The Agony of Ecstasy Research

Science gets recruited in the Drug War

Damaged and dead monkeys? Call in the feds! In 2002, the prestigious journal Science stunned club-going kids everywhere with a study from Johns Hopkins University researcher George Ricaurte. Probably not coincidentally, the study also furthered the cause of such draconian laws as the Reducing Americans Vulnerability to Ecstasy (RAVE) Act, which notoriously allows the police to shut down clubs and bars and prosecute their owners if any patron is caught using the apparently deadly drug Ecstasy on their premises.

Ricaurte's study, you see, found that monkeys dosed with Ecstasy—the street name for the chemical methylenedioxymethamphetamine (MDMA)—suffered permanent brain damage, exhibiting symptoms similar to Parkinson's disease. Even more alarming, two of his 10 monkeys actually died shortly after being dosed.

Even club kids who had long ago noted that 20 percent of their X-rolling compatriots weren't leaving blood on the dance floor must have had their buzz harshed by contemplating such dire results in a major peer-reviewed science journal. Well, party on. This September the magazine actually retracted the whole story. This Tuesday, The New York Times reported on the remarkable retraction and the whole sorry saga of hyped-up anti-drug research that is Ricaurte's career.

America's drug warriors, of course, embraced Ricaurte's original widely publicized study. For example, Dr. Alan Leshner, former head of the National Institute on Drug Abuse (NIDA), told the Associated Press that the Ricaurte study shows "that even an occasional use of Ecstasy can lead to significant damage to brain systems." Ricaurte wrote in Science, "The most troubling implication of our findings is that young adults using Ecstasy may be increasing their risk for developing parkinsonism, a condition similar to Parkinson's disease, as they get older."

That there seemed to be something amiss with Ricaurte's original study was noted even before the retraction by other researchers and anti-Drug War activists. The initial criticisms focused on the fact that Ricaurte injected the drug (although most users swallow pills), and that the dosages he used were much higher than in typical recreational use.

Researchers on Parkinson's disease also initially doubted Ricaurte's findings. Now that he's retracted his paper, Stephen Kish, a Toronto Parkinson's disease researcher, writes in an editorial in the November 2003 issue of Movement Disorders: "There is no epidemiological evidence that parkinsonism or any neurological abnormality, with the possible (but as yet unproven) exception of mild memory loss, is a persistent (months to years after last use) consequence of exposure to Ecstasy, a drug that has been used widely worldwide."

How could this study have gone so wrong? To start with, it studied the wrong drug. In his retraction Ricaurte admitted that the monkeys had been injected with methamphetamine instead of Ecstasy. He claimed that the mistake occurred because RTI International, the supplier of the drugs, had mislabeled the vials sent to his lab. After reviewing its records, RTI International says that it could find no evidence of mislabeling.

Why didn't peer review catch the flaws in Ricaurte's article before Science published it? Oxford University physiologist Colin Blakemore, who will soon be chief executive of the UK's Medical Research Council, suspects that the peer review may have been rushed because the editors of Science were anxious to publish the report just as Congress was considering the RAVE Act.

Indeed, this was not the first time that a Ricaurte study of Ecstasy has influenced public policy. His 1985 study that found that the longer-lasting Ecstasy analogue, MDA, reduced serotonin in rats just happened to appear as the Drug Enforcement Administration was considering banning Ecstasy by putting it on its Schedule 1 of controlled substances. That paper launched his career as a well-funded researcher on the effects of Ecstasy. Persistent problems with Ricaurte's research were extensively examined in Addiction Research by UCLA researcher Charles Grob in 2000. Nevertheless, NIDA continued to fund Ricaurte.

Since the retraction, Blakemore and others have called on Science to convene an independent inquiry into how the Ricaurte paper was approved for publication and to publish its approving referees' reports. So far Science's editor in chief, Donald Kennedy, has remained silent.

In contrast to Ricaurte's success, researchers who want to study the possible therapeutic benefits of Ecstasy have trouble getting permission to study the drug and their results are coldly received by many journals. "It's an open secret that some teams have failed to find deficits in Ecstasy users and had trouble publishing the findings," according to the New Scientist last April. Andrew Parrott, a researcher at the University of East London, told the New Scientist, "The journals are very conservative. It's a source of bias." Parrott himself has had two papers showing no significant deficits turned down.

Now that Ricaurte's work is being discredited, other researchers are investigating his earlier claims that Ecstasy depletes the neurotransmitter serotonin permanently. Recent brain-scanning research done at the University Hospital in Hamburg, Germany, found that levels of depleted serotonin are substantially restored in Ecstasy users in the long term.

Since the scandal broke, the NIDA ecstasy "fact" sheet has been quietly pulled from its website and is being updated.

Ricaurte lab's research on Ecstasy is often sloppy and it dependably finds what its Drug Warrior funders want it to find. The lab's research results need to be independently reviewed by others who have no stake or funding in agencies associated with the Drug War.

The lesson here is not that Ecstasy is safe, though evidence that it is particularly harmful is certainly lacking. The lesson is that scientific peer review, like all human institutions, is an imperfect process, sometimes subject to political pressures. When it goes wrong, as it clearly has here, how it went wrong needs to be thoroughly investigated and fixed. That's the minimum the public and the scientific community should expect from Science in this case.