ECSTASY ON THE BRAIN

Some say it will kill you or poison your brain, others that it's a safe
enough high if you take precautions. Despite official campaigns
highlighting ecstasy's dangers, the drug has never been more popular with
clubbers. Are they recklessly risking brain damage or worse, or sensibly
ignoring anti-drug propaganda. David Concar looks for the facts behind the hype

IN A SMALL clinic in Charleston, South Carolina, preparations are under way
for a landmark medical experiment. As New Scientist went to press, the
researchers were still waiting for final approval from an ethics panel. But
if all goes to plan, a dozen or so traumatised victims of violent crime
will soon be given a mind-altering substance in a bid to release them from
their terrible fears.

The trial is funded by the Multidisciplinary Association for Psychedelic
Studies, a maverick body founded by an enthusiast with a drugs policy PhD
called Rick Doblin. And if it seems a little hippy-trippy, appearances are
deceiving. Double-blinded and placebo-controlled, the trial is, on paper at
least, as rigorous as anything a pharmaceuticals company might carry out.
What's more, every detail has been approved by stern-faced government
regulators at the US Food and Drug Administration.

Their colleagues over at the Drug Enforcement Agency are furious, and it's
not hard to see why. The pill in question is ecstasy, otherwise known as
MDMA. And in normal circumstances of course, government authorities do not
see swallowing it as a remedy for the psychological effects of crime. They
regard it as a crime itself, not to mention a threat to people's health.
Especially in the US, where the drug's rising popularity has been rattling
law enforcers.

Indeed, fearing a crack-style epidemic, the US government has in the past
couple of years stiffened legal penalties and stepped up efforts to
publicise the dangers. Dose for dose, ecstasy offences are now punished
more harshly in the US than those involving heroin. Radio ads and posters
in malls warn of memory loss. The hugely influential National Institute on
Drug Abuse near Washington DC has even been distributing postcards
picturing brain scans. The cards set a normal brain, looking bright and
radiant, alongside a "brain after ecstasy" -- a lump with dark blotches
that look like holes.

In other words, while bona fide doctors supported by one US government
agency get ready to dole out E as a medicine, other agencies are doing
their utmost to warn teenagers off the drug. It's all very confusing. And
you'll find equally mixed messages elsewhere. Take Britain. Last year the
government introduced a tough new law making it a crime for club owners to
permit the use of ecstasy on their premises. This year it issued a booklet
telling the same club owners to lay on chill-out rooms, treatment areas and
plentiful supplies of water. If not a green light to ecstasy use, then
surely a sign of greater tolerance... or maybe not. For in Britain, the law
puts ecstasy on a par with heroin and crack cocaine. And while some senior
British police officers think that's wrong, the government insists it will
not be downgrading a substance that the evidence to date shows is so dangerous.

But just how dangerous is it? In recent years the US government has spent
tens of millions of dollars, way more than anyone else, trying to pinpoint
the harm. And according to its most senior scientific officials there's no
longer any doubt: even if it doesn't kill you, ecstasy is a recipe for
lasting, possibly permanent, damage to the serotonin neurons in the brain
that are involved in everything from memory and mood to sleep, sex and
appetite. In a hearing before the Senate last July, NIDA's then director
Alan Leshner stated: "There is across-the-board agreement that brain damage
does occur." Research, he added, has "unequivocally shown that MDMA
literally damages brain cells".

New Scientist went behind the scenes to talk to a wide range of
researchers. We found that no such agreement exists. Nobody claims ecstasy
is benign. It isn't, and never could be-no drug is. Yet few of the experts
we contacted believe that research has yet proved ecstasy causes lasting
damage to human brain cells or memory. Far from it, according to some, the
highest-profile evidence to date simply cannot be trusted.

