Missing enzyme linked to toxic reaction to ecstasy

IRISH researchers are to investigate whether a specific genetic deficiency may explain why some people are having toxic, sometimes…

IRISH researchers are to investigate whether a specific genetic deficiency may explain why some people are having toxic, sometimes fatal, reactions to ecstasy.

Researchers at the department of psychiatry in St James's Hospital, Dublin, are to examine if the lack of a particular enzyme in the liver, involved in metabolising ecstasy, is a cause of severe side-effects to the drug.

The research, - which involves taking blood samples from people who have suffered toxic reactions, - is thought to be the first of its kind in Ireland.

According to one of the researchers, Dr Alan O'Donohoe, about 4 per cent of the population lack the enzyme CYP2D6. Lack of this enzyme makes it more difficult for the body to break down ecstasy. He said there was a well- documented relationship between poor metabolisers and severe reactions to anti-depressants and that the same could be the case with ecstasy.

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"When these people come across anti-depressants, or perhaps ecstasy, you might expect them, because they are not able to metabolise, to have a higher level of the parent drug in their bloodstream. If that is the case, you might expect them to suffer more from the side-effects. It would be like taking four tablets of ecstasy," he said.

`If this mechanism does play a role, what we would expect is, that rather than the 4 per cent of the population who have no functioning CYP2D6, we would expect a higher proportion of this group of patients [those suffering toxic side-effects] to be poor metabolisers", said a co researcher, Dr Michael Gill.

Their study follows on from similar research done on animals. In one experiment, the female species of a type of rat, which were poor metabolisers, reacted more severely to a dose of ecstasy than their male counterparts, who were normal metabolisers.

The researchers stress that this is only one of several possible mechanisms that might explain severe reactions to ecstasy. According to Dr O'Donohoe, a combination of mechanisms was most likely, including other factors such as the content of the tablet, the condition of the individual and the environment in which it is taken.

"Our mechanism cannot be the full explanation for one very simple reason, and that is 4 per cent of the population are poor metabolisers, but 4 per cent of ecstasy users do not suffer toxic effects," said Dr Gill.

Dr O'Donohoe and Dr Gill are anxious to collect blood samples from colleagues who come across patients suffering from toxic side-effects, medical or psychiatric, as a result of taking ecstasy.