MDMA doses in mice.

[Transform]

A lot of studies on MDMA in mice use doses around 10-20mg/kg, when humans usually take 10% of this. Is there a paper which talks about the sensitivity of mice and rats to MDMA, or are we being conned?

http://www.erowid.org/references/refs_view.php?ID=750

This paper seems to suggest mice are much less affected by redosing, but still give no justification for the 25mg/kg i.p. dose given in the first place.


Edit: it looks like the name for this is allometric scaling.

 

[Folley]

They give such large doses, to tell potential damage to the brain.

In a human, one dose of say 150mg is going to cause almost no noticeable damage. When they give large ass doses, damage is obvious and they can see which regions are effected.


It might seem excessive, but if they didnt do it we wouldnt know half of what we do about the drug

 

[atrollappears]

A reason often cited is that the large quantities given are due to rodents' faster metabolization of MDMA compared to humans.

This. Studies often use what's called the "surface area approximation," I think in an effort to account for this, in which doses are corrected by surface area rather than mass. Mice have 10 times the surface area per unit weight, so the doses are 10 times higher in mg/kg, and for rats it's similar to mice but a little smaller.

However, I don't know what the basis for this approximation is and I don't think it's considered very accurate.

Also, Erowid's explanation is what Folley said, so there are multiple reasons it seems.

 

[nuke]

I think lower doses give no or subthreshold neurotoxic effects, at least for mice. When you're doing research and there's 5,000 things that can go wrong at every step, no one wants to complicate things by using a dose that may or may not induce neurotoxicity.

 

[chaos_destroy]

The paper below compares the dosages between humans and rats and suggests that rat and human doses are much closer to each other based on mg/kg. They mentioned another study that showed that rats and humans both discriminate MDMA at 1.5mg/kg in tests. this suggests that 20mg/kg is way overkill though as mentioned they do this so they can get a measurable result but unfortunately we can't know for sure if there is any damage occurring at normal doses based on these studies. Its also important to note that whether or not neurotoxicity vs neuroadaptation is occurring even in these high doses is debatable.

Baumann, M. H., D. Zolkowska, et al. (2009). "Effects of dose and route of administration on pharmacokinetics of (+ or -)-3,4-methylenedioxymethamphetamine in the rat." Drug Metab Dispos 37(11): 2163-2170.

 

[atrollappears]

The paper below compares the dosages between humans and rats and suggests that rat and human doses are much closer to each other based on mg/kg. They mentioned another study that showed that rats and humans both discriminate MDMA at 1.5mg/kg in tests. this suggests that 20mg/kg is way overkill though as mentioned they do this so they can get a measurable result but unfortunately we can't know for sure if there is any damage occurring at normal doses based on these studies. Its also important to note that whether or not neurotoxicity vs neuroadaptation is occurring even in these high doses is debatable.

Baumann, M. H., D. Zolkowska, et al. (2009). "Effects of dose and route of administration on pharmacokinetics of (+ or -)-3,4-methylenedioxymethamphetamine in the rat." Drug Metab Dispos 37(11): 2163-2170.

This is what I suspected... unfortunately it's often better career wise for researchers to fear-monger than to practice good science.

 

[chaos_destroy]

To be fair its not the science thats wrong so much (in most cases) but rather the conclusions they draw from it. Much like man made climate change studies. Dramatic conclusions will always get you more funding. It is a shame that funding is so limited that people have top resort to this in order to keep getting funded.

 

[atrollappears]

To be fair its not the science thats wrong so much (in most cases) but rather the conclusions they draw from it. Much like man made climate change studies. Dramatic conclusions will always get you more funding. It is a shame that funding is so limited that people have top resort to this in order to keep getting funded.

That's what science is, looking at the data and figuring out what it says. Educated professionals aren't there just to blend rat brains

 

[chaos_destroy]

Yeah true I actually thought that after i wrote that. Luckily there do seem to be a lot more good papers on drugs that aren't biased these days which is a nice change. Still a lot of crap though.