MDMA Dose Scaling: The PK Data!

One of the fondest arguments of the MDMA/Ecstasy fan is that the doses used in animal studies are so large as to invalidate predictions or inferences about human health concerns. This most usually comes up in the long standing literature demonstrating lasting reductions in markers for serotonergic neuron function associated with MDMA. In such studies, doses of 5-10 mg/kg (monkeys) or 10-20 mg/kg (rats) are reasonably common; the regimen is often twice per day for 4 days in a row. The chronicity is debatable and indeed shorter regimens can produce significant effects, but that is a topic for another day because the complaints focus on the individual dose levels as well.
But this argument also arises when trying to figure out why three teens have died after consuming Ecstasy tablets, particularly when a medical doctor issues an opinion that it is unlikely to be 3,4-methylenedioxymethamphetamine which is at fault.
It breaks down to “Oh, c’mon! Nobody takes 5 or 10 mg/kg of Ecstasy”. The defense is based on a Pharmacology 101 concept that mg of drug per kg of bodyweight is very rough in estimating realistic drug exposure across species. Better to use a complex scaling equation, based on empirical data, that takes into account species-typical differences in drug distribution and metabolism. I overviewed the initial foofraw over the dose-scaling argument that has been subsequently used repeatedly by Ricaurte in defense of his dose selection. Although I also buy the notion that dose-scaling based on species size (mass to surface area, more or less) is important and meaningful… there are caveats to keep in mind.

Repost: Core Values of the NIH System

We’re just shy of two years past the NIH RFI on evaluating the strengths and weaknesses of the granting system. We’ve seen some changes and I thought it a decent time to revisit a post I had on what I saw as the key strengths to the system. This post went up 10 July 2007.

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Instead of only addressing the core values of the peer review system (that must be retained or enhanced), as requested in the recent RFI from the NIH, I thought I’d highlight the core values of the NIH-funded research system as a whole. This seems a good exercise particularly since many of my posts trend toward critique. It strikes me that many of my criticisms of the NIH arise from a failure of the system to live up to the ideals to a sufficient degree. This is a VeryGoodThing, much better than being in the position of criticizing intentional behavior. So I recognize that these strengths are not perfectly realized. It is, however, important that these are the ideals and goals of the system.