| 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, Rick Doblin founded MAPS as a non-profit
research and educational organization with the mission to act as
a psychedelic and medical marijuana pharmaceutical company. MAPS
immediately opened a Drug Master File for MDMA with data gathered
from the standard preclinical animal toxicity studies required by
FDA . Subsequently, five different applications for permission to
conduct human 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. 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.
MAPS continued to fund animal toxicity studies at Stanford (1986-1988)
and human safety studies at Stanford and Johns Hopkins (1988-1991).
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. A July
24, 1999 teleconference with
the FDA concerning MDMA psychotherapy research to treat anxiety,
depression and pain in cancer patients went very well, with the
FDA indicating a willingness to approve "proof of principle" study.
Unfortunately, Dr. Grob’s other work-related responsibilities made
it difficult for him to find the time to work on the approval process
for this research project.
On March 18, 2000, Rick Doblin and Michael Mithoefer met at an
ayahuasca conference in San Francisco, sponsored by Ralph Metzner,
and begin talking about conducting MDMA psychotherapy research in
the US. This marks the beginning of their effort to study subjects
with chronic posttraumatic stress disorder. On November 9, 2000,
the first subject is treated in Jose Carlos Bouso’s MAPS-sponsored
MDMA/PTSD study in Madrid, Spain. On May 13, 2002, the Spain MDMA/PTSD
study gets shut down due to political pressure, after six subjects
have been enrolled in the study without any persisting adverse effects.
Dr. Grob subsequently decided to focus on the use of psilocybin,
instead of MDMA, in cancer patients, on the accurate theory that
psilocybin research would be less controversial than MDMA research.
In June 2003, MAPS starts formally working with Dr. John Halpern,
McLean Hospital, Harvard Medical School, on the design of a study
administering MDMA-assisted psychotherapy to end-stage cancer patients.
Late in 2003, Dr. Grob managed to obtain approval for his psilocybin/cancer
patient study. |
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