Jabberwocky
Frumious Bandersnatch
- Joined
- Nov 3, 1999
- Messages
- 84,998
If you look at all the studies involving rats and MDMA toxicity, you will find that the rats are administered the MDMA via intra peritoneal (IP) injection, or in some cases directly into a vein or the brain.
This obviously results in an extremely (non-representative) high serum level, regardless of allometric scaling.
Studies have shown that the subjective effects of MDMA on humans are directly related to the serum level reached by the dose. Poor metabolizers apparently have greater subjective effects.
We know that researchers have been unable to find any difference in the brains of healthy volunteers given 1.5 mg per kilogram of MDMA, based on PET pre and post ingestion.
The question is, With the only study evaluating a 1.5 mg/kg oral dose in humans showing no neurotoxic effects, how can we believe anything regarding neurotoxicity based on rat studies using 10 or even 20 mg/kg IP (which scales to be equivalent to two to four mg/kg INJECTED for humans) administered MDMA?
Yes, some small studies of long-term users show lower binding affinities for serotonin, and an increased receptor density. But that isn't necessarily bad. To my knowledge, none of the study participants identified as depressed. Although most were poly drug users not just MDMA users.
We do know that oxidative stress seems to be the driver with respect to any type of neurotoxic effects of stimulants. Accordingly, vitamin C, n -acetylcysteine, and other antioxidants have been shown to ameliorate or abolish the neurotoxic effects of methamphetamine and MDMA in rats that were injected with methamphetamine or MDMA. I think it's safe to say that they would be just as effective if not more so with respect to human oral doses.
The data doesn't speak to multiple dosing per night with respect to humans. Multiple dosing with rats increases neurotoxicity, however, if you INJECTED 2 to 4 mg/kg (160-240mg) three or four times in the span of as little as 2 hours or as long as 12 (Yes, they actually did that to rats. 10 to 20 mg/kg three to four times over the course of a few hours. The # of hours varied by study.), you kind of deserve what you get.
Comments, concerns, criticisms?
This obviously results in an extremely (non-representative) high serum level, regardless of allometric scaling.
Studies have shown that the subjective effects of MDMA on humans are directly related to the serum level reached by the dose. Poor metabolizers apparently have greater subjective effects.
We know that researchers have been unable to find any difference in the brains of healthy volunteers given 1.5 mg per kilogram of MDMA, based on PET pre and post ingestion.
Erowid.org: Erowid Reference 1191 : Effects of MDMA on 5-HT uptake sites using PET and [11C]-McN5652 in humans : Vollenweider FX, Gucker P, Schönbächler R, Kamber E, Vollenweider-Scherpenhuyzen MFI, Schubiger G, Hell D
The Index page for the reference article: Vollenweider FX, Gucker P, Schönbächler R, Kamber E, Vollenweider-Scherpenhuyzen MFI, Schubiger G, Hell D Effects of MDMA on 5-HT uptake sites using PET and [11C]-McN5652 in humans Conference of the German Society for Psychiatry, Psychotherapy and...
www.erowid.org
The question is, With the only study evaluating a 1.5 mg/kg oral dose in humans showing no neurotoxic effects, how can we believe anything regarding neurotoxicity based on rat studies using 10 or even 20 mg/kg IP (which scales to be equivalent to two to four mg/kg INJECTED for humans) administered MDMA?
Yes, some small studies of long-term users show lower binding affinities for serotonin, and an increased receptor density. But that isn't necessarily bad. To my knowledge, none of the study participants identified as depressed. Although most were poly drug users not just MDMA users.
We do know that oxidative stress seems to be the driver with respect to any type of neurotoxic effects of stimulants. Accordingly, vitamin C, n -acetylcysteine, and other antioxidants have been shown to ameliorate or abolish the neurotoxic effects of methamphetamine and MDMA in rats that were injected with methamphetamine or MDMA. I think it's safe to say that they would be just as effective if not more so with respect to human oral doses.
The data doesn't speak to multiple dosing per night with respect to humans. Multiple dosing with rats increases neurotoxicity, however, if you INJECTED 2 to 4 mg/kg (160-240mg) three or four times in the span of as little as 2 hours or as long as 12 (Yes, they actually did that to rats. 10 to 20 mg/kg three to four times over the course of a few hours. The # of hours varied by study.), you kind of deserve what you get.
Comments, concerns, criticisms?