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.