Blotchy brain scans of ecstasy users have become the ace card in public
information campaigns. In the US, they also strongly influenced the move to
tougher sentences. Yet impartial experts told us that the scans, though
published in a respected journal, are based on experiments so fundamentally
flawed they risk undermining the credibility of attempts to educate people
about the risks of drugs. "The brain scans do not prove ecstasy damages
serotonergic neurons," said one researcher, who asked for anonymity.
"Whether to use the evidence is therefore a matter of politics rather than
science."

Our enquiry doesn't prove ecstasy is harmless to brain cells. But it does
raise questions key to the future of drugs policies the world over. When
the evidence about the safety of an illicit drug is complex and disputed,
who gets to decide which findings are sound enough to influence policy? How
active should government policy makers be in screening out unreliable
findings? And how open should they be about scientific dissent?

Some things about ecstasy are reasonably certain. Like many legal drugs, it
affects the way brain cells handle the neurotransmitter serotonin. The
cells in question are rooted near the brain's base but have long nerve
fibres that fan out into higher regions. Here the fibres meet and
communicate with other nerve cells, "messaging" them by squirting serotonin
into the tiny joints, or synapses, that connect all nerve cells in the brain.

MDMA turns these squirts into surges. It makes cells shoot virtually their
entire load of serotonin and reabsorb it unusually slowly. And the drug
does this by latching onto certain proteins dotting the surfaces of the
nerve cells, called serotonin transporters. The normal job of these
proteins is to absorb serotonin back into cells. MDMA makes the proteins
work in reverse and pump the stuff out. It's not all the drug does to brain
chemistry, but most scientists think it's the key to E's loved-up sensations.

And the key, too, to the drug's less desirable effects. Some short-term
problems are no longer in serious dispute. In recent years it's become
clear that ecstasy can make it dangerously difficult for some people to
pass water, and help to bring on sudden and sometimes fatal heatstroke,
especially in hot dance clubs (see "Life and death on the dance floor", p
31). Most experts also agree that by temporarily depleting the brain of
serotonin, MDMA can leave users vulnerable to the mid-week blues. Yet
neither of these risks, say experts, has created a serious public health
problem. The mood swings are comparatively mild, and, despite the drug's
massive popularity, ecstasy deaths remain extremely rare: downhill skiing
kills more people. Even Britain's leading ecstasy expert, John Henry of St
Mary's Hospital Medical School in London, thinks the risk of sudden death
has been "overemphasised".

What most worries scientists like Henry is the possibility that hundreds of
thousands of ecstasy users could be storing up mental health problems for
the future. Are they? George Ricaurte and Una McCann, a husband-and-wife
team at Johns Hopkins University in Baltimore, Maryland, have led the way
in trying to pinpoint the drug's longterm impact on the brain. And after
nearly 15 years of research, they are convinced the drug can damage
serotonin synapses and nerve fibres. Indeed, they say, really persistent
users even risk succumbing to "pruning", in which the longer, thicker
serotonin nerve fibres in the brain wither and are replaced by a denser
growth of spidery, shorter ones. In short, swallow E week in week out and
the fine structure of your brain may never be the same again.

Hardly a basis for pressing for lower legal penalties. But how good is the
evidence? For years it came exclusively from animal experiments. Typically,
researchers give rats or monkeys high doses of ecstasy, leave them a few
weeks, months or even years, and slice open their brains. It's not easy to
scrutinise entire nerve fibres and synapses directly, but scientists can
take a snapshot of the serotonin transporters dotted around the brain to
see if any are missing or out of place. Many studies have found such
changes, but some haven't, and the experiments continue to this day. So
does the debate about what they really mean (see "Brain drain?").

In 1998, however, the case against ecstasy took a dramatic new turn.
Ricaurle's team published a paper in The Lancet reporting what looked to be
lasting brain damage in people who use ecstasy. This time the evidence was
from a PET brain scanning study and seemed clear-cut. Where scans of
control subjects were alive with colour, those of ecstasy users looked dull
and dark. Ecstasy "injures brain for life", declared one of many startling
newspaper headlines.

