a standardized method of MDMA-assisted psychotherapy to be used as a model in conducting manualized clinical trials. This manual is intended only for use with subjects of an approved clinical trial who have provided their informed consent.
The MAPS Therapist 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.
Conjoint Therapy: DEA, FDA, and IRB Approve Study Protocol (Study in development)
Location: Charleston, South Carolina
Principal Investigator: Michael Mithoefer, M.D.
Sub Investigator: Candice Monson, Ph.D. Estimated study budget: $200,000
Already raised: $165,000
Needed to complete this study: $35,000
On June 14, 2016, the U.S. Drug Enforcement Administration (DEA) approved the protocol for our upcoming study of MDMA combined with Cognitive-Behavioral Conjoint Therapy (CBCT) for treating PTSD. On March 16, 2016, the Independent Review Board (IRB) approved the protocol, and the U.S. Food and Drug Administration (FDA) accepted the protocol on January 26, 2016. Taking place in Charleston, South Carolina, and led by Principal Investigator Michael Mithoefer, M.D., and Sub-Investigator Candice Monson, Ph.D., this will be a pilot Phase 1/Phase 2 open-label study exploring Cognitive Behavioral Conjoint Therapy (CBCT) integrated with MDMA-assisted psychotherapy for the treatment of chronic posttraumatic stress disorder (PTSD). Candice Monson, a developer of CBCT, was introduced to MAPS by the U.S Department of Veterans Afairs National Center for PTSD.
The study will enroll 10 pairs of participants, with one participant diagnosed with PTSD and one concerned signifcant other who does not have PTSD but does experience psychosocial distress. This is the frst MAPS-sponsored MDMA study conducted with VA-afliated researchers and the frst to employ measures developed for the DSM-5. There are several important reasons to include signifcant others in PTSD treatment, in addition to the data supporting the efcacy of CBCT for PTSD. 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 explore a combined method of MDMA with CBCT for PTSD. The study has received approval from all necessary government agencies, and will begin screening local participants residing around South Carolina for enrollment this summer.
Over $152,721 Raised for Purchase of GMP MDMA Supply for Phase 3 Trials
On April 17, 2016, MAPS’ 30th Anniversary Banquet and Celebration was held at the Scottish Rite Center in Oakland, Calif, with the goal of raising funds toward the purchase of one kilogram of 3,4-methylenedioxymethamphetamine (MDMA) certified under current Good Manufacturing Practices (GMP). Additional fundraising efforts towards the purchase of GMP MDMA took place during the spring and early summer of 2016, with 82 Global Psychedelic Dinners held in 16 countries. In total, the money raised around the 30th Anniversary and the Dinners was over $152,721.
This supply of GMP MDMA will be used for our upcoming Phase 3 trials of MDMA-assisted psychotherapy for PTSD, which will begin in 2017. The GMP MDMA will not be any purer than our existing supply, but has been created with complete documentation and validation of all manufacturing procedures as required by the FDA and the European Medicines Agency (EMA) for use in Phase 3 trials. The purchase of GMP MDMA will cost $400,000. If you would like to host a Global Psychedelic Dinner to help raise the
remaining funds, visit psychedelicdinners.org, or give now at maps.org/donate.
MDMA-Assisted Therapy for Social Anxiety in Autistic Adults
11th Participant Treated; IRB Approves Two Additional Subjects (Ongoing Study)
Location: Los Angeles, California
Principal Investigator: Charles Grob, M.D., and Alicia Danforth, Ph.D.
Estimated study budget: $400,000
Already raised: $13,000 raised + $15,000 raised by partners
Needed to complete this study: $372,000
On June 29, 2016, the IRB approved an amended protocol to enroll two additional subjects in our ongoing study of MDMA-assisted therapy for social anxiety in adults on the autism spectrum. On February 27, 2016, the 11th participant received their last blinded experimental session. Sponsored by MAPS, this is a collaborative study between MAPS and the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, with blood plasma biomarker analysis conducted by researchers at Stanford University. “During the actual drugassisted treatment sessions, both structured and unstructured tasks will be employed, including but not limited to listening to preselected music, working with art supplies, writing in journals, silent introspection, and engaging in rapport building interactions with therapists,” write the researchers in the March 2015 article published in Progress in Neuro-Psychopharmacology & Biological Psychiatry. “In addition, subjects will complete the TASIT, which is an interactive, video-based assessment of social inference skills. The co-therapists, always one male and one female to manage potential transference during therapy, will emphasize creating and communicating a setting of safety and support for the subject during periods of inner focus.”
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 Treated in Marin Study (Ongoing Study)
Location: Marin, California
Principal Investigator: Phil Wolfson, M.D.
Estimated study budget: $627,000
Already raised: $214,000
Needed to complete this study: $414,000
On June 6, 2016, the tenth participant was treated in our ongoing study of MDMA-assisted psychotherapy for anxiety associated with life-threatening illness in Marin, Calif. Led by Principal Investigator Phil Wolfson, M.D., with co-therapist Julane Andries, LMFT, this study is gathering preliminary data about the safety and efcacy of MDMA-assisted psychotherapy for treating anxiety in 18 subjects diagnosed with a life-threatening illness. “I can live my life right now,” explains study participant Wendy Donner. “That is such a gift for me.”
