Your Brain on Bad Science

Not everyone was surprised this past weekend when Dr. George A. Ricaurte of the Johns Hopkins University School of Medicine published a retraction in the journal Science of an earlier paper asserting that MDMA, a.k.a. Ecstasy, negatively affected dopamine function in two species of nonhuman primates. Writing with four other authors, including his wife, Una D. McCann, Ricaurte admitted that “the drug used to treat all but one animal . . . came from a bottle that contained d-methamphetamine [a known dopamine toxin] instead of the intended drug, racemic MDMA.” Ricaurte et al. blamed the lab for mislabeling the two drugs, but other experts in the field have raised questions about studies involving Ricaurte before.

According to some scientists, Ricaurte, who gets substantial grant money from the National Institute on Drug Abuse (NIDA), has often omitted data that might undermine his case that even low or occasional doses of MDMA can cause brain damage — an argument that has been used to halt potentially significant research into MDMA’s therapeutic applications.

Rick Doblin, director of the Multidisciplinary Association for Psychedelic Studies (MAPS), maintains that Ricaurte’s reporting errors date back to at least the mid-’80s, when Ricaurte began conducting “no-effect” level studies on rats and monkeys to determine MDMA’s lowest toxic dose. In one study for which Doblin helped acquire the monkeys, Ricaurte “started out administering 2.5 milligrams per kilogram given every two weeks for eight doses,” Doblin explains. Finding no evidence of brain damage, Ricaurte increased the dose to 5 milligrams per kilogram — two to three times higher than the equivalent human therapeutic or recreational dose. This time the monkeys’ brains showed signs of damage to their serotonin neurons. But when Ricaurte published his results in 1988, he focused solely on MDMA’s toxicity, omitting any data establishing a safe dose of the drug.

Later, Ricaurte collaborated on an “L-tryptophan challenge” study with scientists at Yale University. The subjects for the study, who were recruited from an earlier study conducted while Ricaurte was at Stanford in the mid-’80s, were flown to Connecticut from the West Coast and given intravenous L-tryptophan — the amino acid present in large amounts in dairy products and turkey, which many people take to help them sleep. He then submitted the jet-lagged and sedated subjects to intelligence and memory tests.

Still, the subjects performed admirably. In a letter to Doblin, Charles A. Opsahl, a psychologist in Connecticut who evaluated the results, wrote that “most subjects evaluated had IQ scores in the above average range or higher.” There were, however, some dips in memory performance tests, which Opsahl suggested may have been “related to travel fatigue, being in a new environment, or being stressed in some way . . .”

But when the researchers, including Ricaurte, reported on the study in 1992, Doblin was stunned: The published results made no mention of those alternative explanations. Also absent was any mention of where the subjects came from: According to Dr. Charles Grob, a psychiatrist at Harbor UCLA Medical Center who secured the first FDA approval to study MDMA in humans and has critiqued Ricaurte’s work extensively in print, the subjects had already been shown in an earlier study to have low levels of the neurotransmitter serotonin, which could contribute to neurological function. “He recruited from the low end of the spectrum,” says Grob, “and never admitted his pre-selection bias.

“This is typical of Ricaurte’s research,” says Grob. “Methodological flaws, sleight of hand, sensationalizing to the media.” Not only has Ricaurte’s work obstructed serious research into the therapeutic potential of MDMA, “but it’s distracted us from the real risks associated with MDMA — such as hyperthermia and cardiac arrhythmia — that we should be studying.”

Even the infamous NIDA post card featuring positron emission topography (PET) scans Ricaurte performed in 1998, comparing a slice of serotonin-rich brain to a depleted one, was based on distorted evidence, says Doblin. “The way to do [that post card] would have been to pick the person closest to the middle of each group — users and nonusers — and compare the two. Instead, they picked people at the extremes. They did it for dramatic effect.”

Ricaurte was returning from Switzerland and could not be reached for comment, but he has insisted that the retraction of the dopamine study has no bearing on his earlier research. Last year he told the Weekly, “There are not many drugs of abuse that have the potential to actually damage brain cells. MDMA is uniquely dangerous.” Doblin has long insisted just the opposite — that pure MDMA not only is uniquely benign but has enormous potential for therapeutic applications.

Doblin is now hoping Ricaurte’s retraction will help jump-start the MAPS-funded and FDA-approved study of MDMA’s potential in treating post-traumatic stress disorder, which has been stalled by controversy. “What’s happened is that Ricaurte has stopped research into therapeutic effects of MDMA because he’s become a spokesperson for the whole scientific effort. His entire career is now based on the presumption that one dose of MDMA is dangerous.”