Ricaurte was the last speaker in a session that also featured Terrence J. Monks (NIDA sponsored, I believe), who spoke about possible toxic metabolites of MDMA, and Raffael de la Torre, who presented data on MDMA pharmacokinetics as well as on some interesting unpublished experiment involving 3-day pre-treatments with paroxetine and multiple MDMA dosing in humans.
Ricaurte's retraction statement was part of his scheduled talk, so was not given in any kind of a special format. No journalists were present (at least none who asked any questions).
The chronological outline of Ricaurte's talk is as follows: He started by saying that a common toxic effect of amphetamine derivatives is "distal axotomy", and that most toxicology data available in animals and possibly in humans concerned methamphetamine. Then he showed PET scans of a meth user from a 1998 publication showing decreased dopamine transporter binding in the striatum. Next came a graph showing increasing ecstasy use between 1993-2001 in US college students and young adults. Ricaurte then made an interesting remark, calling the typical MDMA dose regimen of 2 doses per day for 4 consecutive days in animals "quite odd" (or something to that effect), presumably because it does not model human dosing patterns. He proceeded to show immunohistochemically stained brain tissues showing MDMA-induced axon loss. He listed the following factors to be considered when comparing toxicity data: species, route of administration, frequency of administration, dose. He repeated the well-known fact that 5-HT (serotonin) toxicity was found in every species examined so far, with the exception of mice.
Next he showed a slide containing only the sentence: "The neurotoxic dose of MDMA in monkey (5 mg/kg) closely approaches doses used by humans (1.7-2.7 mg/kg)."
He denied that there was much of a margin of safety for humans in these data, because if one applied interspecies scaling, a dose of 5 mg/kg in the monkey would correspond to a 1.5 mg/kg dose in humans.
He then advocated the approach of comparing MDMA plasma levels between species in order to arrive at estimates of equivalent toxic doses. He presented data from de la Torre (henceforth DLT) showing a peak plasma concentration of 441.9 ng/ml MDMA after 150 mg of oral MDMA in humans. His own data in monkeys (n=3) showed mean plasma levels of 750 ng/ml after 6-8 mg/kg of (oral? I'm not sure, but think so) MDMA, which, according to interspecies scaling, corresponds to a human dose of 2 mg/kg. However, the variability in the monkey data was quite large, ranging from about 300-1200 ng/ml.
He concluded that human plasma levels were about half of those of monkeys with MDMA-induced neurotoxicity, which, as he pointed out, is in the same ballpark, not orders of magnitude less.
Then came the retraction statement. It was rather anticlimactic, though. He showed two slides containing extracts from his official retraction statement to appear in the coming issue of Science. He introduced the issue by referring to the Science report on DA (dopamine) neurotoxicity in primates, then pointed out the unexpected nature of these results. He then explained that subsequent efforts at replicating DA toxicity using oral dosing had failed. Subsequent efforts at exactly replicating the results by using the same route of administration also failed. Ricaurte mentioned that they varied various factors such as ambient temperature in these replication experiments. Then he shortly, and in a somewhat roundabout way, addressed the mixed-up labels on the bottles containing MDMA and meth, respectively (he called it a painful experience, or something to that effect).
He hastened to stress, however, that this accident did not invalidate their earlier findings on 5-HT neurotoxicity in animals in any way.
Then it was back to normal. He again used DLT's data that showed plasma levels of about 500 ng/ml after 2 doses of 100 mg MDMA, given to humans 2 hours apart. According to Ricaurte, these levels correspond to those seen in monkeys receiving 3 times 2 mg/kg (oral, I believe) MDMA at 3 hour intervals. Again, he concluded that the margin of safety for humans was narrow.
He then showed brain images of one E user, showing either lower serotonin transporter density or lower brain activity (I'm not sure, which), and mentioned that these results had been replicated in European laboratories (he didn't say which ones).
Concluding his talk, he pointed out the complexity of factors influencing human studies, and that, therefore, animal studies were very important, since they ensured that factors such as drug purity and dose were under the experimenter's control. General applause.
In the ensuing discussion with the audience I asked the following questions (approximate wording):
"Dr. Ricaurte, I have two questions. First, I was concerned about the way you presented your data in the original Science report, and I'm more strongly concerned now in the light of the retraction of this study. For example, in that paper you failed to mention studies that had assessed DA markers in humans, although you draw conclusions regarding human users from your data. Also, you claimed that you had administered a dose in primates corresponding to a common recreational dose in humans, although the mortality rate in your animals was much higher than that commonly observed among human users. So, my first question is, weren't you a bit careless in presenting the data in such an unbalanced way? In other words, given the unexpected nature of your results, wouldn't it have been vital to exercise more caution in interpreting the data? My second question concerns your replication studies. Could you give us more details about them, in terms of when you conducted them, what oral doses you administered and at what ambient temperatures, and what DA markers you assessed?"
First, Ricaurte's answers to my second question:
Second, for his answers to my first, critical question:
A final important bit of information is that Ricaurte said they had found out about the mix-up of labels about 3-4 weeks ago (which would be beginning to mid-august).