The study involved injecting 14 people who'd used ecstasy on average more
than 100 times with chemical probes designed to stick to the serotonin
transporter proteins that ecstasy targets. Wherever the probes end up they
give off a detectable but safe radioactive glow. If ecstasy destroys
serotonin synapses and fibres, the reasoning went, there ought to be fewer
transporters for the probe to find in these damaged brains, and they ought
to glow less. Sure enough, the brains of the ecstasy users did on average
glow less than those of control subjects.

At the time, not every expert was convinced this deficiency was evidence of
longterm damage by ecstasy. The drug users used lots of substances and the
researchers reported no urine or saliva tests to prove they were drug-free
at the time of the scan. Some critics even suggested the subjects could
have been naturally deficient in serotonin synapses. But as it was
impossible to prove these alternative explanations, the bleaker view of the
brain scans took hold.

Soon the scans were at the centre of the US government's campaign on the
dangers of club drugs and featuring in TV documentaries. The scans also
featured prominently in the official report by the US Sentencing Commission
that last year led to longer prison sentences for ecstasy offences. The
brains scans, it claimed, showed "that users had a significantly reduced
number of serotonin transporters throughout the brain".

And soon too other brain-imaging teams were attempting to build on the 1998
finding. A year later, researchers from the Royal Edinburgh Hospital in
Scotland also published a paper claiming that regular ecstasy users have
fewer serotonin transporters in the brain-further evidence, they concluded,
of the drug's "neurotoxicity".

More recently, a team led by Liesbeth Reneman and Gerard den Heeten of the
Academic Medical Centre in Amsterdam wanted to find out if heavier users of
ecstasy lose more serotonin synapses than lighter users. To this end, they
scanned the brains of four groups: moderate users of ecstasy who claimed to
have taken no more than SO tablets in their lifetime; heavy users who
claimed to have taken hundreds; heavy users who claimed to have abstained
for at least a year; and a control group. "Our results," the team concluded
in a paper published last year in The Lancet, "indicate that women could be
more susceptible than men to the neurotoxic effects of MDMA".

It was another worrying finding that on the face of it seemed to back up
the crucial 1998 study. Except that on close inspection, there were
discrepancies and contradictions. This time, the male ecstasy brains in the
study lit up just as much as the control brains, and it was only after
analysing the female brains separately from the male brains that the
researchers found anything different about some of the women. The brains of
the heavy female users, it turned out, did light up less than those of the
moderate female users and female controls. Yet even these "damaged" female
brains performed no worse than the brains of the supposedly healthy male
non-users.

It's a confusing picture, so New Scientist asked some leading independent
scientists to look at the evidence afresh. What we learned was that the
probes used in the scanning studies have serious deficiencies and that
despite the poster depiction of "your brain on ecstasy", there never
was-and never has been -- a typical scan showing the typical brain of a
long-term ecstasy user.

"There are no holes in the brains of ecstasy users," says Stephen Kish, a
neuropathologist at the Center for Addiction and Health in Toronto. "And if
anyone wants a straightforward answer to whether ecstasy causes any brain
damage, it's impossible to get one from these papers." Marc Laruelle, a
Columbia University expert on brain scanning probes, agrees: "All the
papers have very significant scientific limitations that make me uneasy."

According to both experts, the key flaw in the 1998 study is the sheer
variability of the measurements. Some control brains performed up to 40
times better than others, and even some of the ecstasy brains outshone
control brains by factors of 10 or more -- a level of scatter that both
experts say is unprecedented in this type of study. According to Kish, the
huge variations seen even in the healthy controls are a sure sign that the
probe failed to give precise and reliable measurements. It's taken years
for the problem to surface, says Kish, because the full range of the
scatter is obscured in the original paper by the unusual way the
researchers analysed their findings, converting the raw brain scan
measurements into logarithms before plotting them out.

