ECSTASY RECONSIDERED

Wednesday, February 25, at 2 p.m., U.S. Eastern time

A study by a prominent researcher warning of the dangers of Ecstasy was
retracted last September after it was revealed that primates in the study
had been injected with a different drug. What does this mean for the future
of Ecstasy research? What are the implications for U.S. drug policy?

In an article published in the September 27, 2002, issue of Science
magazine, George A. Ricaurte, an associate professor of neurology at the
Johns Hopkins University, warned of new dangers attached to the use of
Ecstasy, including the risk of severe brain damage and debilitating
neurological diseases, even from just one night of taking the drug. A year
later, the article was retracted after it was revealed that Dr. Ricaurte
had mistakenly tested the effects of methamphetamine, not Ecstasy.

The episode cast doubt not only on Dr. Ricaurte but also on the National
Institute on Drug Abuse, which has supported his research for years.
Critics have said the federal agency seeks studies to confirm its view of
the drug's exceptional menace. In the wake of the paper's retraction, what
is the future of Ecstasy research? What do we know for sure about the drug?
Have its dangers been overstated by government agencies and the news media?

Rick Doblin, president of the Multidisciplinary Association for Psychedelic
Studies, is an advocate of the therapeutic use of drugs like Ecstasy and
marijuana. His organization is sponsoring the first government-approved
study of Ecstasy for the treatment of post-traumatic stress disorder. He
has long criticized what he calls the "demonization" of the drug by
agencies like the National Institute on Drug Abuse. He has also assailed
the work of Dr. Ricaurte.

A transcript of the chat follows.

Thomas Bartlett (Moderator):

Hello everyone. I'm Tom Bartlett and I'm a reporter for The Chronicle --
I'll be moderating today's chat. Thanks to all of you who have already sent
in questions. Keep 'em coming!

Our guest today is Rick Doblin. Welcome, Rick. Okay, let's get started.

Question from Oliver Markley, Professor Emeritus, University of
Houston-Clear Lake:

There is an old Latin phrase that translates as "Who will regulate the
regulators?" My question is, "How was the process of program funding and
review of this controversial research done?" "Was it a 'level playing field'?"

Rick Doblin:

I'll take on the easy question first, about funding. So far, all funding
has come from tax-deductible donations to MAPS from private individuals and
family foundations. Over the last four years we have raised about $250,000
and have spent $150,000 to get the study designed and approved by FDA, DEA,
and IRB, to create our systems for data gathering and monitoring, and to
outfit the MDMA treatment facility. At present, research into the
therapeutic use of MDMA is too controversial for the major foundations.
MDMA is not perceived as potentially profitable by the pharmaceutical
industry since MDMA is off-patent and use patents are not available since
the therapeutic use has been widely reported publicly and is therefore in
the public domain. NIH funding from the National Institute of Mental Health
(NIMH) is not available until we have some promising pilot data which we
can't have until we conduct the initial pilot study. Donations can be made
on the MAPS website :) The more difficult question is about the review of
the protocol. FDA courageously demonstrated that it's primary emphasis was
on the science behind protocol design and the risk/benefit analysis, rather
than the politics. However, the numerous IRBs that we tried to work with
focused mostly on politics but the final IRB did put the science first. The
DEA clearly put politics first. A complete record of our interactions with
FDA, IRBs and DEA is available on the MAPS website.

Question from Nick, U. of Washington:

Previous research has (perhaps falsely) argued that use of MDMA can reduce
serotonin activity levels in the brain. Have there been studies that have
tried to establish a link between MDMA use and memory retrieval in the long
run? If so, what are some significant results? Also, what are implications
toward attention deficits (if any)?

Rick Doblin:

The best controlled studies of MDMA and long-term cognitive processing
(memory and executive functioning) demonstrated no clear association
between serotonin levels and performance but some association between
amount of MDMA consumed and performance. MAPS has helped sponsor the first
MDMA/memory study in a population of MDMA users who had very minimal use of
other drugs. This study has not yet been published and is being used as the
basis for a large grant application to NIDA. I can say that there is no
evidence that the amounts of MDMA used in therapy will cause any
neurocognitive consequences. We are administering complete neurocognitive
evaluations in the MDMA/PTSD study pre and post.

Question from Pat Turner, U.of Edmonton:

I found that only the first few times I used Ecstasy that it was more of a
the rapeutical experience. I've consumed about 30 pills over a 5 month
period. The last time I used, I had 2 average strength pills over 4 hours
(average dose) and I completely freaked out. The previous use, I had 8
assorted pills over about 12 hours and I had an amazing time flyin' high.
My question is, Does your mood prior to consumption have any effect on the
nature of the high? Thank you

Rick Doblin:

Yes, set (which includes mood prior to consumption) and setting play a
major role in the nature of the experience. It sounds to me that you have
some emotional issues that arose during the time you freaked out that
should be looked at closely through non-drug psychotherapy or just regular
introspection. Sometimes, the most valuable benefits can come from looking
closely at the content of difficult experiences.

