MDMA was synthesized in 1912 and patented in Germany by Merck in 1914 but was not the subject of human research at that time. In the 1950s it was briefly researched by the U.S. Government as part of the CIA's and the Army's chemical warfare investigations. It was forgotten until the middle 1970s when it was rediscovered by the psychedelic therapy community and began to be used as an adjunct to psychotherapy by psychiatrists and therapists who were familiar with the field of psychedelic psychotherapy. MAPS published a book, The Secret Chief, about the leader of this therapy community. 

In the early 1980s, the drug began to be used non-medically, particularly in Texas, under the name Ecstasy. Both the non-medical and therapeutic use of MDMA were made illegal in 1985 despite the Drug Enforcement Administration Administrative Law Judge Francis Young's recommendation that physicians be permitted to continue to administer it to their patients. Rick Doblin, Alise Agar and Debby Harlow helped coordinate the pro-MDMA contingent in the DEA lawsuit. For an excellent history of the early use of MDMA, see Pursuit of Ecstasy by Beck and Rosenbaum. 

In 1986, with the goal of developing MDMA's therapeutic potential through FDA-approved protocols, a non-profit organization opened a Drug Master File for MDMA with data gathered from the standard preclinical animal toxicity studies required by FDA. Five different applications for permission to conduct research with MDMA were submitted to FDA between 1986 to 1988, to the Neuropharmacologic Drug Products Division directed by Dr. Paul Leber. All five applications were rejected. Three protocols for double-blind controlled trials were from researchers at, respectively, Harvard Medical School, UC San Francisco Medical School, and U. of New Mexico Medical School, and were all rejected. Two applications submitted by individual physicians were for single case studies, one for a terminal cancer patient who had been successfully treated for pain with MDMA-assisted psychotherapy prior to the criminalization of MDMA and the other for a unipolar depression patient for whom all available treatments had been attempted without success. Both of these single-patient INDs were also rejected. The FDA based its rationale for rejecting all protocols and single case studies on the hypothetical risk of functional consequences of potential neurotoxicity from MDMA Proponents of MDMA research claimed that the rejection of all efforts to conduct FDA-approved MDMA research was based not on rational risk/benefit assessments but on an underlying cultural prejudice against medical research with drugs that were criminalized and on one or more FDA officials' personal opposition to human research with psychedelics. Since FDA Review Divisions are sometimes described as operating like fiefdoms under the control of their Directors, proponents felt profoundly stymied. Proponents claimed that concerns about MDMA neurotoxicity, which numerous studies had failed to link with functional or behavioral consequence and which in any case had not been clearly demonstrated to occur at all at therapeutic does levels, were reminiscent of scientific research in the 1960s that claimed to prove that LSD damaged chromosomes. These reports were effective in generating public disapproval of LSD and in hindering research but were later determined to have no clinically significant effect.

In 1992, FDA reviewed a MAPS-supported protocol submitted by Dr. Charles Grob, then at UC Irvine, for a study of the use of MDMA in the treatment of pain, anxiety and depression in cancer patients. FDA's Drug Abuse Advisory Committee recommended that the cancer patient study be postponed and that a Phase 1 dose-response safety study be conducted first. The protocol was redesigned, with FDA giving final approval for the Phase 1 safety study on November 5, 1992. The safety study was completed in 1995. Data from the safety study revealed no unusual risks and indicated that MDMA could be safely administered within a clinical research context. Dr. Grob submitted the first draft of the protocol for the study of cancer patients in 1997. Negotiations with FDA moved very slowly, due to initial FDA decisions to put MDMA psychotherapy research on a slow track to nowhere. However, FDA opposition eventually lessened as MAPS and Dr. Grob persisted in our efforts to obtain permission for research into the use of MDMA-assisted psychotherapy in cancer patients. 

MAPS and MDMA Research

Doblin founded MAPS in 1986 when it became clear that only through FDA-approved research would MDMA ever become legal again. After years of effort, the first FDA- approved research with MDMA was finally approved in 1992 under the direction of Dr. Charles Grob, Harbor-UCLA. 

MDMA is off-patent and is considered to be an Orphan Drug, meaning that the pharmaceutical industry sees no financial incentives in conducting research with it. As a result of the non-medical use of MDMA, funding from government agencies for studies into the beneficial uses of MDMA have not been obtainable. MAPS has been working to support MDMA research since 1986 and opened a Drug Master File for MDMA at the FDA. Opening a Drug Master File is a required step for any drug before it can be legitimately researched in the U.S. MAPS has spent over $170,000 on MDMA research since 1986 and has supported FDA-required animal toxicity studies at the University of Arkansas and Stanford (1986-1988), human safety studies at Stanford and Johns Hopkins (1988-1991), and Dr. Charles Grob's FDA-approved Phase 1 study into the physiological and psychological effects of MDMA in humans (1992-1995). 
Most recently MAPS granted $6,000 to the Psychiatric University Hospital in Zürich for a PET scan study of MDMA-naive subjects and $10,000 for the publication of papers on EEG and prepulse inhibition in ecstasy users. Since 1986, MAPS' primary research goal has been a therapy study in cancer patients. 

