List of Speakers
Talk by George Greer, MD
Talk by Drs. Juraj and Sonja
Talk by Mark A. Kleiman,
Video clips of some of the talks
View pictures that go with this article
Clinical Research with MDMA and MDE
A MAPS' Conference: Dead Sea, Israel
It has taken me some time to reflect on the enduring accomplishments of MAPS'
international scientific conference on clinical research with MDMA and MDE. The
conference took place August 30-September 1, 1999 at the Dead Sea, Israel. Attending the
conference were representatives of every team in the world that has administered MDMA
or MDE to human subjects, along with three teams (from Israel, Spain and the US)
proposing to initiate MAPS-sponsored MDMA psychotherapy research (for a list of
Vol. IX No. 3, p. 9). In addition to the
conference, MAPS organized a six-day pre-conference tour of Israel for 33 people, paid for
by tour participants. I'll first discuss the accomplishments of the conference and pre-
conference tour, then report on some of the new data that was presented about MDMA,
particularly about MDMA neurotoxicity.
MAPS arranged for the entire conference to be recorded on digital video. We are
working to place selected video and audio recordings on the MAPS web site, as well as
edited transcripts of several talks and associated question and answer periods. In
addition, Dr. Julie Holland, who attended the conference and the pre-conference tour, is
editing a book on MDMA with chapters from many of the conference speakers.
Purpose of the conference
MAPS has been working since March 1998 to sponsor a study into the use of MDMA-
assisted psychotherapy in the treatment of patients suffering from post traumatic stress
disorder (PTSD), to take place in Israel at Ben-Gurion University of the Negev, under the
direction of Dr. Moshe Kotler and Dr. Adam Darnell. MAPS has pledged $50,000 for this
study, $12,500 of which has already been paid. MAPS' long-term strategy prioritizes the
effort to open the door to MDMA psychotherapy research in several countries in addition
to the United States. In this way, we have the greatest chance that at least one such study
will be approved and will yield data that can then be shared with other regulatory
agencies. In the best of circumstances, MAPS will be able to sponsor and coordinate
MDMA-assisted psychotherapy research in several locations around the world.
The primary purpose of the conference was to present the latest scientific information
about the risks and benefits of MDMA to Drs. Kotler and Darnell, and to officials in the
Israeli Ministry of Health and Anti-Drug Authority. MAPS' goal was to fully inform the
protocol design and approval process in Israel regarding the proposed MAPS-sponsored
MDMA/PTSD study, in the belief that a balanced assessment of the research data would
lead to approval of the study. The secondary purpose of the conference was to foster
the exchange of data and international collaborations between research teams involved in
all aspects of the study of MDMA in human subjects, thereby expediting the pace and
quality of research.
The conference was budgeted at $50,000. MAPS was able to raise $45,500 in new funds
specifically for the conference, from Tim Butcher, Ami Shinitzky, Robert Barnhart, Jeremy
Tarcher and the S. Family Foundation. This large investment and the support MAPS
obtained from funders demonstrates the importance we all place on obtaining permission
to conduct research into the psychotherapeutic benefits of MDMA.
View pictures that go with this article
The pre-conference tour
I've come to realize that scientists frequently need to meet each other in person before
they come to fully believe what they read in scientific journals. Research, particularly at
the advancing frontiers of knowledge, is still as much art and ambiguity as it is fact and
clarity. In order to give MDMA researchers a chance to visit with each other in an informal
setting, and to make coming to the conference potentially more attractive, MAPS organized
a six day pre-conference tour of Israel, with participants charged a break-even cost. The
tour involved four days in Jerusalem, one day in the Galilee and the final day in desert
areas on the way to the Dead Sea Hyatt, where the conference was held.
