Withdrawal symptoms

A controversial paper on the effects of Ecstasy is retracted, fuelling debate

IN SCIENTIFIC publishing, as in surgery, retraction is a traumatic but revealing process. This week, George Ricaurte and his colleagues at Johns Hopkins University, in Baltimore, were on the operating table. Almost a year ago, this team of neuroscientists published a paper in Science which showed that methylene-dioxy-methamphetamine—a recreational drug more commonly known as Ecstasy—killed off brain cells that produce and respond to dopamine. This chemical is a neurotransmitter (a molecule that carries signals from one nerve cell to another). A lack of it is involved in Parkinson's disease, which causes tremors and twitches. The paper sparked debate both in the laboratory, where many other researchers questioned its methods and findings, and in the wider world, where the opponents of Ecstasy seized on the results as further proof of the drug's dangerous effects.

In the current issue of Science, however, Dr Ricaurte and his team retract these results. The reason is painfully simple: they injected the wrong drug into the monkeys in their experiments. The mistake apparently emerged when the researchers tried, and failed, to reproduce their findings, and also tried to extend them by feeding Ecstasy to monkeys rather than injecting it, in order to mimic more closely the way humans take the drug. When they realised they were using a different batch of Ecstasy for this work, they went back to look at their older supply. Unfortunately, the original vials had been discarded, but they did have vials of another drug, labelled as methamphetamine (a similar, but not identical, molecule), delivered by the same supplier on the same day. When tested, these vials were found to contain Ecstasy, not methamphetamine, which suggests that the labels had been switched.

Dr Ricaurte retracts the findings of his original study (re-published by MDMA.net) in the current issue of Science. See also the work of Charles Grob and Andy Parrott.

Further proof came through animal testing. Although, like the vials, the monkeys used in the original experiments were long gone, some of their brains had been frozen for further research. When these were analysed, they were found to contain methamphetamine, not Ecstasy.

Not sorted

The proponents of Ecstasy have used this sorry turn of events to argue that the drug is not as dangerous as its opponents would have it. They accuse Dr Ricaurte of rushing his original research into print, under pressure from politicians keen to clamp down on Ecstasy—a charge that he denies. Charles Grob, a psychiatrist at the University of California, Los Angeles, who is an advocate of the medical use of Ecstasy, argues that this mistake calls the whole body of Dr Ricaurte's research into question and that the wider issue of Ecstasy's long-term effects on the nervous system should be re-examined.

While many see this as a dark day for Ecstasy research, others are more sanguine. According to Michael Morgan, an experimental psychologist who works at the University of Sussex, in England, the vast body of research into the effects of heavy Ecstasy consumption suggests that serotonin, another neurotransmitter, is the molecule most affected by the drug, and that it is this which may be responsible for many of the long-term problems exhibited by some users. (These include memory loss, anxiety, impulsive behaviour and depression.) Dr Ricaurte's suggestion that dopamine levels are also directly affected by Ecstasy threw the field into confusion. What little clarity there is about the effects of the drug, Dr Morgan hopes, has now been restored with Dr Ricaurte's sad, but commendable, retraction.

That said, dopamine may well play a secondary role in the long-term effects of Ecstasy. Dr Morgan points to clinical research by his group, and recent brain-imaging studies by Rainer Thomasius at University Hospital Hamburg-Eppendorf in Germany. These suggest that although serotonin may be central to Ecstasy's long-term effects, other neurotransmitters could be involved as well. Indeed, work by Andy Parrott at the University of East London, also in England, has found that 14% of “light” Ecstasy users (those who have taken the drug fewer than ten times) and 38% of those with more than 100 lifetime exposures, complain of tremors and twitches that could be associated with changes in dopamine activity. There are also reports of doctors who are treating young Ecstasy users for Parkinson's disease. But because Ecstasy users often take other drugs as well, and sometimes have pre-existing psychiatric problems which spur them to take Ecstasy in the first place, pinning these effects specifically on Ecstasy will require much more research.

There is no doubt that using Ecstasy carelessly can kill by causing people to overheat and drink too much fluid. That lowers their blood's salt concentration and throws their hearts out of kilter. But whether light recreational use has long-term effects on the brain, and how, is still hotly debated. What is needed is a study of new users, to look at problems as they develop, and weed out other factors that might account for them. Until this is done, the dispute over Ecstasy will rave on.

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Ecstasy: 'neurological time bomb' or labelling error?