Research on Ecstasy Is Clouded by Errors
December 2, 2003
By DONALD G. McNEIL Jr.
In September, the journal Science issued a startling
A primate study it published in 2002, with heavy publicity,
warned that the amount of the drug Ecstasy that a typical
user consumes in a single night might cause permanent brain
It turned out that the $1.3 million study, led by Dr.
George A. Ricaurte of Johns Hopkins University, had not
used Ecstasy at all. His 10 squirrel monkeys and baboons
had instead been injected with overdoses of
methamphetamine, and two of them had died. The labels on
two vials he bought in 2000, he said, were somehow
The problem corrupted four other studies in his lab,
forcing him to withdraw four other papers.
It was not the first time Dr. Ricaurte's lab was accused of
using flawed studies to suggest that recreational drugs are
highly dangerous. In previous years he was accused of
publicizing doubtful results without checking them, and was
criticized for research that contributed to a government
campaign suggesting that Ecstasy made "holes in the brain."
Dr. Ricaurte, a 50-year-old neurologist at Hopkins since
1988, is probably the best-known Ecstasy expert in the war
on drugs. He has received $10 million from the National
Institute on Drug Abuse, more than any other investigator
of the amphetamine analogs known as designer drugs, club
drugs or diet drugs, including MDMA, better known as
Ecstasy, and its close relative MDA.
He vigorously defends his work, saying much of it has been
confirmed by other researchers, and arguing that he is
often unfairly attacked by scientists who minimize the
dangers of designer drugs because they want to use them in
Johns Hopkins stands behind him. "The institution has every
confidence in his ability," said Gary Stevenson, a
spokesman. Of the primate study, he said Dr. Ricaurte "made
an honest mistake, then discovered it and revealed it."
But other scientists, and two human research subjects of
Dr. Ricaurte's who came forward after the retraction, say
they see a pattern of shaky research supporting alarmist
It is hard to find impartial observers in the highly
politicized debate over illegal drugs. But even three
scientists whom Dr. Ricaurte cited in his own defense said
that while his high media profile had made him a "whipping
boy" for those favoring Ecstasy research, some of his
best-known work has nonetheless been "sloppy" or "not as
methodologically rigorous as you might want."
Longtime critics are harsher.
"It's hard to trust
George," said Dr. Julie Holland, a professor of psychiatry
at New York University who has edited a book on Ecstasy and
wants to test it in psychotherapy. She accused him of
"playing games with his data" to win more federal grants by
making the drugs look bad.
Dr. Richard J. Wurtman, a prominent clinician at Harvard
and M.I.T. who has clashed with Dr. Ricaurte, accused him
of "running a cottage industry showing that everything
under the sun is neurotoxic."
For 20 years, Dr. Ricaurte has produced studies saying the
amphetamine analogs may cause the tremors of Parkinsonism,
depression and memory and sleep problems. But the consensus
among many amphetamine researchers, Dr. Ricaurte included,
is that there is no proof thus far that Ecstasy causes
permanent human brain damage. In animal studies, very high
doses have destroyed serotonin-pathway nerves, which convey
pleasure and affect memory and appetite.
Just last month Dr. Stephen J. Kish of the Center for
Addiction and Mental Health in Toronto published a review
of all Ecstasy research, including Dr. Ricaurte's, and
concluded that there was no evidence that Ecstasy caused
the tremors of Parkinsonism or any other brain damage "with
the possible (but as yet unproven) exception of mild memory
Some heavy users have memory problems, but no studies prove
the loss is permanent, or that it is caused by Ecstasy
rather than other drugs in the mix that virtually all heavy
Ecstasy - invented in Germany in 1912 by Merck
Pharmaceuticals in its search for an anti-bleeding drug -
has been outlawed in the United States since 1985, a
decision that Dr. Ricaurte has taken partial credit for.
Since about 1970, when it was called Adam, some
psychiatrists had tried giving low doses to trauma victims;
in 1985, they stopped, fearing arrest.
Dr. Holland says it relieves anxiety-provoking memories
like a sedative, but as an amphetamine, it does not induce
sleep. Patients "want to talk things through."
As a potent painkiller, she said, it also may help the
The Food and Drug Administration recently approved a study
in traumatized crime victims who have failed to respond to
antidepressants. A study of rape victims is under way in
Spain, and another one in the United States is proposed for
depressed patients with terminal cancer.
When Dr. Ricaurte's 2002 primate study was published, his
critics said he could not possibly have given "typical
recreational doses" if 2 of 10 animals died and two others
collapsed of heatstroke.
According to an annual federal survey, almost 10 million
Americans have tried Ecstasy. Few have died.
"Those dead animals should have sent up a red flag," said
Dr. Charles R. Schuster, a former director of the national
drug institute whom Dr. Ricaurte has called a mentor. "The
better part of valor would have been to not publish until
it was repeated."
Dr. Ricaurte said such arguments "do not hold water," since
animal deaths are common in amphetamine research, and two
is too few to compare to human death rates. Dr. Nora
Volkow, the new director of the national drug institute,
declined to pass judgment on his whole body of work, but
called his latest error "crying wolf and losing your
credibility." Because of it, she said, she spent a weekend
checking the agency's Web page on the dangers of Ecstasy
"to make sure it was not overstated."
