More Chinese Whispers: the press in ecstasy over new research scare

On 6 November 97 The Independent* ran a headline story:

Proof Positive: Taking ecstasy permanently alters your brain

It went on to report that new research by George Ricaurte using PET scans had shown a difference between ecstasy users and non users. The Independent says: "though the effects of the changes could take years or even decades to show up, it is potentially serious news for the UK's estimated 500,000 regular e users who each take one or two tablets every weekend. If the brain cannot compensate for the changes caused by the drug, the long term effects could include widespread depression and even suicide.

"That is because ecstasy affects the production of a chemical that modulates how happy we feel. In effect, repeated use might leave the brain drained of that chemical. But scientists are still debating whether, over time, our most adaptable organ might make allowances even for that change".

The Independent's story was quickly taken up by other newspapers who added embellishments. The [Australian] Adelaide Advertiser claimed: "New research has produced hard evidence of horrifying side effects of the 'rave drug' taken by an estimated 600,000 Britons every week. It indicates that regular users could suffer mild mood swings, bouts of potentially suicidal depression and memory loss even years after giving up the drug."

The Independent article was based on one in New Scientist** headed

Does ecstasy cause lasting damage to the human brain?

The article says PET scans indicate that MDMA can trigger long lasting changes in the human brain. However, the article also quotes an eminent American researcher, James O'Callaghan, as saying that there is no evidence of structural damage, and the drug fails to produce the characteristic effects of nerve poisons on brain cells. Both versions quote one of the Ricaurte team members, Una McCann: "the message is that if you're going to use it, do it in moderation".

I then obtained New Scientist's source, the abstract by George Ricaurte, which concludes: "These results... suggest that humans are susceptible to MDMA-induced serotonin neurotoxicity". It also states that although animal studies show that MDMA causes long lasting deficits of serotonin, "it is not known whether humans are also susceptible to MDMA-induced serotonin injury". The word Permanent does not occur at all.

This is a clear case of Chinese Whispers: each publication adds a bit more until the original message is exaggerated out of all recognition.

Such publicity seems to polarise views: while the popular press here (and in Australia) wildly exaggerates reports of negative effects, the actual users dismiss them as shown by this quote from the MDMA mailing list:

"Omigod!!! E alters my brain. Thinking have I been what? I mean, what have I been thinking? I can feel my brain beginning to ooze out of my ears. But wait!! Maybe it's not too late!!! Maybe if I stop now I can be saved!!! Yes!!! That's the ticket. Thank you Independent!! You have just saved another raver from the evils of E."

Report from Rick Doblin of MAPS who rang George Ricaurte at my request on 10th November 97:

First, George said that their abstract did not use the word "permanent" but instead used "long-lasting." The data presented was from 14 MDMA users and 8 controls. The MDMA users were told not to use MDMA for at least three weeks before testing. Some of these subjects used MDMA up until that time period. This group of subjects were very heavy users of MDMA. Alhough George did not have the figures handy when we spoke, he thought that the group had taken MDMA an average of several hundred times or more. This study did not test for functional or behavioral consequences. George stressed that his study was preliminary, he had tested only a few people, and was still on-going.

This study does add some evidence to the claim that large amounts of MDMA can cause long-lasting reductions in serotonin. Comparing MDMA users to controls is second -best since there is always a chance that the matching process was inadequate.

The abstract which was the source of it all:

Reductions of 5-HT Transporters in MDMA Users Observed Using PET With IC-11(+)McN5652. Z. Szabo, U. Scheffel, U.McCann, R.F. Dannals, H.T. Ravert, W.B. Mathews, J.L. Musachio, G.Ricaurte Department of Radiology and Neurology The Johns Hopkins University, Baltimore, MD 21205

The recreational drug, 3,4-methylenedioxymethamphetamine (MDMA), produces long-lasting deficits of serotonin axonal markers in animals, including primates. It is not known whether humans are also susceptible to MDMA-induced serotonin injury. In the present study, [C-1](+)McN5652, a PET neuroligand selective for the serotonin transporter (5-HT), was used to assess the status of serotonin axonal terminals in MDMA users.

Fourteen MDMA users (27±10y) who had not used MDMA for greater than three weeks and eight MDMA-naive controls (38±19y) were injected with 18±1 mCi high specific activity |C-11)(+)McN5652.

Sequential PET scans were acquired over 95 minutes and regional time-activity curves were processed using metabolite corrected arterial plasma activity as the input function. Compartmental parameters of radioligand uptake (K1), release (K2) and distribution volume (DV=K1/K2) were obtained by the Marquardt algorithm. In order to achieve normal (Gaussian) distribution, the natural logarithm InDV was used as a measure of radioligand binding. Logarithmic transformation across all regions and subjects resulted in a pooled coefficient variation of 32%. MDMA subjects had a clear reduction of mean InDV in all brain regions compared to controls (MANOVA F=4.64: p=0.02). The covariance effect of age was insignificant (F=2.43; p=0.1).

These results provide the first PET evidence of reduced 5-HT in individuals with past history of MDMA use and suggest that humans are susceptible to MDMA-induced serotonin neurotoxicity.

This work was supported by grants DA 10217 and DA 06275

*The Independent is one of the UK's five national, daily, broadsheet newspapers.
** New Scientist dated 8 November 97. See their excellent website for the full text on www.newscientist.com