So why the unreliability? Laruelle says the probes used in all the ecstasy
brain scan studies don't always stick just to serotonin transporters and
should therefore only be used in certain brain areas. In recent years, his
team has established that only the midbrain, thalamus and striatum have
enough serotonin transporters to give reliable readings. None of the
ecstasy studies focused exclusively on these structures. The Edinburgh team
looked only at the cerebral cortex.

Ricaurte rejects the criticism. "Variability in the data would lessen our
ability to detect differences between groups and, potentially, lea to an
underestimation of differences between MDMA users and controls," he told
New Scientist. "The fact that significant differences were found speaks for
itself."

When it comes down to it, what brains look like in a scanner shouldn't
matter as much as whether ecstasy has any noticeable long-term effect on
the way people think, feel and act. So does it? There's certainly been a
rash of papers in psychology journals suggesting ecstasy users have poorer
memories and mental reflexes than nonusers. And some of the conclusions
make disturbing reading. In one typical study, ecstasy users "showed
significantly poorer verbal fluency and immediate and delayed recall". In
another, they were "worse on a sustained attention task requiring
arithmetic calculations, a task requiring short-term memory and a task of
semantic recognition and verbal reasoning". Last year one British team even
equated such symptoms with those seen early on in Alzheimer's disease.

Yet take a closer look and, as with the brain scans, the evidence is not as
clear-cut as it sounds. For a start, in the majority of tests of mental
agility, ecstasy users perform just as well as non-users. Their reaction
times, visual memories and ability to concentrate all come out looking
normalsometimes better than normal.

In one study, psychologist Andrew Parrott of the University of East London
and his team found ecstasy users outperforming non-users in tests requiring
them to rotate complex shapes in their mind's eye. Ecstasy users also had
the edge on non-users when it came to searching a series of virtual rooms
on a computer screen to find a small red toy car. Afterwards, says Parrott,
the ecstasy users were better at answering questions about the shapes of
the rooms and the positions of their doors.

Where ecstasy users do seem to perform worse is in learning new verbal
information. In tests where people are given lists of words and then asked
to recall them later, a group of non-users might score an average of, say,
10 out of 15, while a group of ecstasy users of the same age and social
background might get 8. According to Parrott, who published the first
finding of this type in 1998, ecstasy users are also slower on average to
improve when the test is repeated. But their performance still lies well
within the spectrum of what counts as normal.

In other words, whatever ecstasy's cognitive effects may be, they are
subtle. So subtle that some experts think it's jumping the gun to blame
ecstasy when most users of the drug take many other substances. A team at
Imperial College Medical School in London recently tested three different
groups for recall, word fluency and speed of thought. One used no drugs,
another just cannabis, and the third both ecstasy and cannabis. On average,
the "no drugs" group performed the best. But the "just cannabis" people
scored no better than those who used ecstasy and cannabis. So is cannabisa
drug people often smoke to "come down" from an ecstasy high-the real problem?

Or are scientists worrying about a cognitive impairment that just isn't
there? It's an open secret that some teams have failed to find deficits in
ecstasy users and had trouble publishing the findings. "The journals are
very conservative," says Parrott. "It's a source of bias." Parrott himself
has had two papers of this sort turned down.

But is any of this a reason to dilute the ecstasy health warnings ? Surely
if there are any suspicions at all, governments and scientists should make
the strongest possible statements about risk. Perhaps. But some in the
field feel this approach carries a risk of its own. If people think the
health warnings are exaggerated or at odds with their own experience of the
drug, the authorities risk losing credibility, and with it their chance to
educate anyone about drugs.

Kish says many of the ecstasy users he interacts with already consider the
brain scans to be "simply unbelievable". Harry Sumnall, who studies ecstasy
users at the University of Liverpool, fears that by prematurely
highlighting the drug as especially dangerous, psychologists and the media
risk giving out the false message that "as long as you stay away from E,
you'll be fine".

