E and the brain
Dr Ron Alcorn, a consultant psychiatrist specialising in drug misuse, reviews the evidence on whether ecstasy damages the brain
© Getty
Around the world, ecstasy use has been increasing. Many people think it is a comparatively safe drug, and there have been calls – even from 'establishment' sources such the Police Foundation – for it to be moved from Class A, which also includes heroin and cocaine, to Class B. It's said that although there have been deaths due to ecstasy's acute effects (on temperature regulation and the heart, for example), problems are very rare considering the large numbers that take ecstasy regularly.
But the government has said that it will not reclassify ecstasy. One of the reasons is that short-term dangers aren't the only cause for concern. There are questions about ecstasy's longer-term effects on the brain. Is ecstasy a neurotoxic drug – that is, a drug that damages brain cells? And if so, how worried should we be? Could the use of ecstasy be one of the most dangerous uncontrolled drug experiments the world has seen, or are some people exaggerating their claims for political reasons, as part of a wider anti-drug agenda?
serotonin and dopamine
Ecstasy or 3,4,methylenedioxymethamphetamine (E or MDMA for short) combines stimulant and hallucinogenic effects, a bit like a mixture of an amphetamine and a mild dose of LSD. It does this by altering the levels of two brain chemicals (or neurotransmitters), serotonin and dopamine. The net results are feelings of pleasure, self-confidence, increased energy, heightened sensory stimuli and a sense of closeness or empathy with others.
The potentially damaging effects on the serotonin system worry some researchers. Serotonin is linked to a number of key brain functions such as the regulation of mood, aggression, sexual drive, sleep and anxiety. It also plays a role in memory and the flexibility of thought processes (cognitive functioning). There are many serotonin pathways in different regions of the brain, and many different types of receptors within those pathways, making the serotonin system a difficult area to research.
In addition, experiments on monkeys have suggested that the brain's dopamine system can be damaged by doses of ecstasy equivalent to the doses taken by recreational users. The researchers say the study suggests that users may be putting themselves at increased risk of such disorders as Parkinson's disease.
The possibility that ecstasy might damage the brain came as no surprise to seasoned drug researchers, because ecstasy is closely related to other drugs (fenfluramine, formerly used as an appetite suppressant, and methamphetamine) that are known to be neurotoxic.
animal research
The most publicised research involves experiments on animals, including primates. As well as suggesting damage to the dopamine system, this has shown that the endings of nerve terminals in the brain (axons) in the serotonin system are changed or even 'pruned' back by ecstasy. Such changes persist for years, even after an animal has stopped being given the drug.
The most likely cause of this is 'oxidative stress'. This happens when the energy reserves of the cells are taxed, so that they have difficulty repairing themselves, or when the breakdown products of a substance such as ecstasy are not 'mopped up' and go on to damage cells.
human research
However, these findings have not been directly demonstrated in humans. Obviously it would be unethical to give humans ecstasy in controlled experiments if you suspect it may be damaging – and you can't kill human subjects and dissect their brains afterwards. So researchers are limited to more indirect methods, using scanning techniques and interviews with volunteers.
A review of the complex research literature about the human use of ecstasy finds a degree of consensus in two areas. Firstly, that there are alterations in the serotonin systems in the brains of ecstasy users (both in the short and long term), and secondly, that – in some respects – cognitive functioning is impaired in current and ex-users.
However, some scientists doubt the reliability of the brain scans and argue that the evidence from interviews and tests is contradictory. And there are other questions to be answered. For instance: do alterations to brain systems necessarily mean damage? If so, how severe is that damage? Is it permanent? Does everybody get it? And how useful is the human research when we don't always know what's in ecstasy tablets and when researchers have to rely on what people say they've taken in the past? Also, how relevant is the animal research to humans? Finally, and perhaps most importantly: do changes to the brain result in real-life problems for current or former ecstasy users?
the optimists
The optimists point out that users are not coming forward in large numbers complaining of problems, and that the problems seen are no greater than for similar stimulant drugs, some of which have been licensed as prescription medicines. Such researchers and commentators also say that problems are more likely to be seen in people who have pre-existing psychological problems or have used a lot of different drugs or have taken large amounts of ecstasy.
The animal experiments support some of these arguments. Results from animal studies are not consistent between species and depend on the drug's dose and route of administration. Many experiments have used large amounts of ecstasy given directly into the bloodstream – conditions that don't mimic the human situation. Long-term changes in behaviour, or alterations in day-to-day functioning, have been small or difficult to find, even in animals exposed to large amounts of ecstasy.
As far as alterations in the serotonin and dopamine systems are concerned, those that are sceptical about ecstasy damage use the analogy of pipes that are drained rather than broken, and point to the growing evidence of the brain's power to restore itself. They say that what is sometimes cited as brain damage (the axonal 'pruning', for example) may be an adaptive mechanism in response to the overload of serotonin and dopamine that ecstasy induces – in other words, that the system may be altered, but it may be working as well as before.
the pessimists
Other observers and researchers point out that the fact that we aren't seeing many problems in real life doesn't mean they won't emerge with time. They use the analogy of other organs such as the liver. You can get by on a fraction of your liver. The catch is when something eventually wipes out that remaining fraction. Similarly, more than 90% of brain dopamine must be wiped out before a person exhibits signs of Parkinson's disease. In other words, ecstasy users may be storing up problems for the future.
