September 27, 2002

Study in Primates Shows Brain Damage From Doses of Ecstasy

By DONALD G. McNEIL Jr.

The amount of the drug Ecstasy that some recreational users take in a single
night may cause permanent brain damage and lead to symptoms like those of
Parkinson's disease, a study in primates has found.

But critics say that the monkeys and baboons in the study were given huge
overdoses of the drug and that the kind of damage the researchers found has
never been found in autopsies or brain scans of humans who took large
amounts.

Dr. George A. Ricaurte of the Johns Hopkins University School of Medicine,
who led the study, said its most disturbing finding was that just two or
three Ecstasy tablets can damage the cells that produce dopamine, a brain
chemical that helps control movement, emotions and the ability to feel
pleasure.

To mimic the aging process, he gave some primates another drug that destroys
dopamine production, and found that those that had taken both Ecstasy and the
dopamine-killing drug moved less than those given only the dopamine reducer,
suggesting that Ecstasy users could suffer the same consequences as they
aged. The study appears today in the journal Science.

But a psychiatrist from Bellevue Hospital in New York and the leader of an
organization that wants to test the psychiatric benefits of Ecstasy said Dr.
Ricaurte's doses " delivered by injection, not tablet " were far greater
than a human user could stand. Two of the 10 monkeys and baboons died of
heatstroke, they noted, and 2 more were in such distress that they were not
given a third shot.

Though heatstroke and dehydration are problems at dances where Ecstasy is
used, human deaths from the drug are relatively rare. If 20 percent of all
users died, these critics said, it would not be as popular as it is.

Three shots in six hours "was like 10 tablets in six hours, and the bulk of
Ecstasy users at raves take 1.5 to 2.5 doses a night," said the Bellevue
psychiatrist, Dr. Julie Holland, who is the editor of a book on Ecstasy.
"Also, that's about $250 to $300 worth at street prices, and that's a lot of
money.`

Dr. Una D. McCann, a psychiatrist and an author of the new study along with
her husband, Dr. Ricaurte, said the doses were "actually slightly less" than
a human might take. "I can't explain" why the two animals died, she said,
"but if you're doing studies with only four or five animals, it's not
appropriate to draw conclusions like `one out of five will die.' "

Ecstasy, also known as MDMA, is a methamphetamine whose users describe an
overwhelming sense of peace and friendship for others, as well as the energy
to dance for hours. Chronic users report never being able to repeat the
pleasure of their first highs, and the drug apparently depletes the brain's
reserves of dopamine and serotonin, which communicate pleasurable feelings.

Dr. Ricaurte has done research on the dangers of Ecstasy for years. In 1995
he found that it caused the brains of rats and squirrel monkeys to form
abnormal connections in the serotonin-producing pathway. That, he theorized,
could lead to problems like chronic depression.

Some of the same critics, including Rick Doblin of the Multidisciplinary
Association for Psychedelic Studies, who has long sought government approval
to test Ecstasy's usefulness for post-traumatic stress disorder, argued then
that Dr. Ricaurte's test doses were 45 times what humans normally take.

In 1998, Dr. Ricaurte's review of brain scans of 14 humans who had taken
Ecstasy up to 400 times found that they had fewer serotonin-absorbing brain
cells than nonusers.

His new study "sends an important public health message " don't experiment
with your own brain," said Alan I. Leshner, a former director of the National
Institute on Drug Abuse and a supporter of Dr. Ricaurte's work. Dr. Leshner
is now chief executive of the American Association for the Advancement of
Science, which publishes Science magazine, but took pains to say he "had
nothing to do with the decision to publish the study."

The study was important, he said, because it found similar results in two
species and showed that Ecstasy could damage two different brain pathways.

Dr. Leshner was reluctant to endorse a warning that one-night Ecstasy users
could suffer parkinsonism in later life. "I don't like hyperbole," he said,
"whether it's in the direction that this drug is safe or that it's not."

Ecstasy, which was invented 80 years ago, was used as a stimulant and in some
psychiatric research until 1985, when it was put in the same legal category
as heroin and cocaine. A measure before Congress called the Anti-Rave Act
seeks to penalize promoters of parties where "club drugs" are used, just as
law enforcement officials sought to penalize landlords whose buildings were
used as crack houses.

Critics said the study was timed to influence the Congressional debate, but
Dr. McCann denied it. "We had no political intentions," she said.

Mr. Doblin, who has been seeking Food and Drug Administration permission
since 1985 for legal psychiatric testing, said that similar drugs, like the
amphetamines given to schoolchildren for attention deficit disorder, also
affected dopamine levels but showed no evidence that they lead to the tremors
or rigidity of Parkinson's disease.