The situation isn't helped by the impression that double standards are at
work, with one set of rules for prescription drugs and much stricter rules
for drugs used illicitly.

While scores of studies have looked for evidence of biochemical changes in
the brains of animals and people exposed to ecstasy, only a handful have
looked for anything similar in brains exposed to antidepressants and other
prescribed agents that act on the serotonin transporter. And when
scientists do scrutinise such drugs, officials don't jump so readily to
alarming conclusions.

In the 1980s, for instance, Ricaurte's team began publishing papers
suggesting a diet pill, taken daily by millions, called fenfluramine could
damage brain cells. The evidence was strikingly similar to that seen in
animals given ecstasy. But while ecstasy's "neurotoxicity" triggered
government action, fenfluramine's was brushed aside.

Of course, many people feel more comfortable about prescribed medicines
carrying risks, because they provide benefits too. That's why Rick Doblin's
efforts to turn MDMA into a prescription pill could be so crucial to
reversing the drug's demonisation. Anecdotal evidence already suggests
ecstasy could ease the pain and fears of patients with cancer or
post-traumatic stress disorder, and perhaps even help Parkinson's
sufferers. But Doblin knows only evidence from the most rigorous of
rigorous trials will do. There's no evidence, he says, that the low doses
the patients will be getting could damage serotonin nerve fibres. Yet nor
will the pills be instant miracle cures: each patient in the Charleston
trial will have 16 hours of psychiatric counselling as well.

And the hundreds of thousands of recreational users? Nobody can yet put
their hands on their heart and say that none of them will ever have serious
mental health problems, especially the heavy users, but this drug is not
new, says Doblin. "I first tried it in 1982, and many of the early users
are now in their 50s and 60s. We are not flooding into treatment centres."

SIDEBAR 1

Brain Drain?

Does MDMA harm brain cells? High doses of the drug can certainly cause
subtle longlasting biochemical changes in the brains of lab animals,
especially when injected. But should these be interpreted as evidence of
damage? And are they likely in people popping "human doses" of the drug?
The jury is still out.

To date, George Ricaurte and his team at Johns Hopkins University in
Maryland have carried out the most influential research. In the early
1990s, they began a long-term experiment with squirrel monkeys. Twice a day
for four days, they gave one group of monkeys ecstasy, another salt water.
So that their brains could be examined, the animals were then killed in
batches at varying time intervals.

After two weeks, the ecstasy monkeys had less serotonin in their brain
fluids compared with the control monkeys, and fewer of the serotonin
transporter proteins that are the main targets of ecstasy in the brain.
Ecstasy, the team concluded, had "pruned" these monkeys' serotonin synapses
and nerve fibres. After 18 months, the ecstasy monkeys still had fewer
serotonin transporters, except that there was now evidence of new serotonin
nerve fibres growing up from the base of the brain. After seven years, the
new fibres were still there but had grown only as far as the midbrain,
leaving them short of their usual summit in the cortex.

Perhaps even more worrying for clubbers is evidence suggesting that MDMA's
impact on serotonin transporters increases as animals get hotter. But not
everyone thinks losing these transporters is a sign of nerve damage: the
nerve fibres themselves may remain intact. One such dissident is James
O'Callaghan, a neurotoxicologist at the US Centers for Disease Control and
Prevention. O'Callaghan has long maintained that MDMA does not provoke the
crucial inflammatory response expected from a chemical that injures nerve
cells-the build up of star-shaped cells known as glia.

And some animal studies have failed to find any lasting biochemical
changes. A team at the US National Center for Toxicological Research in
Arkansas gave a range of ecstasy doses to rhesus monkeys but found no
significant effects nearly two years later. What's more, few studies to
date have reported long-lasting behavioural problems in animals exposed to
ecstasy.