I am proud to say that 33 people participated in the tour; 28 adults, 4 children and one
nine-month old infant (my daughter, Eliora). Tour participants were primarily from the
US and Spain, with one person from the Swiss MDMA research team. I was particularly glad
that three of the people involved in the Spain MDMA/PTSD project and their families came
along for the tour. I have been engaged for some time in an e-mail discussion with Jose
Carlos Bouso, a Ph.D. candidate who is developing the MDMA/PTSD study in Spain, and
actually committed $22,000 to his project before ever meeting him in person. The
opportunity to get to know Jose Carlos and his medical advisors was one of the most
important aspects of the tour.
One participant in the tour, Lew Seiden, Ph.D., University of Chicago, needed to use a
wheelchair. Not surprisingly, the Old City of Jerusalem was not built to accommodate
wheelchairs, which didn't exist when the city was founded or when it was rebuilt after
being destroyed numerous times. It was therefore necessary to carry Lew around the Old
City, which is built into a hill, with a shifting team of four people around each corner of
the wheelchair. This was actually a bonding experience for us all. I was reminded of
Jerusalem in days of old, with the Kings being carried about in their chairs. Fortunately,
Lew's laborers were permitted ice cream, water and rest breaks.
Accomplishments: Israeli perspective
On the first night of the conference, the only event on the schedule was an opening
dinner. Dr. Carmi Margolis, an administrator at Ben-Gurion University of the Negev,
welcomed everyone to Israel on behalf of the University. In his talk, he explained that one
of the goals of the Medical School at Ben-Gurion University was to foster international
scientific exchange. He also pointed out that, though he still needed to be convinced, he
had an open mind about the possible therapeutic benefits of psychedelics. Dr. Kotler and I
enjoyed dinner with Dr. Margolis, his wife and his daughter. After a spirited and well-
received discussion of the use of MDMA and LSD in treating PTSD, I gave Dr. Margolis a
copy of Shivitti: A Vision, an autobiographical story about the LSD-assisted
psychotherapy of a concentration camp survivor suffering from PTSD. The author of
Shivitti has also written several other powerful books about his experiences during
the Holocaust and is well known is Israel. Dr. Margolis appreciated the gift and offered a
short description of the Kabbalistic meaning of Shivitti, which is sort of an incantation
making the spiritual world manifest physically. I think our dinner made Dr. Margolis
more comfortable with Dr. Kotler's efforts to initiate MDMA/PTSD research.
Rather than start with my own impressions of the impact of the conference itself, I'd
like to quote from an e-mail message I received after the conference from Dr. Jorge Gleser,
Director of the Department for the Treatment of Substance Abuse, Israeli Ministry of
Health, who attended the conference along with several other staff members from his
Department. Dr. Gleser remarked:
"I would like to thank you and MAPS again for the meeting and for allowing and
supporting the participation of other Israeli colleagues. The meeting did change our point
of view towards MDMA and similar substances and served to reduce the stigma. We will
try to advance some of the projects like the treatment of PTSD with MDMA, the treatment of
opiate [withdrawal] with Ibogaine and possibly with Ketamine."
The reference to the ibogaine project refers to a study in heroin addicts that Dr. Kotler
is trying to obtain approval for in Israel, to be funded by Humatech, a company founded by
Bob Sisko (see MAPS Bulletin Vol. IV, No. 2, pp. 15-23). To support the case for the
approval of the Israeli ibogaine study, I invited Dr. Deborah Mash, University of Miami, to
speak at the conference about her experience studying the use of ibogaine in the treatment
of heroin addicts. Dr. Mash's talk was inspiring. She made a strong argument for the
expansion of ibogaine research. Dr. Kotler's protocol is now being reviewed by the Israeli
Ministry of Health, with eventual approval considered likely.
Dr. Gleser's comments about ketamine research need a bit of elaboration. At the
conference, I handed Dr. Gleser and his associates copies of Dr. Evgeny Krupitsky's latest
paper about his three year MAPS and Heffter Research Institute (HRI)-funded study
investigating ketamine-assisted psychotherapy in the treatment of heroin addicts,
conducted at the Leningrad Regional Center for Alcoholism and Drug Addiction Therapy.
Dr. Krupitsky's study shows promising results at the six-month follow-up. Dr. Gleser was
interested in learning more about the ketamine research, even though there is no effort
being made at present to start such a study in Israel.
