Research News: Spring 2019

MAPS Bulletin Spring 2019: Vol. 29, No. 1

Treating PTSD with MDMA-Assisted Therapy

Phase 3 Trials:
Nine Sites Screening Participants

Our FDA-regulated Phase 3 clinical trials of MDMA-assisted psychotherapy for PTSD are taking place at 15 locations across the United States, Canada, and Israel. Nine study sites are currently recruiting participants.

The Phase 3 clinical trials are assessing the efficacy and safety of MDMA-assisted psychotherapy in adult participants with severe PTSD. Over a 12-week treatment period, participants will be randomized to receive twelve 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.

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.

The Phase 3 trials will be conducted at the following study sites:

In MAPS’ completed Phase 2 trials with 107 participants, 56% no longer qualified for PTSD after treatment with MDMA-assisted psychotherapy, measured two months following treatment. At the 12-month follow-up, 68% no longer had PTSD. Most subjects received just 2–3 sessions of MDMA-assisted psychotherapy. All participants had chronic, treatment-resistant PTSD, and had suffered from PTSD for an average of 17.8 years.

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) if preliminary clinical evidence indicates it may demonstrate substantial improvement over existing therapies.

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.

Israel Approves Compassionate Use of MDMA-Assisted Therapy for PTSD

On February 3, 2019, the Israeli Ministry of Health announced the approval of compassionate use for MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD), which will allow 50 patients to receive the therapy within a treatment protocol. Patients with PTSD will be eligible to receive treatment at four sites throughout Israel, including Rambam Medical Center in Haifa and psychiatric hospitals in Be’er Yaakov, Lev Hasharon, and Be’er Sheva.

“The ministry is taking this seriously and with appropriate caution, an in-depth investigation has been carried out. There is a considerable population in Israel of people suffering from PTSD that is resistant to other treatment,” Bella Ben-Gershon of Israel’s Ministry of Health said to Haaretz News.

Open-Label Lead-In Study of MDMA-Assisted Therapy for PTSD: 31st Participant Completes Treatment

The 31st participant has completed treatment in our Phase 2 open-label lead-in study of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) at planned Phase 3 sites across the United States and Canada. The purpose of this study is to provide the final training and supervision for our co-therapy teams as they each work with one subject with PTSD using the same treatment approach as in Phase 3. All study sites are now fully enrolled. The study is expected to be completed in mid-2019.

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.

Phase 3 trial participant enrollment is open at multiple sites. Please bookmark our Participate in Research page and check it frequently for updates. maps.org/participate/participate-in-research

Therapist Training Study Enrolls 74th Participant

Ongoing study
Location:Charleston, South Carolina, and Boulder, Colorado
Principal Investigator: Zhenya Gelfand, M.D., (Charleston);
Marcela Ot’alora, M.A., L.P.C. and Waul Garas, M.D. (Boulder)
Sub-Investigator:Annie Mithoefer, B.S.N., (Charleston)

On January 15, 2019, the 74th participant officially 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 multi-site study is limited by invitation only to therapists in training to work on MAPSsponsored clinical trials of MDMA-assisted psychotherapy for PTSD. Principal Investigators Marcela Ot’alora, M.A., L.P.C., and Wael Garas, M.D., lead the Boulder, Colorado study site and Zhenya Gelfand, M.D. is serving as Principal Investigator at the site in Charleston, South Carolina with Sub-Investigator Annie Mithoefer, B.S.N.

Cognitive Behavioral Conjoint Therapy for PTSD: Study Close-Out Completed

Completed Study
Location: Charleston, South Carolina
Principal Investigator: Michael Mithoefer, M.D.
Sub-Investigator: Candice Monson, Ph.D.

In July 2018, the study close-out was completed for our study of MDMA combined with Cognitive Behavioral Conjoint Therapy (CBCT) for posttraumatic stress disorder (PTSD) at our Charleston, South Carolina site led by Principal Investigator, Michael Mithoefer, M.D., and Sub-Investigator, Candice Monson, Ph.D. This study enrolled six dyads with one participant diagnosed with PTSD and one concerned significant other who does not have PTSD but does experience psychosocial distress. MDMA was 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.

Startle Testing with MDMA: 12th Pa
rticipant Receives Experimental Treatment

Ongoing study
Location: Emory University in Atlanta,Georgia
Principal Investigator: Barbara Rothbaum, Ph.D.

On February 20, 2019, the 12th participant completed experimental treatment in our ongoing study of the effect of MDMA on startle testing in healthy volunteers. Led by Principal Investigator Barbara Rothbaum, Ph.D., this study is being conducted at Emory University in Atlanta, Georgia. This research group is planning a subsequent study exploring the combination of MDMA with Prolonged Exposure in people with PTSD.

MDMA Therapy Training Program: Expanded Access Update

Training Program
Therapy Training Team: Michael Mithoefer, M.D.,
Annie Mithoefer, B.S.N., Marcela Ot’alora G., M.A., L.P.C.

The MDMA Therapy Training Program has launched a new round of trainings in the U.S., with a special focus on sites interested in offering MDMA-assisted psychotherapy for PTSD in an Expanded Access (compassionate use) protocol. MAPS Public Benefit Corporation (MAPS PBC) submitted the protocol to the FDA in January and is awaiting approval.

