Ecstasy's long-term effects revealed

New
Scientist
Magazine

11 February 2009

By Graham Lawton

  
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, fueled 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.

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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."

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).

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."

The low-down on ecstasy

• Ecstasy usually refers to a compound called MDMA or 3,4-methylenedioxymethamphetamine.
• 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.
• 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.
• 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.
• 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.
• 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% of drugs seized, which is worrying because of the potential for taking very large doses.