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Ecstasy may damage brain physical defenses { November 14 2005 }

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Ecstasy may damage the brain’s physical defences
16:53 14 November 2005 news service
Alison Motluk

The drug ecstasy reduces the brain’s defences, reveals a new study of rats, leaving it vulnerable to invasion by viruses and other pathogens.

The researchers behind the study warn of "clinical considerations which may apply to the treatment of people who abuse MDMA". For example, anaesthetics could find it easier to penetrate the brain, "greatly increasing the risk of unwanted sedation". And they say infections could cause permanent damage to brain cells or alter the ability of the brain to function normally.

The brain is protected by a fence of tightly packed cells, called the blood-brain barrier. This prevents all but the smallest molecules from passing through. But the new experiments show that MDMA – the chemical name for ecstasy, or “e” – somehow forces open that barrier, allowing larger molecules access to the brain.

Bryan Yamamoto at Boston University, US, and colleagues gave rats four doses of MDMA over 8 hours. “We were trying to approximate a human dosaging pattern,” says Yamamoto. The scientists also injected a blue dye, made of molecules too large to get into the rats' brains under normal circumstances.

One day later, the researchers found the dye had made its way into parts of the brain, such as the caudate and the hippocampus. Ten weeks later, despite no further doses of MDMA being given, new injections of dye were still passing through the blood brain barrier.

Ten weeks in rats could be considered the equivalent of five to seven years in humans. “It does seem to be a very protracted opening,” says Yamamoto. But, as yet, he is unable to say for sure whether the breach is permanent.

Prior protection
Other new research on MDMA has investigated "binges" of ecstasy-taking in rats. Scientists found that rats exposed to many single doses of ecstasy as adolescents are protected from much of the harm caused by e-binges as adults.

Jerrold Meyer at the University of Massachusetts in Amherst, US, and colleagues gave pre-pubescent rats a dose of ecstasy, then repeated the dose every five days, until young adulthood – a total of six doses.

After a period to allow the rats to clear the drug from their bodies, they received up to four times the previous dose spread only over a few hours. The researchers monitored such things as body temperature, body weight and behaviour. A week later, their brains were studied for signs of neurotoxicity.

Typically after a big ecstasy binge, animals suffer hyperthermia, fatigue and lethargy and sustain damage to serotonin axons – the long fibres extending from serotonin-containing neurons. All these features were observed in control rats.

But the rats that had been pre-exposed to the drug were spared these symptoms, including damage to their serotonin system. “Exposure does have this powerful effect to protect animals,” says Meyer.

Therapeutic use
Whether any prior exposure, or only exposure during adolescence, can protect humans this way is not yet clear. “My hunch is that it might be specific to the adolescent period,” Mayer says.

But the mechanism remains a mystery. Among the possibilities is that the pre-exposed animals may be metabolising the drug more quickly, he says, or they may be ratcheting up antioxidant activity in their bodies, or they may be modifying their serotonin receptors.

Not all research on MDMA is into its negative effects. Stephanie Linley at Florida Atlantic University in Port St Lucie points out that the drug is now being investigated for clinical use in diseases as wide-ranging as schizophrenia, post-traumatic stress disorder and terminal cancer.

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