Weeks after the Arkansas team administered high doses of the drug, their
animals performed just as well as control animals in tests of short-term
memory and motivation. A team at the Scripps Research Institute in La
Jolla, California, trained monkeys to carry out tests of memory, reaction
time and coordination and then gave them high doses. Afterwards the animals
performed the tests just as well as before.

SIDEBAR 2

Life And Death On The Dance Floor

When British student Lorna Spinks died after taking ecstasy, her grieving
parents decided to publish a picture taken minutes after her death. They
hoped Lorna's swollen, bleeding face would make others think twice before
taking ecstasy.

It didn't. Nearly two years and a couple of dozen ecstasy-related deaths
later, British youngsters are still thought to be popping anything between
half a million and 2 million tablets every weekend. The inescapable truth
seems to be that taking ecstasy is fun, and that, despite the tabloid
horror stories, clubbers think the chances of dying are vanishingly remote
and can be reduced by taking sensible precautions. But just how true is this?

In the mid-1990s, when there were thought to be around 420,000 ecstasy
users in England, the drug was listed on the death certificates of an
average of nine young people a year. So the chance of a typical ecstasy
user dying at some point in the year after taking the drug was about I in
50,000, or about five times less likely than dying in a traffic accident.
Ecstasy can come out of such calculations looking riskier than traffic, but
only if it's assumed that all the recorded ecstasy deaths in any one year
involved people experimenting with the drug for the first time -- A
possible but extremely unlikely scenario.

The annual figure for ecstasy-related deaths in Britain has crept up. The
latest, for the year 2000, is 27, the highest so far. But the fact is glue
sniffing and over-the-counter painkillers still kill more people, while
cocaine is responsible for double that number and heroin 20 times as many.
And of the 27 British deaths, 19 victims had other drugs in their system,
raising questions about which substance really killed them.

Clearly, though, ecstasy cannot be completely absolved. Why do a tiny
number of people who swallow the pills die? Genetic make-up is a likely
part of the answer. Lorna Spinks had taken ecstasy many times. The night
she died she took two pills that were just a little stronger than she was
used to and couldn't handle it. She suffered a poorly understood and
unpredictable reaction called serotonin syndrome that plunged her body into
a shivering state of rigidity and hyperthermia, leading to organ failure
and internal bleeding.

Fortunately, such marked reactions to MDMA are incredibly rare. Contrary to
popular belief, MDMA is incapable of directly triggering heatstroke in all
but a handful of unusually sensitive people. In the vast majority of cases
the direct cause of the hyperthermia is in fact the dance floor. The drug
makes users fail to notice they are overheating and dehydrating, so they
carry on dancing when they should be cooling off, says John Henry, a
toxicologist and MDMA expert at St Mary's Hospital in London. "This
explains why one tab can kill." And why studies on volunteers taking MDMA
in a calm setting fail to find any evidence of heatstroke.

Another of ecstasy's side effects is to impair the body's ability to handle
water. In experiments on volunteers, Henry has discovered that MDMA makes
the brain's hypothalamus secrete a substance known as antidiuretic hormone,
which stops the kidneys producing urine and makes it hard for MDMA users to
pass water even if they are drinking pints of it. If they do drink
excessively, disaster can ensue. In rare cases, the blood thins and the
brain swells, creating a pressure that in extreme cases pushes the
brainstem down the spine where it can no longer support breathing.

The condition is called hyponatraemia and is what killed Leah Betts, a
young British ecstasy victim, in 1995. Unlike the highly unpredictable
serotonin syndrome reaction that killed Lorna Spinks, however, it is easy
enough to avoid. Experts reckon ecstasy users can protect themselves by
drinking no more than half a litre of water per hour if they are dancing
and sweating it off, and nothing at all if they are not. What's more,
although the details are unclear, it seems young women should take extra
care since their sensitivity to antidiuretic hormone could vary over the
course of the menstrual cycle.

