Pubdate: Fri, 27 Sep 2002
Source: San Francisco Chronicle (CA)
Copyright: 2002 Hearst Communications Inc.
Contact:  http://www.sfgate.com/chronicle/
Details: http://www.mapinc.org/media/388
Author: Carl T. Hall, Chronicle Science Writer

A LITTLE ECSTASY, A LOT OF DAMAGE?

It Hurts Dopamine Neurons, Could Raise Parkinson's Risk, Ape Study Says

Even a few hits of the mood-altering drug MDMA, popularly known as ecstasy, 
taken during a single night out can cause long-lasting brain damage, 
scientists warn in a new study.

But some researchers were skeptical that the results from the animal study 
translate to humans and said such studies discourage research that might 
lead to medical uses for ecstasy.

Scientists at Johns Hopkins University injected two or three doses of MDMA, 
each spaced a few hours apart, into monkeys and baboons in an attempt to 
mimic the typical drug-taking patterns seen at all-night raves or dance 
parties.

The study, published today in the journal Science, found evidence for the 
first time of "severe" damage to nerve cells that produce the 
neurotransmitter dopamine in a part of the brain that helps control movement.

The danger, scientists said, is that MDMA's neurological damage may stay 
hidden for years only to combine with age-related declines in the same 
brain regions, increasing the risk of Parkinson's disease and other 
movement-related disorders.

"This is a tremendously important study," said Dr. Alan Leshner, former 
director of the National Institute on Drug Abuse and now the chief 
executive officer of the American Association for the Advancement of 
Science, which publishes Science.

"It points out that even occasional use -- the equivalent of one night's 
use -- can lead to serious brain damage. How long it lasts we don't know 
yet," he said.

But others questioned the results. Julie A. Holland, a psychiatrist on the 
faculty of the New York University School of Medicine, said earlier studies 
on humans have failed to show that ecstasy causes permanent damage to 
dopamine neurons.

"It is a big leap to extrapolate what he is seeing in these primates and 
what you expect to see in Parkinson's syndrome," Holland, the author of a 
book on the risk and recreational use of ecstasy.

Once passed around as an underground psychiatric treatment, MDMA was banned 
in 1985. Lately, illicit ecstasy use has boomed in the United States. The 
popular "club drug" is touted as offering a more benign kick than cocaine 
or liquor.

About 8.1 million Americans had tried it as of 2001, up from 6.5 million in 
2000, a recent government household survey found. Another national survey, 
by the Partnership for a Drug-Free America, suggested that the number of 
teenagers who have tried ecstasy was 2.8 million, or 12 percent of students 
in grades seven to 12.

In the new study, Dr. George Ricaurte and his colleagues first injected 
five spider monkeys with two or three doses of MDMA -- 2 milligrams per 
kilogram of body weight -- spaced three hours apart. That's roughly 
equivalent to what a person might take.

One of the spider monkeys died of hyperthermia within hours of the final 
dose, and another became immobile after two doses and so was not given the 
planned third dose. All four of the survivors showed a "profound loss" of 
certain markers of cellular health in the movement- related brain regions 
when examined two to six weeks later.

Ricaurte then repeated the experiment in five baboons to evaluate whether 
the effects seen in the monkeys were unique to that species. He found 
essentially the same results -- including the death of one animal.

Earlier studies suggested that MDMA's neurotoxic effects were limited to 
other brain cells that traffic mainly in the neurotransmitter serotonin, 
which regulates mood and sensory perception. The new study is the first to 
document how the so-called dopamine system also can take a hit.

It's been known for years that certain neurotoxins are capable of 
destroying the dopamine system, creating Parkinson's-like syndromes, called 
parkinsonism, in younger individuals.

Now, researchers suggest that occasional club-drugging should be added to 
the danger list, even if definitive human studies have yet to be done. One 
possibility, experts said, is that some cases of parkinsonism may already 
have occurred, without anyone making the ecstasy connection.

But Holland said Ricaurte's study in monkeys and baboons does not relate to 
the experience of human recreational users of ecstasy. "The dose that he 
gave killed 20 percent of the animals immediately," she said. "Clearly 
these animals reacted to the drug differently than humans because not 1 out 
of 5 ecstasy users drops dead."

Also, she said Ricaurte's researchers injected ecstasy, while most human 
users take the drug orally. Drugs taken orally are less concentrated in the 
body than drugs that are injected.

The NYU psychiatrist said "there is a lot of politics involved" in 
Ricaurte's study because the government does not want to allow medical 
research with ecstasy, even though it has been approved for study by the 
Food and Drug Administration.

Ricaurte's research has been funded by the National Institute on Drug Abuse,

the agency Leshner once headed. Leshner is now chief executive officer of 
the American Association for the Advancement of Science, the organization 
that publishes Science, the journal printing Ricaurte's current study on 
ecstasy.
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MAP posted-by: Larry Stevens