The agency had already removed all current references to
another well-known study from the site, one from 1998 by
Dr. Ricaurte and his wife, Dr. Una McCann. Dr. Volkow
described it as using "methodologies that were not
Pictures from the study - PET scans of the brains of
Ecstasy users - were used on a famous postcard from the
drug agency, "Plain Brain/Brain After Ecstasy." The
postcards were distributed to thousands of teenagers and
implied that Ecstasy users had shrunken brains with holes
The study had nothing to do with holes, but with serotonin
levels, which Dr. Ricaurte found drastically depleted in 14
subjects who had taken Ecstasy 70 to 400 times.
Dr. Marc Laruelle, a Columbia University PET scan
specialist, called the work so technically flawed that it
was "something to put under the rug." He cited a recent
German study showing that serotonin decreased only modestly
and returned to normal within six weeks. The Hopkins team,
he said, presented its data in logarithmically compressed
graphs that seemed calculated to mask the fact that it had
found impossible results: its 15 "control" subjects had
serotonin levels 50 times normal.
Dr. Ricaurte defended the study, saying his recalculation
technique was common when results from two groups varied
widely, although he said he no longer used it.
Of the photos, Dr. Ricaurte said he had no control over
what the national drug institute did with his work, but he
had asked an agency official to fix their "poor quality."
In the 1990's, Dr. Ricaurte was involved in a dispute over
the danger of dexfenfluramine, another amphetamine analog
sold in Europe as a prescription diet drug.
In 1994, a company founded by Dr. Wurtman, director of
clinical research at the Harvard-M.I.T. health science
division, sought F.D.A. permission to market it in the
Dr. Ricaurte released a study saying it caused brain
damage; that was immediately disputed by an Environmental
Protection Agency study that found it did no permanent
In September 1995, Dr. Mark E. Molliver, a Hopkins
colleague who frequently published with Dr. Ricaurte,
presented slides to an advisory committee of the Food and
Drug Administration showing Alzheimer's-like brain tangles.
Dr. Wurtman, who contacted The New York Times after the
Science article retraction, said that Dr. Molliver, with
Dr. Ricaurte in the audience, misled the committee by
implying the damage was done by dexfenfluramine.
In an interview, Dr. Molliver called that "a blatant lie,"
and asserted that he had clearly said he was showing damage
done by similar drugs. Dr. Ricaurte agreed.
But transcripts of a follow-up hearing in November 1995
provided by Dr. Wurtman show that several panelists and the
F.D.A.'s expert were confused and believed that Dr.
Molliver had been showing dexfenfluramine damage.
Ultimately the drug was not approved.
For a week in 1996, Greg M. was one of Dr. Ricaurte's lab
At the time, he said, he was using large amounts of
Ecstasy, marijuana, LSD, cocaine, amphetamines and heroin.
After seeing the retraction of the primate study, he
contacted The Times, and persuaded a friend who had
accompanied him to call, too.
The two revealed their names and occupations but declined
to be fully identified for fear their former drug use would
hurt their careers. Greg is a graduate student in chemistry
at a leading university. His friend, who said he used to
follow Grateful Dead tours selling up to 10,000 doses of
LSD a month, now works at a West Coast law firm and is in
line for a federal job.
Curious to see if they had damaged their brains, and
enticed by a promise of $100 a day and a free East Coast
trip, they enlisted.
Although the two used many drugs, the research assistant
who interviewed them by phone told them what not to admit
to her if they wanted to be in the study, Greg said. They
were instructed to avoid all drugs for three weeks to avoid
tainting the study; Greg says he had used heroin five days
They and other Ecstasy users flown in from the West Coast
took memory tests while still jet-lagged, they said.
Then after lumbar punctures to check serotonin levels,
neither was given the usual night's rest to prevent fierce
headaches. They had to carry their backpacks across campus
and be wired up for a sleep study, which Greg argued could
not reflect normal sleep patterns because they were in
Both had subsequent tests after shots of morphine and a
drug, mCPP, that causes the same eyeball twitching and
teeth-grinding as Ecstasy, but none of the euphoria. Then
they had PET scans.
Dr. Ricaurte said his research protocols are approved by
university committees. He acknowledged testing sedated or
jet-lagged subjects, but argued that he had always noted
that limitation in his published papers, and switched to
testing in early mornings when jet lag was minimal. Test
subjects who get lumbar punctures are warned about
headaches, and given rest and painkillers, he said.
To weed out subjects who confound results by using other
drugs, Dr. Ricaurte said, his staff quizzed volunteers and
did blood and urine tests. His papers acknowledge that hair
tests, which can show many drugs taken even months back,
would have been more accurate. (Dr. Laruelle, who does PET
scans of Ecstasy users, rejects subjects with hair less
than an inch long.)
Told that Greg had used heroin without getting caught, Dr.
Ricaurte said that was "unfortunate." But like all drug
researchers, he said it was impossible to find heavy
Ecstasy users who used no other drugs.
His papers, he said, always warn that poor performance by
heavy Ecstasy users may have been caused by other drugs.
His critics say that such fine-print disclaimers are not
enough, that all mental tests on multiple-drug users are
pointless and cannot be used as evidence that one
particular drug damages the brain.
Greg's friend reiterated that he had been badly treated and
said he felt the research was skewed to prove he was
"Most of the people I used to do drugs with are pretty
screwed up," he admitted. "But if Ricaurte's studies are
true, Greg and I should both be dead. We ate grams a night
of pharma-grade stuff."
Nonetheless, he said: "We're fairly intelligent, rational
guys. We had a stretch of three or four years where we
really blew ourselves out. But we're still smart and
ambitious. Some of their assertions about long-term brain
damage are way off."