History and Future of the Multidisciplinary Association for Psychedelic Studies (MAPS)

This review (2014) outlines the historic development of the non-profit association MAPS in its mission to develop medical, legal, and cultural contexts for people to benefit from the careful uses of psychedelics and marijuana. These efforts include the development of psychedelics into prescription medicines, training therapists, establishing treatment centers, supporting scientific research into spirituality, creativity, and neuroscience, and educating the public about the risks and benefits of psychedelic substances. They introduced the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) in 1994 and had planned for FDA prescription approval in 2021. Their ongoing efforts include plans for introducing (LSD)-assisted psychotherapies, parallel to harm-reduction strategies, such as the Zendo Project.

Abstract

“This article describes the teenage vision of the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS) that humanity’s future would be aided by the therapeutic and spiritual potential of psychedelic substances. The article traces the trajectory of MAPS from inception in 1986 to its present, noting future goals with respect to research, outreach, and harm reduction. MAPS was created as a non-profit psychedelic pharmaceutical company in response to the 1985 scheduling of 3,4-methylenedioxymethamphetamine (MDMA). Overcoming many hurdles, MAPS developed the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) and plans for FDA prescription approval in 2021. MAPS’ program of research expanded to include a trial of lysergic acid diethylamide (LSD)-assisted psychotherapy for anxiety when facing life-threatening illness, observational studies of ibogaine in the treatment of addiction, and studies of MDMA for social anxiety in people with autism spectrum disorders. MAPS meets the challenges of drug development through a clinical research team led by a former Novartis drug development professional experienced in the conduct, monitoring, and analysis of clinical trials. MAPS’ harm-reduction efforts are intended to avoid backlash and build a post-prohibition world by assisting non-medical users to transform difficult psychedelic experiences into opportunities for growth.”

Authors: Amy Emerson, Linnae Ponté, Lisa Jerome & Rick Doblin

Summary

FORMATIVE YEARS

Rick Doblin founded the Non-Profit Multidisciplinary Association for Psychedelic Studies (MAPS) in 1986 to renew psychedelic research, which had been halted all over the world. Three historical events profoundly influenced Rick’s choice of life mission.

Rick tried LSD several times at age 18 at New College of Florida, and went to the guidance counselor seeking assistance. The guidance counselor handed him a manuscript copy of Dr. Stanislav Grof’s Realms of the Human Unconscious.

Rick started working towards reviving psychedelic research and mainstreaming psychedelic psychotherapy and spirituality 42 years ago, and now there is a renaissance in psychedelic research with more studies underway around the world than at any time in the last 40-plus years.

THE PRECURSOR NON-PROFIT

Rick Doblin, Debby Harlow, and Alise Agar revived the non-profit organization, the Earth Metabolic Design Lab (EMDL), in response to the DEA’s move to criminalize MDMA. EMDL brought together key people in psychiatry and religion and public policy to help prepare a lawsuit.

DEA filed to criminalize all uses of MDMA, but an ALJ recommended it be placed in Schedule 3, leaving its therapeutic use legal while criminalizing its recreational use. DEA then sued EMDL, which won, and MDMA was criminalized.

Rick realized that the only way to legalize the therapeutic use of MDMA was to work through the FDA drug development process, but due to the controversy surrounding MDMA, funding for research into its therapeutic potential was not likely to occur.

MDMA AND MAPS

MDMA was synthesized in 1912, was briefly researched by the U.S. government in the 1950s, and was rediscovered by the psychedelic therapy community in the middle 1970s. It was used in the treatment of neuroses, relationship problems, and PTSD.

Rick wanted to develop psychedelics as prescription drugs through FDA-approved studies, but needed to remain independent of investors and political limitations.

MAPS was formed with the mission to develop medical, legal, and cultural contexts for people to benefit from the careful uses of psychedelics and marijuana.

MDMA was selected as the initial drug target because it offered patients a unique experience of self-acceptance and an enhanced ability to feel and integrate complex, challenging emotions. It was also chosen because the nations of the world were beginning to fund basic research into the risks of MDMA.