Research is now under way to discover the underlying factors that make
different people react to ecstasy in different ways. The way the body
metabolises the drug is likely to be crucial. For example, the liver enzyme
CYP2D6 that helps break MDMA down is inactive in up to 1 in 10 people of
European descent, which could make them especially sensitive to some of the
drug's effects.

Confusingly, it might also protect them from others. The complication is
that some of MDMAs effects are caused not by the drug but by its breakdown
products. Henry's team has preliminary evidence from rats to suggest that
one of these, called HMMA, is better than MDMA at provoking the brain to
release antidiuretic hormone. If confirmed, it could mean that people who
break down MDMA rapidly are more at risk of hyponatraemia. Claire Ainsworth

[sidebar accompanied by bargraph image]

SIDEBAR 3

The Wrong Stuff

You want a good night out, the people running the rave or nightclub don't
want you swallowing anything really nasty. So here's the deal. You provide
a crumb or two of your ecstasy pills for the checkers to inspect and test.
They tell you what they think the pills contain and what the risks of
swallowing them might be.

Depending who you talk to, it's either a pragmatic way to curb the harm
ecstasy tablets can do or a dubious step toward quality control for illicit
drugs that can only create more users. France, Germany, Austria and Spain
all unofficially allow drug screening in certain clubs. Even in
tough-on-drugs America it happens at certain raves. But the British
government says the tests are imprecise, unnecessary and likely to create a
false sense of security amongst users. Who's right?

Stories about dangerously contaminated ecstasy pills are certainly
exaggerated. Unlike drugs sold in powdered form, such as speed or heroin,
it is hard for dealers to "cut" ecstasy tablets with toxic adulterants such
as bleach. The problem is that what is sold as ecstasy is often not MDMA at
all. Synthesising MDMA can be tricky, especially as the chemicals required
are controlled by governments. So some suppliers fake ecstasy by mixing
concoctions of other ingredients, some of them a lot more toxic than MDMA.

The most notorious is PMA, or paramethoxyamphetamine. Small doses produce
mild hallucinations and euphoria, but take more and it leads to vomiting
and hyperthermia. Worse, as the euphoria is milder and slower to appear
than with MDMA, some unwitting users take extra pills to get a better high.
At least nine deaths in the US and three in Europe have been blamed on PMA.

A foolproof argument for allowing chemical testing in all nightclubs? Not
quite. The commonest method, called the "Marquis test", involves scraping
some of the pill into a colourless reagent containing sulphuric acid and
formaldehyde. MDMA turns the reagent violet/purple and then slowly
blue/black. The problem is that some ingredients in fake ecstasy pills
trigger the same colour changes. Others, such as PMA, cause no colour
change at all, so tablets made of these will pass the test provided they
contain a trace of MDMA.

In clubs in Bern and Vienna, experts are now trialling a more accurate
technique known as high-performance liquid chromatography. But the machines
cost some ?35,000 apiece.

The Netherlands has taken a different tack. While stopping ad hoc chemical
testing in nightclubs, it runs an official pill testing service at 23 drug
prevention and treatment centres. Dutch ecstasy users can take their pills
to any of the centres, where trained employees note down the pills' colour,
dimensions and logo, and run a Marquis test. They then log on to a database
that holds details of all the pills tested more rigorously by an
independent lab service in the previous six weeks. If the pill doesn't
match any of the known profiles, it can be sent off for rigorous testing
and added to the database. Any evidence about potentially dangerous pills
is available to clubbers within days.

According to a 1997 survey of Dutch ecstasy users, pill testing neither
encourages nor discourages use. But Raymond Niesink, who coordinates the
Dutch scheme, believes it has saved lives. "There are no PMA victims in the
Netherlands," he says, unlike in Belgium.

In the US, voluntary organisations such as DanceSafe continue to check
pills at raves and send samples for analysis. But they operate in a grey
area of the law. In Britain, nobody is systematically analysing any of the
ecstasy that's out on the street.