Those that believe there is real cause for concern argue that the animal research is probably a good indication of what is going on in humans. They concede that the axons may regenerate, but fear that this may result in new, abnormal connections between cells and a decreased capacity to function normally.
As evidence of this in humans, they point to the memory loss and other cognitive-functioning impairments found in ecstasy users by various research teams. In addition, there are the results from increasingly sophisticated techniques of measuring serotonin functioning in humans, and some evidence of psychiatric problems suggesting dysfunction of the serotonin system. All these elements point in the same direction, some researchers are convinced: something significant and dangerous going on.
what can you do?
So what is someone who takes ecstasy to make of all this, and is anything known about what might protect the brain from injury?
Common sense and some of the literature agree here, firstly in suggesting that repeated high doses over a long period might well cause more problems. Also, there is evidence from the animal experiments that high body temperature is related to increased damage (or alterations) in the brain. So it seems that the advice of the safe-clubbing movement, which was designed primarily to avoid short-term problems, may also be sensible for trying to prevent longer-term difficulties. That advice is that it's important to avoid getting overheated and to keep sipping water (but not more than a pint an hour). Other common-sense precautions may also be helpful: not taking repeat or 'booster' doses before assessing the impact of an earlier dose, not mixing drugs, and attending to things like sleep and a good diet so you don't get run down, for example.
Many ecstasy users are participating in clinical trials to help provide answers to some of the remaining questions, and there are also animal experiments investigating what might protect the brain. Three main areas have been examined: using drugs such as the antidepressant Prozac (a selective serotonin re-uptake inhibitor / SSRI) to replenish or regulate serotonin levels; using anti-oxidants to mop up ecstasy's breakdown products before they can damage cells; and boosting the levels of the chemical building-blocks of serotonin (5-hydroxytryptophan), either in the normal diet or as supplements. All these strategies are being employed or advocated by groups of ecstasy users, but as yet there is no evidence that they are effective in humans.
help and info
Channel 4 is not responsible for the content of third party sites.
See safer using for more about reducing the risks associated with taking ecstasy and other drugs. There's more about the effects and risks of ecstasy in the abc of drugs.
organisations
Drugscope
40 Bermondsey Street
London SE1 3UD
Tel: Office 020 7940 7500
Tel: Information Line 0870 774 3682 (Mon-Fri 10am-1pm)
E-mail: infor@drugscope.org.uk
Website: www.drugscope.org.uk
National drugs information agency with services that include a library, a wide range of publications, policy research and consultancy.
FRANK
Helpline: 0800 77 66 00 (24 hours)
Textphone: 0800 917 8765
E-mail: frank@talktofrank.com
Website: www.talktofrank.com
Provides free confidential drugs information and advice 24 hours a day. All calls are confidential. Use the website's search facility to get the contact details of organisations offering practical help and support in your area.
Release
388 Old Street
London EC1V 9LT
Legal Helpline: 0845 4500 215 (Mon-Fri 10am-5.30pm)
Heroin Helpline: 0845 4500 215 (Mon-Fri 10am-5.30pm)
E-mail: ask@release.org.uk
Website: www.release.org.uk
Offers confidential and professional legal, health and welfare advice for those who come into contact with drugs. Can refer you to local drug agencies and specialist lawyers. The website features drug facts, information on the law, and advice for dealing with the police.
websites
Crew 2000
www.crew2000.co.uk
Crew 2000 is a coalition of young people, clubgoers and others who have come together to produce real and relevant information about how to reduce the risks involved in using drugs.
DanceSafe.org
www.dancesafe.org
Lots of information about safe clubbing. Includes a slideshow with information about ecstasy and neurotoxicity.
DIY Ecstasy Information
www.sorted.org/diy/Druginfo/Ecstasy.htm
A realisitic site that offers tips for safe use of ecstasy and outlines those who are most likely to be damaged by the drug.
Ecstasy
www.ecstasy.org
ecstasy.org aims to gather and make accessible objective, authoritative and up to date information about the drug ecstasy (principally MDMA).
Erowid: MDMA neurotoxicity
www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml
An overview of MDMA neurotoxicity taken from Ecstasy: The Complete Guide edited by Dr Julie Holland.
Neuropsychobiology
http://content.karger.com/ ..
Abstracts of articles from a special edition (volume 42, no 1, 2000) dedicated to ecstasy research.
reading
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Ecstasy and the Rise of the Chemical Generation by Jason Ditton (Routledge, 2001) |
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Ecstasy: Dance, Trance & Transformation by Nicholas Saunders (Quick Trading Company, 1996) |
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Ecstasy: The Complete Guide edited by Julie Holland (Park Street Press, 2001) |
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(revised February 2003, resources updated February 2005)
