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'Ecstasy: a Human Neurotoxin?' A Novartis Foundation Meeting


"Warning: 'Ecstasy users risk memory loss and depression"
The Evening Standard, 4/12/98

"Ecstasy use may cause brain damage, say scientists"
The Guardian, 5/12/98

So, what was the trigger for this latest media frenzy over the long-term dangers of ecstasy, so soon after the furore surrounding Professor Ricaurtes study in the Lancet?

On Friday 4th December The Novartis Foundation held a discussion meeting in London entitled:

"Ecstasy (MDMA): a Human Neurotoxin?".

Attendance at the meeting was by invite-only and was limited to scientists conducting research into the field.

There were four speakers, all known for their research pointing out the potential dangers of MDMA:

Professor Andy Parrott (Dept. of Psychology, University of East London)
Dr Valerie Curran (Dept. of Clinical Psychology, University College London)
Professor Una McCann (Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, USA)
Professor George Ricaurte (Dept. of Neurology, Johns Hopkins School of Medicine, Baltimore, USA)
Dr Fabrizio Schifano (Servizio Tossicodipendienze, Padova, Italy)

There was also an impressive list of discussants, which included toxicologists, neuroscientists, psychologists, and researchers into the potential uses of MDMA within psychotherapy.

A substantial part of the day was taken up with a press conference (transcript of press conference) and press lunch. But were the press given the whole story?

Presentation were made by Professor Parrott, Professor Ricaurte and Professor McCann, with Professors Ricaurte and McCann focusing on their recent research results. Abstracts of their presentations.

The basic message of the press conference presentations was that MDMA has been shown to be neurotoxic in all animal studies, that the indications are that a single dose of MDMA causes neurotoxicity in the human brain, and that the long term functional consequences of this neurotoxicity for MDMA users are potentially depression, mood swings, memory problems, sleep disturbance, and anxiety disorders. The methodological difficulties present in this kind of research, which make interpretation more difficult, (such as polydrug use by MDMA users, and unusual lifestyles with reduced nutrition and adverse rest patterns) were mentioned by Professor Parrott as an important caveat to any findings, but this was not picked up on by the press.

A number of the meeting 'discussants' were present at the press conference and, while questions and answers were supposed to be limited to the press and speakers, felt compelled to offer an alternative viewpoint to the doomsday scenario.

Following Professor McCann's comment that "one dose is sufficient to produce a neurotoxic lesion", Dr Madhu Kalia, of Jefferson Medical College in Philadelphia, USA, intervened to question the terminology being used. She pointed out that the changes are pharmacological, that the drug acts by depleting serotonin and that

"the validated measures that Dr McCann has used are actually measures of depletion of the 5-HT transporter and metabolite. They are not measures of brain lesions. There is no evidence that there are real lesions in the brain. There is no evidence of gliosis, that there is any scarring, that any neurons are lost...we are not seeing brain lesions in animals".

This exchange of views was stopped by the meeting's organiser as "not press conference material".

An important issue raised in the press conference was the difficulty of reaching conclusions from data produced from retrospective research on humans, rather than prospective research. This is the difference between studying the brains of humans who say they have taken MDMA in the past (whether recently or not) and studying the brains of humans before and after actually giving them MDMA. In the first case there are clear methodological difficulties. For instance, differences in the brains of MDMA users, compared to a non-using control group, could be pre-existing. Another problem is a lack of certainty about what the users have actually taken. This question was raised and Professor Ricaurte pointed out that while he would like to test samples of the substances taken by subjects, this is no longer possible given the number of subjects travelling to his lab from overseas and the obvious difficulties around having subjects bring illegal substances into the country.

However, despite the clear drawbacks to retrospective research, prospective research is not been undertaken because of perceived ethical difficulties. Professor Ricaurte mentioned two problems he saw with this kind of research on humans. Firstly, he believed it would be unethical to ask subjects to participate in a study the purpose of which would be to "see whether or not we can destroy serotonin nerve terminal in your brain". It was pointed out that this is happening on dancefloors all over the country every weekend, and that there was unlikely to be a shortage of people willing to volunteer for MDMA research. Indeed, it was said that not to do this kind of research should be seen as unethical.

Professor Ricaurte's second problem centred around what he saw as the lack of medical necessity to test MDMA in this way - "there is still no documented evidence that MDMA has any medical utility".

Dr Charles Grob, an American psychiatrist who is looking at the possible uses of MDMA within therapy (particularly for treating post-traumatic stress disorder) intervened to point out the catch 22 nature of this argument - "there's no documented evidence because putative medical application has not been put to rigorous testing. There have been no authorised, sound, methodological investigations, in large part because of the concerns you are arising about neurotoxic potential". There is no evidence because the studies have not been done but the studies cannot be done until there is some evidence to support them.

Transcript of Press Conference
Abstracts of Presentations
Press Coverage

 

4 December 1998