As a result of the conference, Dr. Gleser invited MAPS to organize a series of
presentations on psychedelic research, especially related to the treatment of addiction
and to drug policy, at a large international conference on addiction scheduled for
November 6-9, 2000, in Jerusalem. The conference is being sponsored and organized by
the Israeli Ministry of Health's Department for the Treatment of Substance Abuse, the
Anti-Drug Authority, the International Society of Addiction Medicine, and the Israel
Society of Addiction Medicine. I have already sent Dr. Gleser a proposal for seven
speakers that MAPS would like to sponsor at the conference, with the proposal currently
under review by the conference organizing committee.
One unexpected benefit of the conference was the opportunity to offer international
support from the assembled scientists for the Department for the Treatment of Substance
Abuse's plans for a heroin maintenance study in Israel. In this proposed study, which
builds on the pioneering Swiss heroin maintenance program, heroin will be administered
to heroin addicts in an effort to see if health problems and crime can be reduced. Also to
be investigated is the extent to which the treatment team is able to motivate and assist
addicts to quit their habits entirely.
Also present at the conference was Dr. Rachel Hamberger, the chief scientist for the
Israeli Anti-Drug Authority. She seemed quite interested in the presentations at the
conference and offered encouragement for the protocol. I introduced Dr. Hamberger to Dr.
Franz Vollenweider, University of Zuerich, who spoke to her about the research
opportunities at his world-class lab, his need for more staffing, and his interest in
offering internships to Israeli scientists/physicians in training who could go to Zuerich
for six months to assist in research. I mentioned to Dr. Hamberger that Drs. Kotler and
Darnell had wanted to send some psychiatrists they train to Switzerland to fulfill their
six-month research requirement, but hadn't been able to find anyone who was fluent in
German, required to understand and sensitively assist subjects undergoing psychedelic
experiences. Dr. Hamberger felt she might be able to find a qualified German-speaking
scientist/physician and indicated an interest in trying to find out whether the Israeli's
expenses could be paid for by some combination of the Israeli Ministry of Health, the
Swiss National Science Foundation, and MAPS, if need be.
Another Israeli present at the conference was Dr. Raphael Mechoulam, Professor at
Hebrew University. Dr. Mechoulam is internationally famous for his research into the
constituents of marijuana. He was the first to isolate THC from marijuana and the first to
identify the endogenous cannabinoid neurotransmitter, which he named anandamide. Dr.
Mechoulam spoke about clinical research with cannabinoids, reinforcing the idea that
clinical research with Schedule 1 drugs like marijuana and MDMA is important and can be
conducted safely. Dr. Mechoulam has also been involved in Israel in determining which
scientific studies can ethically be conducted in humans. In the US, these decisions are
made by committees called Institutional Review Boards (IRBs) and in Israel by Helsinki
Committees, after the Helsinki Accords which were drafted after the Nazi concentration
camp experiments. As a result of the conference, Dr. Mechoulam now has a more
comprehensive and accurate view of the risks of MDMA to human subjects.
Near the conclusion of the conference, Dr. Moshe Kotler told me that he thought the
conference was very impressive and a major success. His final words to me were, "Let's
move forward." Coming from an Israeli with the rank of General (Moshe was chief
psychiatrist for the Israeli Defense Forces), I feel confident that our forward motion will
eventually lead to approval for the study.
One major goal of the conference was to improve the chances of approval for the
MDMA/PTSD protocol. That goal was clearly accomplished.
View pictures that go with this article
Accomplishments - Spain
Three MDMA researchers from Spain participated in the conference and came on the
pre-conference tour with their spouses, and one daughter. After meeting the Spanish team
in person, I am more enthusiastic than ever about their proposed study into the use of
MDMA in the treatment of PTSD in rape victims. They have a long history of sophisticated
and important drug research, much of it funded by government grants.
