Why Ecstasy Researcher Is Smiling

wired news ^ | 9 12 03 | Kristen Philipkoski

[MrLeRoy]

A manful admission (the first I recall ever seeing on an FR WOD thread).

[MrLeRoy]

Make drugs legal any they will be less concenient to obtain.

He said nothing like that.

[DBrow]

I agree in principal; I am not a researcher (and don't play one on TV), but I have read that the reason researchers inject drugs is so that they know more precisely what the blood levels are, without having to worry about the many factors that can change gut or stomach absorption, which can vary from animal to animal and day to day.

If they report serum, brain, or blood levels in the final and normalize the results to that, then I'd be less inclined to reject the results. I have not read the report itself, anybody got a link?

DMT and Salvinorin-A are ineffective when eaten, and Morpheine Sulphate does not work when insufflated, so you do need to worry about how you deliver.

[Texaggie79]

You mean "professional LEGAL dope dealers"....

[corkoman]

you are correct about the value of injecting a test material - the variability of absorption is a bother. But for a safety study to have external validity its best to match the dosing behaviour of the humans.

Did you mean to insufflated- you CAN snort it but it just runs down the throat and you swallow it and its absorbed in the gut. Not the best way to deliver it as it is heavily cleared by the liver.

[DBrow]

Slightly off topic-

I meant that while heroin HCl is absorbed in the nose, MS is not- like you said, it drips into the stomach and is absorbed there.

If you did a study comparing the effects of H and MS, having your baboons snort the stuff would lead to unexpected results.

[45Auto]

You've pointed out some of the problems with the study mentioned here. The biggest problem is that these monkey studies may or may not reflect the human situation, especially so depending on the route of administration. I assume this study was done by i.v. injection. That alone makes it very difficult to draw any conclusions relative to human use of these drugs which is mainly by oral ingestion.

I wonder how it is that some dufus mislabelled the bottles of these two drugs; that kind of thing can get one's DEA controlled substances license pulled, not to mention a whole lot of raised eyebrows among the peer-reviewers of your published work.

[45Auto]

Here's something done recently (admittedly by NIDA; they may have a vested interest in negative findings)

Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice.

Mann, Hema; Ladenheim, Bruce; Hirata, Hiroshi; Moran, Timothy H.; Cadet, Jean Lud.

Molecular Neuropsychiatry Section, NIDA, Addiction Research Center, IRP, P.O. Box 5180, Baltimore, MD, USA.

Brain Research (1997), 769(2), 340-346.

The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic systems were assessed in the striatum and of the nucleus accumbens in mdr1a wild-type and knockout mice. METH caused significant dose-dependent decreases of dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus accumbens (NAc) of both wild-type and knockout mice. The lowest doses of METH (2.5 mg/kg) caused only small changes in the wild-type, but marked decreases in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused similar changes in both strains of mice. In contrast to METH, MDMA caused greater percentage decreases in DAT in the wild-type mice. For example, the lowest dose (5 mg/kg) caused significant decreases in DAT in the NAc of wild-type but not of mdr1a knockout mice. The highest dose (20 mg/kg) caused similar changes in both the strains. These results suggest that METH and MDMA interact differentially with P-glycoproteins. These observations document, for the first time, a role for these proteins in the entry of METH and MDMA into the brain via the blood-brain barrier, with P-glycoprotein possibly facilitating the entry of MDMA but interfering with that of METH into the brain.

[45Auto]

Here's something quite recent from FDA;again, they have a vested interest in negative findings; however, all this work is subject to further research and might contain pieces of the puzzle.

Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA.

Schmued, Larry C.

Department of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, USA.

Brain Research (2003), 974(1,2), 127-133.

Methylenedioxymethamphetamine (MDMA, Ecstasy) is a powerful releaser of serotonin. Increasing recreational use of this stimulant and hallucinogenic drug has raised concerns about its potential to produce brain damage. The vast majority of previous research studies have focused on the compd.'s ability to deplete serotonin (5-hydroxytryptamine, 5-HT) from axon terminals. Despite extensive research on this 5-HT terminal neurotoxicity', a much less studied aspect of MDMA toxicity involves its ability to actually kill nerve cells. Only two prior studies mention the existence of MDMA-induced neuronal degeneration, as reflected by a limited no. of argyrophylic neurons within the somatosensory cortex, following very high doses of MDMA. The development of Fluoro-Jade B as a simple and reliable marker of neuronal degeneration has allowed us to conduct the first comprehensive localization of MDMA induced neuronal degeneration throughout the entire rat forebrain. In addn. to the previously reported neuronal degeneration within parietal cortex, degenerating neurons were also obsd. in the insular/perirhinal cortex, the ventromedial/ventrolateral thalamus, and the tenia tecta. The extent of neuronal degeneration obsd. generally correlated with the degree of hyperthermia achieved.

[45Auto]

And here's something from Italian workers, possibly more of interest:

Ecstasy during loud noise exposure induces dramatic ultrastructural changes in the heart.