MDMA with Cancer Patients - U.S. Research

The proposed study of MDMA psychotherapy in the treatment of cancer patients (Harbor UCLA Hospital) will be the first investigation of the therapeutic potential of MDMA ever conducted in the U.S. We have assembled an excellent team of scientific advisors including Dr. Lester Grinspoon of Harvard Medical School, Dr. Carl Simonton, the developer of the Simonton method of treating the psychological aspects of cancer, and Dr. Jeanne Achterberg, an advisor on guided imagery to the National Institutes of Health's Office of Alternative Medicine, the senior editor of the Journal of Alternative Therapies, and the past president of the Association for Transpersonal Psychology.

The rationale for the proposed study is based in part on numerous remarkable anecdotal accounts of the therapeutic use of MDMA in the treatment of cancer patients. An excellent description of the effect of MDMA is that it "reduces the fear response to a perceived emotional threat." MDMA promotes feelings of peacefulness and acceptance that enable people to move through denial and defense in order to respond clearly to difficult realities and to experience complex emotions.

Clinical case reports suggest that MDMA can reduce acute and chronic pain experienced by end-stage cancer patients, perhaps that portion of total pain and suffering resulting from emotional, psychological, cognitive, and social variables. In one case reported by Greer, the debilitating pain associated with multiple myeloma was significantly alleviated during an MDMA session in which the patient practiced visualization techniques for pain control. A dramatic reduction in pain persisted for several months following the MDMA session. To date, no scientific studies have been attempted to evaluate the safety, efficacy or mechanism of action of MDMA as an adjunct to the reduction of pain in end-stage cancer patients, as a treatment of anxiety and depression, or as a tool to facilitate psychologically-mediated stimulation of the immune system. 

MDMA Research in other countries

MAPS is currently supporting the efforts of researchers in Switzerland, Israel and Spain. The proposed studies in Spain and Israel are for MDMA psychotherapy in the treatment of post traumatic stress disorder (PTSD). MAPS tried to start MDMA/PTSD research in Nicaragua from 1993 to 1995. When it became clear that research in that country would not be sufficiently rigorous, MAPS abandoned the effort. 

2000: New Challenges

MAPS' work has recently gotten much more difficult. You might expect that this is due to political obstacles restricting opportunities to conduct research into the therapeutic potential of psychedelic drugs and marijuana. MAPS' new difficulties result not from political obstructionism but rather from the success of the efforts to obtain permission to conduct research! Now we have to address the inherent complexity of conducting rigorous scientific research into the specific methods by which MDMA can be used to treat clearly defined and meticulously measured aspects of psychological and physical illness, as well as ways it can be used to promote health. It is relatively easy to stand outside the scientific arena and proclaim that one has a wonder drug useful for this or that purpose, if only the powers that be would permit the necessary research. It is much harder to back up those claims with rigorously gathered scientific data when the doors to the laboratory are finally unlocked. 

Naturally, it is a great relief to face these more difficult challenges after struggling for years and decades simply to obtain scientific freedom. Still, it is somewhat befuddling to be in such a position of opportunity. MAPS has been working since its founding in 1986 to obtain permission to study the therapeutic use of MDMA in cancer patients. On June 24, 1999, a teleconference took place between several FDA officials and Rick Doblin (MAPS president), Dr. Charles Grob (principal investigator for the MDMA/cancer patient study), Loren Miller (a consultant assisting MAPS on protocol design and FDA relations issues-- this is not the same Loren Miller associated with an ayahuasca patent) and Matt Baggott (working for MAPS to review all animal and human studies published in peer review journals on MDMA for summary and submission to FDA). According to the memorandum of that teleconference prepared by FDA, " The Center [FDA's Center for Drug Evaluation and Research, which is in charge of research on all new drugs for humans] has decided to allow the sponsor [MAPS] to undertake a proof of principle study..." 

Now we are faced with the exceedingly difficult question of how to measure exactly what MDMA can do to help cancer patients face their illness and impending death. Are we going to show change on standard measures of anxiety and depression, even though these tests have not been created to evaluate people facing death? How do we respond to the fact that the most appropriate measure of Quality of Life in terminal patients, the measure that explicitly evaluates a transcendent dimension related to changes in fear about and acceptance of death, is not yet scientifically validated for use in clinical research? Fortunately, the FDA is willing to let us start with a small pilot study with controls to determine what changes we are able to produce in a variety of measures.