Interested and qualified sites may now apply with MAPS PBC to assess eligibility and obtain the required training to administer MDMA-assisted psychotherapy for PTSD under an approved protocol. The basic requirements of a qualified site are (1) a treatment facility conducive to MDMA-assisted psychotherapy; (2) a therapy team, qualified and able to complete MDMA Therapy Training Program; and (3) a prescribing physician who can obtain a DEA Schedule 1 license for MDMA. Only sites in the U.S. and U.S. territories may participate in a U.S. FDA Expanded Access program.

To support the development of compassionate use internationally, from January 27–February 1, 2019, the MDMA Therapy Training Program delivered an MDMA-assisted psychotherapy for PTSD training to 47 therapists, doctors, and counselors in Israel. The event was hosted by the community of Neve Shalom/Wahat al-Salam, “Oasis of Peace,” an intentional village co-founded by Israelis and Palestinians. The training was led by Annie Mithoefer, B.S.N., and Michael Mithoefer, M.D., and Israeli Phase 3 clinical investigators Keren Tzarfaty, Ph.D., MFT, and Ido Siemion, Ph.D. This training event prepared therapy providers to work on a compassionate use protocol in Israel, with approval by the Israeli Ministry of Health to treat 50 participants.

The first U.S. training primarily for Expanded Access therapists took place from March 4 –10 in Asheville, North Carolina, and was led by the Mithoefers. Notably, most of therapists paid for their own training.

More information on therapy training requirements and application procedures for Expanded Access sites and therapy providers can be found at maps.org/training. Each site must submit one site questionnaire. Additionally, each therapy provider must submit a MDMA Therapy Training Program Application for Therapy Providers. Only applicants affiliated with a qualifying site can be considered for training at this time. MAPS PBC will review applications on an ongoing basis as they are received. Applicants can expect a response 3–6 weeks after submitting a complete application. Interested applicants should be familiar with the Treatment Manual (maps.org/treatmentmanual), which describes the MDMA-assisted psychotherapy modality, before submitting an application.

Throughout this year and the coming years, the MDMA Therapy Training Program will host training retreats at various locations across the U.S. On May 4 –11, 2019, Marcela Ota’lora, M.A., L.P.C., and Bruce Poulter, R.N., will lead a training event outside Fort Collins, Colorado. Additionally, MDMA Therapy Training for Communities of Color, led by Marcela Ot’alora MA, L.P.C., and Monnica Williams, Ph.D., A.B.P.P., with support from additional trainers, will take place August 10–17 in Louisville, Kentucky. Additional training retreats, once scheduled, will be announced via the MDMA Therapy Training Newsletter (maps.org/training).

MDMA-Assisted Therapy for Social Anxiety in Autistic Adults

Results Published in Psychopharmacology

Completed study
Location: Los Angeles, California
Principal Investigator: Charles Grob, M.D. and Alicia Danforth, Ph.D.

On September 8, 2018, the results of the first clinical trial of MDMA-assisted psychotherapy for the treatment of social anxiety were published in the peer-reviewed journal Psychopharmacology. All 12 participants in the small pilot study were adults on the autism spectrum, a population that commonly experiences severe social anxiety. The research was conducted by Charles Grob, M.D., and Alicia Danforth, Ph.D., at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.

The study found reductions in the social anxiety that were significantly greater for participants who received MDMA-assisted psychotherapy than for those who received placebo (psychotherapy without MDMA). On average, participants in the placebo group experienced reductions of 19.3 points on the Liebowitz Social Anxiety Scale (LSAS), compared to 44.1 reductions in the MDMA group. Goals for this study included (1) gathering evidence for the safety and effectiveness of MDMA-assisted therapy for adults with autism and 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

Marin: Study Closeout Completed in June 2018

Completed study
Location: Marin, California
Principal Investigator: Phil Wolfson, M.D.
Co-Therpaist: Julane Andries, LMFT

A close-out visit of MAPS’ Phase 2 clinical trial of MDMA-assisted psychotherapy for anxiety associated with life-threatening illness in Marin, Calif., took place on June 20–21, 2018. Led by Principal Investigator Phil Wolfson, M.D., with Co-Therapist Julane Andries, LMFT, this study gathered 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 included (1) gathering data on the safety and effectiveness of MDMA-assisted psychotherapy for participants 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

76th and Final Participant Completes Treatment

Ongoing study
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)

On February 8, 2019, MAPS-sponsored researchers officially completed the first-ever clinical trial of smoked marijuana (cannabis) as a treatment for PTSD symptoms, with all 76 veterans enrolled and treated. The data from the study are now being analyzed and prepared for publication later this year in a peer-reviewed biomedical journal.

“We are thrill
ed to finally be at the finish line of this nearly 10-year saga trying to get this crucial clinical trial completed,” said Site Principal Investigator Sue Sisley, M.D. “We are immensely grateful to all of the study’s supporters, especially the veteran service organizations who helped us with patient recruitment.”

Ayahuasca Research

Data Collection Survey Continues

Ongoing Study
Principal Investigators: 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 in treatment for PTSD. The data collection is sponsored by MAPS, with Jessica Nielson, Ph.D., as Principal Investigator. 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 in the survey, visit 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)

On May 25 and April 12, 2017, the promising results of MAPS-sponsored observational studies of treating opioid dependence with ibogaine-assisted therapy were published in the peer-reviewed American Journal of Drug and Alcohol Abuse. Download both articles for free at maps.org/ibogaine.