Rick formed a non-profit, MAPS, and immediately opened a Drug Master File (DMF). A kilogram of pure MDMA was produced by Purdue chemist Dave Nichols, Ph.D., for $4000.

Five different applications for permission to conduct human research with MDMA were submitted to the FDA between 1986 and 1988, but were all rejected. Two applications were submitted by individual physicians, but were also rejected.

The FDA rejected applications to conduct MDMA research based on hypothetical risks of neurotoxicity, but MDMA researchers claimed that the rejection was based on a cultural prejudice against medical research with drugs that were criminalized, and on personal opposition to human research with psychedelics.

In 1986, MAPS funded animal toxicity studies on MDMA at Stanford and human safety studies involving spinal taps at Stanford and Johns Hopkins. In 1992, the FDA approved the first MDMA IND and recommended that a Phase 1 dose-response safety study be conducted first.

In 1994, the FDA sanctioned the first double-blind, placebo-controlled U.S. Phase 1 study of MDMA. The study found that MDMA caused significant increases in heart rate and blood pressure in healthy volunteers.

Dr. Grob submitted a protocol for the study of cancer patients in 1997, and the FDA indicated a willingness to approve a “proof of principle” study of MDMA-assisted psychotherapy. However, his other work-related responsibilities made it difficult for him to work on the approval process.

Rick Doblin and Michael Mithoefer met in 2000 and began talking about conducting MDMA psychotherapy research in the U.S.

In 2000, MDMA was tested on women survivors of sexual assault with treatment-resistant PTSD. The study was halted in 2002 due to political pressure from the Madrid Anti-Drug Authority.

Rick Doblin’s MAPS protocol for MDMA-assisted psychotherapy was approved by the FDA in 2001, but took two years to be approved by the DEA and an Independent Review Board.

MAPS began working with Dr. John Halpern, McLean Hospital, Harvard Medical School, on a study administering MDMA-assisted psychotherapy to end-stage cancer patients in June 2003. The study was closed due to enrollment challenges, but MAPS plans to resume this line of research in the future.

Michael Mithoefer, M.D., conducted the first FDA-approved U.S. Phase 2 randomized double-blind placebo-controlled study of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD in 2004. The study enrolled mostly women survivors of sexual assault or childhood sexual abuse.

A second Phase 2 pilot study was conducted in 2006 with 12 subjects in Switzerland. Results suggest clinically significant improvements in PTSD symptoms with a trend toward statistical significance.

In 2010, Dr. Mithoefer’s study was completed, and results showed that 20 subjects experienced significant improvements in PTSD severity. A long-term follow-up suggested that therapeutic benefits were sustained over an average of 41 months post-treatment.

MAPS had completed two proof of principle pilot studies of MDMA-assisted psychotherapy in subjects with chronic, treatment-resistant PTSD, with no serious adverse events or evidence of harmful effects.

MAPS negotiated several protocol amendments with the FDA and IRB, including increasing the number of MDMA-assisted psychotherapy sessions from two to three, offering placebo subjects the option to enroll in a second phase study with full-dose MDMA after the primary end in point, and using clinical titration.

With the completion of these studies, MAPS had the foundation for the Phase 2 program and a growing clinical department to support the work of conducting studies. During the time since the studies first started, concerns about toxicity decreased, and the therapeutic model was developed to minimize toxicity. This model is in contrast to existing medications, which are administered daily for months, or often indefinitely, for PTSD.

Progress in the Phase 2 program was slow, but in 2010 a study was started in the U.S. focusing on veterans with war-related PTSD. This study was quickly approved by the FDA and IRB, and a third study was under way.

MAPS’ EXPANDING RESEARCH AGENDA

In January 2007, MAPS expanded its research to include LSD-assisted psychotherapy for subjects with end-of-life anxiety secondary to life-threatening illness. The study received approval from the Swiss Ethics Committee, BAG, and SwissMedic, and was submitted to the FDA in September 2008.

This LSD study marked the culmination of the first phase of the psychedelic renaissance, with the FDA approving the Swiss LSD protocol in 2008. The study was completed in 2012, and the results were submitted for publication in a peer-reviewed scientific journal.

