ECSTASY'S LONG-TERM EFFECTS REVEALED

THEY called it the second summer of love. Twenty years ago, young
people all over the world donned T-shirts emblazoned with smiley
faces and danced all night, fuelled by a molecule called MDMA. Most
of these clubbers have since given up ecstasy and are sliding into
middle age. The question is, has ecstasy given up on them? Enough
time has finally elapsed to start asking if ecstasy damages health in
the long term. According to the biggest review ever undertaken, it
causes slight memory difficulties and mild depression, but these
rarely translate into problems in the real world. While smaller
studies show that some individuals have bigger problems, including
weakened immunity and larger memory deficits, so far, for most
people, ecstasy seems to be nowhere near as harmful over time as you
may have been led to believe.

The review was carried out by the UK Advisory Council on the Misuse
of Drugs (ACMD), an independent body that advises the UK government
on drug policy. Its headline recommendation is that, based on its
harmfulness to individuals and society, MDMA should be downgraded
from a class A drug - on a par with heroin and cocaine - to class B,
alongside cannabis.

Nobody is arguing that taking ecstasy is risk-free: its short-term
effects are fairly uncontroversial. MDMA is toxic, though not
powerfully so - an average person would need to take around 20 or 30
tablets to reach a lethal dose. And for a small fraction of people,
even small amounts of ecstasy can kill. For example, around half a
million people take ecstasy every year in England and Wales, and 30
die from the acute effects, mostly overheating or water intoxication.

What has been unclear, however, is whether ecstasy use causes
long-term health problems and if so, how much you would need to take
to be at risk.

In animal studies the drug has been shown to inflict lasting damage
to the brain's serotonin system, which is involved in mood and
cognition. Imaging studies have found signs of similar damage in
human users, but there are debates over whether this is caused by
ecstasy use and whether the damage has any real-life consequences.

The ACMD based their review largely on a study they commissioned from
Gabriel Rogers and Ruth Garside of the Peninsula Medical School in
Exeter, UK. They pulled together all the research from around the
world that attempted to assess the health of people who have taken
ecstasy, and reanalysed the data from the 110 studies that dealt with
long-term effects.

They found that compared with non-users, people who took even a small
amount of ecstasy at some point consistently performed worse on
psychometric tests, which measure mental performance, especially
memory, attention, and executive function, which includes
decision-making and planning.

The most pronounced effects are on memory, mainly verbal and working
memory. While the ability to plan is somewhat affected, other aspects
of executive function are not. Focused attention - the ability to
zoom in quickly on a new task - suffers too, though sustained
attention does not.

It is a similar story with depression. "There's a small but
measurable effect," says Rogers.

These effects appear not just in current users but also in ex-users
who haven't touched the drug for at least six months, suggesting that
the problems are long-lasting. Strangely, there seems to be no link
between the quantity taken and the severity of cognitive problems,
suggesting that even a few doses can lead to these deficits.

Superficially, this adds up to a pretty depressing outlook for the
e-generation, especially those who dabbled years ago but have since
quit. Not so, says Rogers. Subtle differences in lab tests do not
necessarily translate into real-life problems: "They're statistically
significant, but whether they are clinically significant is another matter."

Subtle differences on lab tests do not necessarily translate into
problems in real life For example, there is little evidence that
people are actually affected by the memory and attention deficits
picked up in the lab tests. "They don't seem to be very big and it is
not clear that they have much effect on day-to-day functioning," he says.

Meanwhile, people who have taken ecstasy are, on average, still
within the normal bounds on standard depression tests. Although they
score worse than people who haven't taken ecstasy, the scores aren't
bad enough to warrant a diagnosis from a doctor. "There's no
indication that they are drifting out of normal functioning," says Rogers.

He also warns that his results need to be taken with a pinch of salt
because most studies are based on self-reports of ecstasy use, often
combined with other drugs and alcohol, from people who have
volunteered to take part. These confounding factors make it
impossible to determine whether you have a representative sample of
users, whether people's reported use correlates with how much they
actually took and what effects can be blamed on MDMA.

Psychopharmacologist Val Curran of University College London says
Roger's analysis "is about the best you can make of the overall
mishmash". She agrees with his conclusion that on average there seems
to be no evidence of any meaningful effects on daily life.

Others have a different take on it. Andrew Parrot of the University
of Swansea, UK, who has been studying the health of ecstasy users
since the mid-1990s says: "We see users who have taken bucket-loads
and they have very severe problems." These include memory deficits,
sleep disturbances, depression, weakened immunity and sexual
dysfunction, he says.

Based on his own studies, he believes that almost everyone who has
taken 20 tablets in total, or more, reports niggling problems in
daily life. "All fairly minor on their own, but you're ending up with
someone who is not as healthy as they ought to be," he says.

Rogers admits that because he took averages of such large numbers of
users, his analysis may have "ironed out" some of the effects Parrot describes.

Parrot also calls ecstasy a "gateway" drug. "Former users are often
heavy users of alcohol, tobacco and cannabis. When you move off
ecstasy, you look for other drugs. Ecstasy use leads to other, more
problematic drugs."

Despite this, however, results from the first "prospective" studies
are more encouraging. These studies follow a group of people over
many years and watch the effects of ecstasy unfold over time.
Crucially, they are more reliable than "retrospective" studies
because they don't rely on people remembering what they did in the past.

In 2002 a group in the Netherlands recruited 188 young people who had
never taken ecstasy but were likely to in the future. When they
retested them on a battery of psychometric tests three years later,
58 said they had taken ecstasy at least once, giving the researchers
an opportunity to compare cognitive performance before and after ecstasy.

They found that on all the tests except for verbal memory, ecstasy
users performed just as well as before, and on a par with abstainers
(Archives of General Psychiatry, vol 64, p 728). The results chime
with Rogers's conclusions: because the effect was so small - a
difference of a quarter of a word on average from a list of 15 - the
real world implications are questionable. Brain imaging revealed no
changes to the serotonin system, although there were signs of damage
to white matter and blood vessels. The practical significance of this
is not yet known (Brain, DOI: 10.1093/brain/awn255).

On all the tests except those for verbal memory, ecstasy users
performed on a par with abstainers Rogers cautions that it is too
soon to give ecstasy the all-clear in the long term, not least
because some effects on health might simply kick in even later. "It's
possible that ecstasy has horrific consequences later in life. Only
time will tell."

[sidebar]

The low-down on ecstasy

a.. Ecstasy usually refers to a compound called MDMA or
3,4-methylenedioxymethamphetamine. b.. MDMA was first synthesised by
German firm Merck in the early 20th century but only started to be
used as a recreational drug in the 1980s. c.. There are around
450,000 regular users in the US; half a million people take it each
year in the UK. A seriously heavy user might take up to 40,000
tablets in a lifetime. d.. Drug dealers originally wanted to call
MDMA "empathy" because of the powerful feelings of "loved up" warmth
it induces. MDMA is also a stimulant and a mild psychedelic. e..
Recent research suggests that most ecstasy pills on the market
contain MDMA as their only active ingredient. Toxic impurities are
often said to be common, but there is very little evidence that this
is the case. f.. Most of the ecstasy on the market is in pill form,
with each pill containing around 40 milligrams of MDMA. But very pure
MDMA powder accounts for around 30 per cent of drugs seized, which is
worrying because of the potential for taking very large doses. g.. A
single ecstasy tablet used to cost UKP15. Now they cost just UKP2.30.