Gesi, Marco; Soldani, Paola; Lenzi, Paola; Ferrucci, Michela; Giusiani, Alberto; Fornai, Francesco; Paparelli, Antonio.

Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.

Pharmacology & Toxicology (Oxford, United Kingdom) (2002), 91(1), 29-33.

The acute toxicity induced by 3,4-methylenedioxymethamphetamine appears as rabdomyolysis involving the myocardium (myocytolysis) and it is often suspected to be responsible for sudden death. In line with this, cardiac symptoms such as tachycardia, hypertension, and arrhythmia are present in persons abusing ecstasy. In most cases, ecstasy is abused in loud noise, which in itself might affect the myocardium. To our knowledge no study has investigated the concomitant exposure to ecstasy and loud noise to evaluate the role of the loud noise in modulating MDMA toxicity. In the present study, we analyzed whether cardiac effects following a typical "binging" pattern of MDMA administration are enhanced by concomitant exposure to loud noise. Our findings did not show any myocardial lesion detectable under light microscopy. In contrast, alterations were visible at the ultrastructural level as mitochondrial changes. In particular, we found a marked enhancement in the no. of altered mitochondria when MDMA was administered during exposure to loud noise.

[45Auto]

The one thing that cannot be discounted and is ofetn dismissed is the close structural similairty of MDMA and N-methylamphetamine. These drugs are both amphetamines and thus share certain pharmacological properties, like actions on NE and DA neurons. The ring substitued amphetamines (like MDA and MDMA) have always seemed to me to be "super speed", as they had all the arousal aspects of amphetamine along with certain other properties. They differ from the "top end" compounds (like DOB), which have more in common with the true hallucinogens, and yet still share certain "low end" qualities with unsubstituted amphetamine and N-methylamphetamine. Clearly cardivascular effects may be mediated by NE, DA and even 5-HT pathways. The other central effects may also share common pathways, but diverge at certain points to create the "signature" of each compound, its own little idiosyncratic nature. The same thing is seen in the substituted tyrptamines, by the way.

[DBrow]

Interesting abstracts. I had heard of the rat dopamine studies; Pro-E people dismiss the findings because, after all, it is rats, not men.

The MDMA-Loud Noise study leaves me with many questions- did they sample human heart tissue after dosing people with E and loud music, or did they have little mice rave around with tiny lightsticks while Simon Posford blares from speakers, then sacrifice them for their stressed hearts?
And what in the world does sound have to do with mitochondria? Does something get released in the brain, that then tweaks M-DNA? Or is it the stressful, speed-induced dancing that damages the mitochondria, assuming they can get the rats to dance? That an amphetamine would kick the cell factories into high gear is, I guess, not surprising.

The ring structure does seem to change the activity in a major way. It would be interesting, should such research become legal, to see what the difference is betwween MDA, MDMA, and Indanyl Amphetamine, as well as the effect of putting an ethyl where the methylene is in MDMA, or S where the O is.

Thank you for the interesting posts, 45Auto, I see I've got to spend some time in the university library again to look this paper up. Fascinating.

[thoughtomator]

What would you say to using LSD therapy to reverse-brainwash our public-schooled youth?

[45Auto]

Do you think that would be a good idea?

[rastus macgill]

I suspect there were no mislabelled bottles.The "study" was a fraud in an attempt to get the "right" results.
Legit pure lab grade MDMA is not a high volume production item and is no doubt closely tracked and handled.I don't believe those who have license to legally manufacture and distribute schedule I substances make these kind of mistakes.

[thoughtomator]

I'm not sure, I was asking your opinion, since you seem knowledgable about the field.

[45Auto]

I don't think any powerful CNS drugs should be given to those under 25 years of age, including Ritalin and Prozac. The brain is still developing in children, maybe even into young adulthood. They have enough problems to sort out before and after puberty. No sense screwing them up even further. No, the way out of public school indoctrination/brainwashing is to work to destroy the teacher's unions.

[DBrow]

"The "study" was a fraud in an attempt to get the "right" results. "

If they were going to "dry-lab" it, there are much less expensive fraud methods than killing research primates.

Peer-reviewed science may work slowly, but it (usually) produces good results. Before you publish, others in your field go over your paper preprint and sometimes ask for clarifying information. They try to see if your paper makes sense. After you publish, the next issue will have a letters column in which any weaknesses are ripped apart, then others try to replicate your results. If they are not reproducible, then your initial research is questioned, and in this case they found a mislabeled bottle. This matched their test results; those concerned could see that the substitution most likely caused the effects that they saw.

Fraud is possible but is usually discovered. These guys made an honest, but very serious mistake, admitted it, and are going to correct it. The peer reviewers perhaps should have questioned such severe toxicity, but in this case they did not. Many papers are submitted in a given field, and not that many are published.

Imagine politicians, Drug Czars, and teachers doing this? Admitting that they made a mistake, taking responsibility for it?

If they started out intending fraud, the fact that the wrong drug was administered probably would never come out. Whoever would fund such a fraudulent study, and be willing to kill lab animals to push their agenda, would just expand the vast conspiracy a bit and cover it up.