On May 3, MAPS was a proud participant in Silicon Valley Gives, an online fundraising efort led by the Silicon Valley Community Foundation with proceeds supporting this trial. On April 3, investigators announced that the frst participant has been scanned in an additional fMRI brain imaging study of the physiological correlates of MDMA-assisted psychotherapy in subjects with anxiety associated with life-threatening illness. The brain imaging sub-study is a collaboration between the MAPS-sponsored study and Michael Silver, Ph.D., at the Helen Wills Neuroscience Institute at the University of California, Berkeley.
Goals for this study include (1) gathering data on the safety and efectiveness 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
Marijuana for PTSD: Researchers Prepare for First-Ever Trial of Medical Marijuana for PTSD in Veterans (Study in development)
Location: Baltimore, Md., and Phoenix, Ariz.
Coordinating Principal Investigator: Marcel Bonn-Miller, Ph.D. (University of Pennsylvania)
Co-Investigators/Site Principal Investigators: Sue Sisley, M.D. (private practice) and Ryan Vandrey, Ph.D. (Johns Hopkins University)
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
From June 6-16, 2016, a series of investigator meetings and initiation visits took place in preparation for our upcoming study of smoked marijuana for symptoms of PTSD in U.S. veterans. Principal Investigators, study coordinators, and study physicians met in Palo Alto, CA, Baltimore, MD, and Phoenix, AZ, to discuss study procedures, receive training on the electronic platforms to be used in the study, and review protocols for recruitment, enrollment, and study publicity. Discussions at these meetings led to an amendment to the study protocol to clarify several study procedures and adjust study measures. Once the amendment has been approved by the Institutional Review Boards (IRBs) at the Scottsdale Research Institute (Phoenix) and Johns Hopkins University (JHU), we will be able to begin recruiting and enrolling participants. We currently expect that this study, the frst-ever randomized controlled trial of whole plant medical marijuana (cannabis) as a treatment for PTSD in U.S. veterans, will begin in August 2016.
On April 19, 2016, the U.S. Drug Enforcement Administration (DEA) formally approved the study. The DEA’s approval marks the frst time a clinical trial intended to develop smoked botanical marijuana into a legal prescription drug has received full approval from U.S. regulatory agencies, including the DEA, FDA, and IRBs. The randomized, blinded, placebo-controlled study will test the safety and efcacy of botanical marijuana in 76 U.S. military veterans with treatment-resistant PTSD. The study is funded by a $2.156 million grant from the Colorado Department of Public Health and Environment (CDPHE) to MAPS, which is sponsoring the study. MAPS’ study protocol will be replicated using vaporization by the Canadian medical marijuana producer Tilray, and by the University of Sydney using Tilray extracts in orally administered capsules.
The Principal Investigator for this study is Marcel BonnMiller, Ph.D., of the University of Pennsylvania. Paula Riggs, M.D., of the University of Colorado, is serving as an additional Co-Investigator to help ensure the study’s scientifc integrity. The study site in Phoenix, Arizona, will be led by Co-Investigator/Site Principal Investigator (PI) Sue Sisley, M.D. Half of the study’s 76 subjects will be treated at the Phoenix site, with the other half treated at Johns Hopki
ns by Co-Investigator/Site PI Ryan Vandrey, Ph.D.
On February 20, 2016, Sue Sisley, M.D., gave a presentation to commissioners of the American Legion in Washington, D.C., about MAPS’ eforts to initiate our clinical trial of medical marijuana for PTSD in U.S. veterans. The talk, titled “Barriers to Researching Medicinal Marijuana,” was presented to the American Legion’s Veterans Afairs and Rehabilitation Commission, TBI and PTSD Committee, as part of their 2016 conference. “I have heard great feedback from the American Legion commissioners who attended saying they felt that it was incredibly successful,” reports Dr. Sisley. “They did not believe any issue related to marijuana would be so warmly embraced. They kept thanking me for opening their eyes to a very legitimate injustice of science being shackled by politics.”
Ayahuasca Research
Data Collection Survey Underway (Ongoing Study)
Principal Investigator: Jessica Nielson, Ph.D.
A new anonymous questionnaire is gathering preliminary data about the potential risks and benefts associated with taking ayahuasca as a therapy for PTSD. The data collection is being sponsored by MAPS. Jessica Nielson, Ph.D., is the Principal Investigator for this study. To participate, take the survey at surveymonkey.com/r/AyaPTSD.
Ibogaine Treatment for Drug Addiction
Data Prepared for Publication in Scientific Journals
Locations: Mexico and New Zealand
Principal Investigators: Thomas Kingsley Brown, Ph.D. (Mexico) and Geoff Noller, Ph.D. (New Zealand)
All treatments have been completed in our two observational studies of ibogaine-assisted therapy for drug addiction, which took place at independent treatment centers in Mexico and New Zealand. We anticipate that data from both studies will be published in peer-reviewed scientifc journals this year. Both of these studies observed the long-term efects of ibogaine treatment for opioid dependence, and the data from each study will be compared to evaluate how ibogaine treatment varies between diferent centers. Goals for these study included (1) gathering preliminary evidence about the safety and potential benefts of ibogaine-assisted therapy for opiate addiction, (2) comparing the safety and efectiveness of diferent ibogaine treatment centers, and (3) initiating and encouraging psychedelic research in New Zealand.
If you would like to apply to participate in our study of MDMA-Assisted Therapy for Social Anxiety in Autistic Adults, and reside in the Los Angeles area, visit mdma-autism.org/participate.