Question from Hank Baca, retired US Army Officer:

Since about 1000 people a year die from Aspirin Use and approx 25 died from
X use last year, are we focused on the wrong drug?

Rick Doblin:

To be fair, way more people used aspirin than MDMA. We shouldn't turn our
Drug War guns on aspirin but should work to reduce the harms of both
aspirin and MDMA though public health and harm reduction measures, not
primarily through the criminal justice system. In other areas of life, we
accept significant levels of risk. About 5 times as many people went to the
emergency room last year from cheerleading than MDMA. About 35 people die
on average per year from skiing and about the same number from scuba
diving, yet these activities are considered to offer some benefits and are
not criminalized.

Question from Thomas Bartlett:

I have one, Rick. Could you talk a bit about the use of animals in Ecstasy
research? Several researchers I spoke to for the article expressed strong
doubts about the ethics of using primates in these kinds of experiments.
What do you think?

Rick Doblin:

Personally, I believe that in some circumstances animal research can be
ethically justified. That said, I don't think that a strong case can be
made for the ethics of Dr. Ricaurte's killing of about 28 squirrel monkeys
and about 9 baboons in pursuit of evidence that MDMA hurt dopamine neurons
when there was already clear evidence from human studies that heavy MDMA
users had normal dopamine levels. Dr. Ricaurte et. al. failed to even cite
this evidence in their original Science paper.

Question from Gale Gladstone-Katz, MAPS member:

Have there been any experimental treatment/studies with MDMA (Ecstasy) on
the treatment of Schizophrenia, or other studies with regard to mental
health? And what were the results? Any referral for further information?

Rick Doblin:

No studies have been conducted on MDMA in the treatment of schizophrenia.
Dr. Julie Holland, author of Ecstasy: A Complete Guide, would like to
eventually conduct such research. Now would be a good place to announce
that we learned yesterday that DEA has given Dr. Mithoefer his Schedule I
license for the MDMA/PTSD study! This means that the first study of the
therapeutic use of MDMA has now been fully approved, about 18 1/2 years
since MDMA's recreational and therapeutic use was criminalized on July 1,
1985. Our next study, currently in the design process, will look at MDMA in
the treatment of anxiety in end-stage cancer patients. Studies with MDMA in
schizophrenia are years in the future due to limited resources.

Question from Janice Robarts Dillon, student, kaplan college:

My belief is that Ecstasy has far more repercussions for women than men. Do
you find that this is true and can you confirm my beliefs with some examples?

Rick Doblin:

I'm not sure that this is the case. The Phase I clinical trials with
MDMA didn't suggest that women were particularly vulnerable more so than men.

Question from Mike Taffe, The Scripps Research Institute:

Rick, While much of your critique of existing preclinical research has
merit, you frequently take a stance which might be described as the
opposite pole to a Ricaurte. That is, in your efforts to establish that low
doses are not likely to cause permanent damage, you seem to feel that there
is NO risk at ANY dose. So with respect to a previous question, is, in your
view, it possible that 8 typical pills consumed over a 12 hr interval would
produce lasting, possible permanent alteration to the brain? If so, is this
a likely outcome in your view? Or would it take a particularly susceptible
individual, or other factors to produce such lasting impact?

Rick Doblin:

I didn't mean to give the impression that MDMA is the one and only
drug that is risk-free. As a preface to answering your question about the
risks of brain alteration after 8 pills in 12 hours, I'd like to first make
a distinction between brain changes and functional consequences. While we
should be concerned and interested in brain changes, what matters most is
functional consequences since brain changes may reflect negative, positive
or no functional consequences. In the largest and best controlled PET study
ever conducted in MDMA users (Buchert R, Thomasius R, Nebeling B, Petersen
K, Obrocki J, Jenicke L, Wilke F, Wartberg L, Zapletalova P, Clausen M
(2003) Long-term effects of "Ecstasy" use on serotonin transporters of the
brain investigated by PET. J Nucl Medicine, 44: 375-384), heavy MDMA users
who had consumed 799 tablets on average and had abstained from MDMA for
about 18 months were the same as controls in serotonin levels. Current
users who had consumed 827 tablets on average had levels that were
identical with controls in most brain regions and only 4-6 % lower in two
brain regions. I therefore do not think that it is likely that 8 pills over
12 hours are likely to produce permanent alterations to the brain but it is
possible. New studies with more selective PET ligands are underway and the
data from them is eagerly awaited. Dr. Ricaurte and others have
convincingly shown in animals that MDMA can reduce serotonin levels in
primates that persist at least for seven years. Interestingly, no evidence
was presented that these animals were in any way functionally compromised.