The conference also provided the opportunity for Moshe Kotler, Adam Darnell and Jose
Carlos Bouso to meet informally to discuss protocol design issues and scientific
collaboration between the two teams working
to obtain permission to conduct MDMA/PTSD studies.
The meetings between the Israeli and Spanish teams were a very important benefit of
the conference, and hopefully are just a beginning in a long relationship. Jose Carlos'
study, one of MAPS' highest priority projects, has already been submitted to the Spanish
Ministry of Health for review. We are all hoping for the best.
Additional accomplishments: my perspective
On a personal note, the complex logistics worked smoothly for bringing together 33
people for the six-day tour, 15 more people for from 1-3 days in Jerusalem, and scientists
from 8 countries for the conference. In a delightful moment, the people on the pre-
conference tour met up at the top of Masada with the 15 other people who came from
Jerusalem in a separate bus, just as I had hoped. In my hopefully accurate estimation, I
was Exhibit A for ability to perform complex tasks after taking lots of MDMA, instead of
being Exhibit A for MDMA brain damage.
The most important new data about MDMA neurotoxicity was presented by Dr. Franz
Vollenweider, University of Zuerich. Franz reported on a study of MDMA neurotoxicity in
MDMA-naive subjects, to which MAPS donated $6,000. The study involved the use of PET
scans to measure serotonin uptake sites, which are reduced by MDMA neurotoxicity. Dr.
Vollenweider's team and Dr. Ricaurte's team at Johns Hopkins are the only groups in the
world using PET scans to measure serotonin uptake sites. However, there is a crucial
difference between the methodology of the two groups. Dr. Vollenweider studies the effects
of the actual administration of pure MDMA to MDMA-naive subjects. Dr. Ricaurte does not
administer MDMA but studies people with extensive use of Ecstasy (which is sometimes
MDMA and sometimes not), frequently taken in rave environments. Dr. Ricaurte then
compares the results of the Ecstasy users to that gathered from matched controls.
Methodologically, Dr. Vollenweider's study design is more reliable in that it eliminates
problems related to inexact matching between MDMA and control subjects. Furthermore,
Dr. Vollenweider's study directly relates to determining the risk to research subjects in
studies examining the therapeutic use of MDMA, where one or several doses of MDMA will
be administered to MDMA-naive patients. Dr. Ricaurte's studies in polydrug users who
have taken MDMA from 75 to thousands of times are valuable because this sort of study is
most likely to show reductions in serotonin nerve terminals, since subjects have such high
exposure to MDMA. However, this study is of less relevance to understanding the risks of
exposure to a few doses of MDMA in a clinical research context.
Dr. Vollenweider reported on data gathered from several subjects who were given three
PET scans, before, during and one-month after the administration of 1.5 mg/kg of MDMA.
No reduction of serotonin uptake sites were found at the one-month follow-up. Dr.
Vollenweider actually reported a slight increase, which he said was not statistically
significant and represented normal variation in the PET scanning technique.
Dr. Vollenweider also reported on the results of a series of other biological and
psychological tests administered to a total of about 50 MDMA-naive subjects, with the
tests administered to subjects before and after one MDMA session and before and after one
placebo session. There was no evidence of functional or behavioral consequences due to
MDMA, either between the tests given before and after the administration of MDMA or
between the people whose first session was MDMA or whose first session was the placebo.
