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.

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.