Question from Thomas B. Roberts, Northern Illinois Univ.:

Do you think the Federal government has also suppressed information about
the positive possible uses of psychedelics they way they have suppressed
information about Ecstasy?

Rick Doblin:

The federal government over the last three decades has made it
exceptionally difficult, and for most of that period impossible, to conduct
scientific research into the therapeutic use of psychedelics, not just
MDMA. Government drug information dismisses evidence of therapeutic uses of
psychedelics. Right now on the website of ONDCP (the Drug Czar's office),
information about MDMA says that it once was used by therapists before it
was illegal but that therapists abandoned that use after they learned that
the MDMA experience was difficult to control and mind-altering. This is a
laughable statement since the MDMA experience isn't that difficult to
control and it was used precisely because it was mind-altering. In general,
the federal government wants us to believe that illegal drugs possess only
risks and no benefits.

Question from James Sybert, Non profit organization:

Do you think that MDMA poses a greater risk to health than moderate alcohol
consumption?

Rick Doblin:

Moderate alcohol consumption is increasingly seen as offering some overall
health benefits to users. Moderate MDMA use is probably similar in risk
level to moderate alcohol use, both with minimal risks and probably overall
more benefits than risks. When we think about the extent of binge drinking
in high school and college students, I think a case could be made that, in
actual practice, alcohol is more risky than MDMA.

Question from Kristie Stoick, Physicians Committee for Responsible Medicine:

Again focusing on the use of animals in research, do you think that
scientists will begin to move away from the large amount of animal research
done with illegal drugs, and try to focus on learning about the effects on
and treatments for the species in question: humans? I think that this
controversy sheds light on a big problem: many animals and dollars are
being sacrificed on experiments that have no bearing on the realities of
the drug war.

Rick Doblin:

Yes, now that the FDA, IRB and DEA have all finally permitted the MDMA/PTSD
study to go forward, I think we will increasingly focus on human research.
Also, as PET technology improves, we will obtain better data from humans
and need to use animal research less frequently. I was the first person
that Dr. Ricaurte gave a spinal tap to in order to assess MDMA
neurotoxicity since I felt then, and still do, that we mostly need human
research. The interspecies scaling model that Dr. Ricaurte used is not very
accurate (it predicted that that use of what turned out to be
methamphetamine in primates with a 20% mortality rate was equivalent to a
"common recreational dose regimen) so it is difficult to know what
conclusions to draw from non-human primate research.

Question from Rich Byrne, Chronicle of Higher Education:

Tom Bartlett asked about animal experimentation, and I'd like to ask about
human subjects. The 20th anniversary of Ecstasy's explosion into a
full-fledged subculture has come and gone. Are there longer-term studies of
Ecstasy use in the pipeline, and any hint as to what they might contain?

Rick Doblin:

Unfortunately, there are no efforts underway that I know of to investigate
MDMA users who started using it in the last 1970s or early 1980s. For some
time, Dr. Ricaurte and others proposed a time-bomb theory that said that
while functional consequences of MDMA were not obvious, that such problems
might become more visible after the combination of age-related serotonin
declines and insult from MDMA. However, serotonin doesn't decline that much
with age, unlike dopamine which declines to a greater extent. Studies with
long-time MDMA users would be quite important and should be undertaken.

Question from Jonathan Knight, freelance science writer:

I believe the flawed study in question was the first to suggest MDMA causes
dopaminergic nerve damage. But earlier studies have suggested it may cause
serotonergic nerve damage. Are these also flawed? Should people be
concerned about using MDMA given these findings?

Rick Doblin:

Yes, the human PET studies about MDMA and serotonin that were conducted by
Drs. Ricaurte and McCann have not been replicated by a larger and better
controlled study, the Buchert study I previously mentioned. Some level of
concern is still appropriate but the level of fear and alarm that have been
generated is excessive. MDMA does have risks, so people should always be
concerned more about emotional risks and the risks of overheating and
drinking too much water, risks which are all well-controlled in therapeutic
settings.

Thomas Bartlett (Moderator):

Thanks to all of you who asked questions -- sorry there wasn't time to get
to them all. And thank you, Rick, for your thoughts on this important issue.

Rick Doblin:

Yesterday, after trying for 18 1/2 years since MDMA was criminalized, the
first study of MDMA-assisted psychotherapy was approved. For the last two
decades, MDMA neurotoxicity was the primary area of research and the
dominant focus of public concern. I predict that the next two decades of
MDMA research will primarily revolve around therapeutic uses and functional
consequences, both negative and positive, of recreational use and other
non-medical uses such as low-doses for meditation, in promotion of
communication between people in caring relationships who don't possess a
clinical diagnosis (such as family members facing the terminal illness of
one of the members) and use in creativity studies. For more information, go
to the MAPS Web site at www.maps.org