Lew Seiden, Ph.D., University of Chicago, presented data from animal research that
showed conclusively that serotonin reductions are related to core body temperature, with
higher ambient temperatures producing hyperthermia which makes one vulnerable to
serotonin reductions. This research calls into question risk assessments for clinical
research subjects based on data from rave-goers who take MDMA in high-ambient
temperatures, exercise vigorously, and sometimes do not consume sufficient fluids. In
contrast, clinical research contexts involve the administration of MDMA in temperature-
controlled settings, to people who are resting in bed and are supplied with fluids. This
data about the importance of ambient temperature requires a revision of the
understanding of the mechanism of MDMA-related neurotoxicity. Some drugs which we
previously thought blocked neurotoxicity through a specific pharmacological mechanism
turn out to actually block neurotoxicity through non-specific blocking of
Matt Baggott, researcher on the UC San Francisco MDMA research team, presented a
complicated new analysis designed to compare human and animal data in order to
extrapolate from animal data what dose in humans would cause the first signs of any long-
term reductions in serotonin levels. Matt's approach is based on comparing similar blood
levels of MDMA, as determined in pharmacokinetic studies, as opposed to basing
comparisons on body weight or body surface area. According to this analysis, 5 mg/kg in
humans is the equivalent of the lowest dose that has been shown to cause any long-term
reductions in serotonin levels in rats. This is not necessarily the same as the highest dose
that will not cause neurotoxicity, which is not known. This is only a preliminary approach
and there are lots of assumptions in this model that are based on incomplete data. Most of
the rat neurotoxicity data was collected before the importance of hyperthermia was
appreciated. Therefore, these doses may cause serotonin reductions only in certain
environments or with certain behaviors. Significant amounts of individual variability also
need to be taken into account. A 5 mg/kg amount of MDMA is the same as taking more than
twice as many milligrams as pounds of body weight, for example 5 mg/kg in a 150 pound
person is 340 milligrams. A standard therapeutic dose of MDMA is 100-125
According to Baggott's estimates, Dr. Vollenweider's preliminary finding of no
apparent long-term reductions in serotonin uptake sites in humans from a dose of 1.5
mg/kg was not surprising and is consistent with the animal neurotoxicity data.
Dr. Efi Gouzoulis-Mayfrank presented data from a study comparing MDMA-using ravers
with two control groups, one with subjects who had used cannabis but not MDMA and
another with control subjects who did not use drugs. The mean estimated cumulative total
dose of the MDMA-using group was 93 pills, the mean duration of regular use was 27
months. The only differences found were in certain subsets of memory and executive
functions, with the MDMA-using group performing somewhat lower. According to Dr.
Gouzoulis-Mayfrank, these differences were statistically significant but clinically
insignificant, meaning that neither the subjects nor the testers could tell the groups apart
in normal social situations or in life performance. Dr. Ricaurte and Dr. Bolla's studies of
memory function in MDMA users (MAPS Bulletin
Vol. IX No. 3 pp. 6-8) are also
statistically significant but clinically insignificant. Possibly confounding any causal role
of MDMA in the memory findings is that these studies may be measuring effects of the
Ecstasy raver lifestyle (lack of sleep, poor nutrition, heavy use of other drugs not matched
by the controls groups) or of possible preexisting factors. However, the study of Dr.
Gouzoulis-Mayfrank included no unusually heavy or poly-drug users. At present, the only
evidence in humans for functional consequences from regular exposure rates to MDMA is
from data that are not clinically significant and are not conclusively proven to be due to
MDMA. The minimal findings in these studies of Ecstasy users is reassuring. In summary,
there are no data showing that one or few doses of MDMA in a clinical research context
bear substantial risks for long-term harms from possible neurotoxicity.
The consensus of the conference was that MDMA research in humans is important, that
it can be conducted safely, that there are sufficient anecdotal reports and case histories of
the therapeutic use of MDMA to justify research into the therapeutic use of MDMA, and
that the risk of neurotoxicity is clearly outweighed by potential benefits in patients who
are either terminal or have failed on conventional medications. Studies in MDMA-naive
subjects or in patients who are not terminal or have not already failed on conventional
medications were supported by most but not all conference participants.
MAPS' Israel MDMA conference helped improve the chances that the MDMA/PTSD study
will be approved in Israel, fostered international collaboration and data sharing, provided
an opportunity for MDMA psychotherapy protocols to receive thoughtful critiques, and
generated a willingness among several researchers to provide letters of support to national
regulatory bodies for MDMA psychotherapy protocols.
After reflection, I believe that the many months of MAPS' staff time that were invested
in this conference, along with roughly $50,000, will prove to be an excellent investment
that has played a major role in bringing us into the promised land of MDMA
View pictures that go with this article