Pubdate: Wed, 25 Feb 2004
Source: Chronicle of Higher Education, The (US)
Copyright: 2004 by The Chronicle of Higher Education
Contact:  http://chronicle.com/
Details: http://www.mapinc.org/media/84
Note: The transcript from the discussion at the above webpage is MAP 
archived as an exception to our normal clipping policies.
Cited: Multidisciplinary Association for Psychedelic Studies 
http://www.maps.org/
Referenced: http://www.mapinc.org/drugnews/v04/n320/a01.html
Bookmark: http://www.mapinc.org/mdma.htm (Ecstasy)

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A study by a prominent researcher warning of the dangers of Ecstasy was 
retracted last September after it was revealed that primates in the study 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later, the article was retracted after it was revealed that Dr.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  
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MAP posted-by: Richard Lake