MAPS became interested in supporting observational studies of ibogaine as a treatment for drug addiction in Canada and Mexico. The study was completed with clinics in Mexico where 30 subjects were enrolled, and the results highlight the need for follow-up after treatment.

In 2012, additional progress was made on the MDMA/PTSD Phase 2 program when a study in Israel under Moshe Kotler, M.D., and a study in Boulder under Marcela Otalora, M.A., L.P.C. were started. In 2013, all studies MAPS anticipated requiring were underway.

MAPS expanded its research of MDMA into a new area, a Phase 2 study of MDMA as a treatment for social anxiety in adults on the autism spectrum. The study will test the safety and feasibility of MDMA-assisted therapy to treat social anxiety.

MAPS is a non-profit pharmaceutical company that is actively developing and funding clinical trials with human subjects in accordance with guidelines set forth by the U.S. FDA, the European Medicines Agency, and the International Council on Harmonization (ICH/GCP).

Amy Emerson was hired in 2009 to guide MAPS’ expanding clinical research program. She has implemented SOPs, compliant databases, site and employee training programs, and monitoring processes, and has grown the team to include two part-time medical monitors, an experienced lead Clinical Research Associate, and contract CRAs.

MAPS is able to plan independent multi-center international studies without the concern of maximizing profits or being confined to a university setting. We also have a standardized treatment manual and training program for the therapists.

During Phase 2 studies, MAPS is training therapists to administer psychedelic drugs in therapeutic settings. A Phase 1 placebo-controlled, double-blind, randomized cross-over study was submitted to the FDA and is now underway.

Today, we have a solid drug development infrastructure to take us through Phase 2 and 3 clinical trials of MDMA for PTSD, and to research additional disease indications and drugs. We have 11 FDA-approved protocols across three clinical programs.

Much work is needed to complete the work on the MDMA/PTSD program, including Phase 2 trials, Phase 3 planning, and training of Phase 3 investigators.

We anticipate completing our Phase 2 studies in late 2015 and will apply to the FDA for four programs to help accelerate the development of MDMA for the treatment of chronic treatment-resistant PTSD. The accelerated development programs were put in place to ensure that therapies for serious conditions are approved as soon as possible. If MAPS is able to obtain designation in one or more of these programs, it could shorten the overall time to approval.

MAPS will conduct two Phase 3 studies with 200 subjects per study across multiple sites, and will request FDA permission to conduct Expanded Access (Compassionate Use) studies with cost recovery.

To meet the needs of the Phase 3 program, 300 therapists will need to be trained. After completing the training, some therapists will be able to enroll in MT1, our Phase 1 MDMA safety study.

If MDMA proves safe and efficacious in two Phase 3 studies, it could be approved as a prescription medicine by the FDA and/or the European Medicines Agency in 2021.

PSYCHEDELIC HARM REDUCTION

Millions of individuals use psychedelics outside of supervised medical contexts every year, many of them for the first time. MAPS began offering support at events in 2001, and has helped reduce the number of psychedelic drug-related arrests and hospitalizations.

MAPS’ efforts to provide harm-reduction services first began at Hookahville in Ohio in 2001, followed by the Boom Festival in Portugal in 2002. KosmiCare, a centralized space sponsored by both the festival and the local government, provides compassionate support for anyone having a difficult psychedelic experience.

MAPS released a short film entitled Working with Difficult Psychedelic Experiences that teaches users how to minimize psychological risks and explore the therapeutic applications of psychedelics.

MAPS’ harm-reduction program, the Zendo Project, began at Burning Man in 2012 and expanded to Envision (Costa Rica), AfrikaBurn (Tankwa Karoo, South Africa), and Bicycle Day (San Francisco).

We returned to Burning Man in 2013 to expand our harm-reduction project by collaborating with the Full Circle Tea House. We shuttled volunteers and guests between the Zendo and Tea House.

MAPS strives to educate the public about the risks and benefits of psychedelics, and to encourage honest and responsible conversations about their use. This helps reduce public fears surrounding psychedelics.