Researchers retract study tying Ecstasy to Parkinson's|
Hopkins doctors used mislabeled drugs in tests
Frank D. Roylance and Dennis O'Brien
September 6, 2003
Researchers at the Johns Hopkins Bayview Medical Center have been forced to retract a highly publicized paper linking the drug Ecstasy to serious brain damage after discovering that they had actually administered a different drug to most of the animals in their study.
In a retraction scheduled for publication next week in the prestigious journal Science - which ran the original results a year ago - the team led by Hopkins neurologist George A. Ricaurte says that a vial labeled as MDMA, the active chemical in Ecstasy, actually contained methamphetamine, a similar but chemically distinct drug known as "speed." Researchers said the vials were apparently mislabeled by a supplier.
The retraction states that the mislabeled drug was used on all but one of the 15 primates in the two-year study. Although the methamphetamine would be expected to have effects similar to Ecstasy's, the researchers said, the results of the study were invalidated by the labeling error.
Influential and widely publicized at the time, the Hopkins study was seized on by health officials who argue that the drug causes serious, long-term brain damage, a conclusion that is not universal in the scientific community. The study was funded by the National Institute on Drug Abuse (NIDA).
Minor corrections are common in Science, but Ginger Pinholster, director of public programs for the journal, said she could recall "maybe a handful" of retractions in the past four years.
The professional journal, with 140,000 subscribers, is published by the American Association for the Advancement of Science and is one of the most influential publications of its kind the world. Pinholster credited the scientists with "doing the right thing."
"These researchers should be applauded for coming forward the way they did," she said.
Dr. Una D. McCann, one of the study's co-authors, said she worries that the false results may mislead other researchers and erode public confidence in drug research. "We're very regretful about what it might have done, not only to our scientific colleagues, but to the public at large," she said.
In their original paper, the researchers said that when MDMA was given to squirrel monkeys and baboons, it produced the same sort of brain damage seen in people who suffer from Parkinson's disease.
They said the doses they used were similar to those taken by young people during all-night "rave" parties - three doses at three-hour intervals.
In their retraction, the scientists said the labeling error does not invalidate past studies concluding that Ecstasy can have serious effects on brain function in rats. McCann said the error does mean that it remains to be established whether Ecstasy has similar effects on primates.
According to their retraction statement, the scientists began to suspect something was amiss after the original study was published when they couldn't reproduce the results using orally-administered doses of the drug instead of injections.
Realizing that they were using a new batch of MDMA, they had it tested and found it authentic. So they returned to the original study and found records showing that both drugs - MDMA and methamphetamine - had been ordered on the same date and arrived at the lab from the supplier int he same package. The two bottles had different labels and batch numbers. They were stored in a locked laboratory safe.
Suspecting that the labels had been switched, the scientists had the contents of the original methamphetamine vial tested. It proved to contain MDMA. But the original vial of MDMA had been used up and discarded, so the researchers tested frozen brains from two of the animals that had originally received the supposed MDMA. They contained no trace of MDMA but did contain traces of methamphetamine.
The two drugs were supplied to the Hopkins lab by Research Triangle Institute International (RTI) of North Carolina and paid for under a contract with NIDA.
"We know all the supplies come from RTI. We don't know where the errors occurred," said Beverly Jackson, a NIDA spokesman. "Everybody needs to take a close look at what happened."
Representatives from RTI could not be reached for comment last night.
Research into Ecstasy has been controversial, with some physicians arguing that funding targeted at finding problems with the drug is politically motivated and that neurological damage has been exaggerated.
Dr. Charles Grob, a Hopkins-trained psychiatrist on the faculty at the UCLA School of Medicine and longtime critic of Ecstasy research, said that many studies of the drug at Hopkins have been flawed, targeting the drug's ill effects and discouraging research into its possible therapeutic value.
Grob said MDMA may have applications for patients suffering from severe anxiety or trauma. "It's been a seriously hyped issue," he said. "We have a drug war going on, and it's hard to shift gears and examine a drug in an entirely different context, where it could be useful for psychiatric treatment," he said.
The other investigators in the Hopkins study were Doctors Jie Yuan and George Hatzidimitriou of the Hopkins Department of Neurology and Branden J. Cord of the Department of Neurosciences.