MDMA neurotoxicity:
   “An ouchie for George”

Today’s New York Times has a devastating article on the research methods of George Ricaurte, whose studies purporting to show the neurotoxic effects of MDMA (“ecstasy”) were used to support the original prohibition of the drug and have since been used to support stiffer penalties, ancillary laws such as the RAVE Act, and suppression of human research into the drug’s potential benefits. (Full text, and a long list of errors in the story, under “keep reading.”)

As one physician commented on a listserv that follows this class of issues, the story is “what we in the pediatrics world call an ouchie for George.” And Ricaurte has another ouchie coming fairly soon, in the form of a Peter Jennings special that keeps getting delayed as the producers add more and more detail about his problems.

The new director of the National Institute on Drug Abuse, which has funded Ricaurte’s studies to the tune of $10 million over the past two decades, was clearly aware of problems with his work before the latest article, and before Ricaurte’s retractions of two of his papers, including one in Science.

But Hopkins, where the work was done, is apparently still in denial, or at least is trying to sound that way. Given the sensitivity there to human-subjects issues — a couple of years ago, the feds came close to shutting down medical research at the whole institution after the death of a healthy volunteer in an asthma study drew attention to various technical deficiencies in the Hopkins process for reviewing experimental protocols — I’d expect the dean of the medical school to be asking some very serious questions right now.

What doesn’t seem likely to happen, but should, is a review of all the legislative and regulatory decisons made, here and abroad, on the basis of what we now know to be terribly flawed studies.

We didn’t need Ricaurte’s brain imaging to tell us that MDMA does something lasting to the brains of the people who use it repeatedly: the drug’s atypical pattern of quasi-tolerance is strong enough evidence of that. (For many if not most users, the valued effects of the drug, other than its pure stimulant powers, diminish fairly rapidly, in a non-dose-reversible, non-time-reversible fashion, with cumulative lifetime dosage.)

However, open questions remain about how extensive and how damaging those changes are, and what if any steps users could take to prevent or limit them. But the exaggerated claims about MDMA’s neurotoxic effects made it virtually impossible to do the studies that might have demonstrated the efficacy of various precautions. Despite the laws, Americans currently consume tens of millions (perhaps hundreds of millions) of MDMA doses per year. It’s probable that various relatively simple steps could significantly reduce the resulting brain changes, but that possibility has never been the sort of dedicated research effort that has gone into “proving” how dangerous the drug is.

Moreover, the proposed therapeutic applications of MDMA would involve administering it on a very small number of occasions — in some cases, only once. The probability that a single MDMA dose of known purity and quantity administered under clinical conditions could do significant harm seems extremely remote. But here again, the neurotoxicity scare has prevented the relevant studies from being carried out.

With any luck, the latest scandal could lead to a more sensible set of approaches. But as Bill Bennett would no doubt say, don’t bet on it.

Full text of NYT story, with errata list

[Previous posts Sept. 9 and September 25.]

Author: Mark Kleiman

Professor of Public Policy at the NYU Marron Institute for Urban Management and editor of the Journal of Drug Policy Analysis. Teaches about the methods of policy analysis about drug abuse control and crime control policy, working out the implications of two principles: that swift and certain sanctions don't have to be severe to be effective, and that well-designed threats usually don't have to be carried out. Books: Drugs and Drug Policy: What Everyone Needs to Know (with Jonathan Caulkins and Angela Hawken) When Brute Force Fails: How to Have Less Crime and Less Punishment (Princeton, 2009; named one of the "books of the year" by The Economist Against Excess: Drug Policy for Results (Basic, 1993) Marijuana: Costs of Abuse, Costs of Control (Greenwood, 1989) UCLA Homepage Curriculum Vitae Contact: