Ecstasy may damage the brain’s physical defences

androoo

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The drug ecstasy reduces the brain’s defences, reveals a new study of rats, leaving it vulnerable to invasion by viruses and other pathogens.

The researchers behind the study warn of "clinical considerations which may apply to the treatment of people who abuse MDMA". For example, anaesthetics could find it easier to penetrate the brain, "greatly increasing the risk of unwanted sedation". And they say infections could cause permanent damage to brain cells or alter the ability of the brain to function normally.

The brain is protected by a fence of tightly packed cells, called the blood-brain barrier. This prevents all but the smallest molecules from passing through. But the new experiments show that MDMA – the chemical name for ecstasy, or “e” – somehow forces open that barrier, allowing larger molecules access to the brain.

Bryan Yamamoto at Boston University, US, and colleagues gave rats four doses of MDMA over 8 hours. “We were trying to approximate a human dosaging pattern,” says Yamamoto. The scientists also injected a blue dye, made of molecules too large to get into the rats' brains under normal circumstances.

One day later, the researchers found the dye had made its way into parts of the brain, such as the caudate and the hippocampus. Ten weeks later, despite no further doses of MDMA being given, new injections of dye were still passing through the blood brain barrier.

Ten weeks in rats could be considered the equivalent of five to seven years in humans. “It does seem to be a very protracted opening,” says Yamamoto. But, as yet, he is unable to say for sure whether the breach is permanent.

Prior protection
Other new research on MDMA has investigated "binges" of ecstasy-taking in rats. Scientists found that rats exposed to many single doses of ecstasy as adolescents are protected from much of the harm caused by e-binges as adults.

Jerrold Meyer at the University of Massachusetts in Amherst, US, and colleagues gave pre-pubescent rats a dose of ecstasy, then repeated the dose every five days, until young adulthood – a total of six doses.

After a period to allow the rats to clear the drug from their bodies, they received up to four times the previous dose spread only over a few hours. The researchers monitored such things as body temperature, body weight and behaviour. A week later, their brains were studied for signs of neurotoxicity.

Typically after a big ecstasy binge, animals suffer hyperthermia, fatigue and lethargy and sustain damage to serotonin axons – the long fibres extending from serotonin-containing neurons. All these features were observed in control rats.

But the rats that had been pre-exposed to the drug were spared these symptoms, including damage to their serotonin system. “Exposure does have this powerful effect to protect animals,” says Meyer.

Therapeutic use
Whether any prior exposure, or only exposure during adolescence, can protect humans this way is not yet clear. “My hunch is that it might be specific to the adolescent period,” Mayer says.

But the mechanism remains a mystery. Among the possibilities is that the pre-exposed animals may be metabolising the drug more quickly, he says, or they may be ratcheting up antioxidant activity in their bodies, or they may be modifying their serotonin receptors.

Not all research on MDMA is into its negative effects. Stephanie Linley at Florida Atlantic University in Port St Lucie points out that the drug is now being investigated for clinical use in diseases as wide-ranging as schizophrenia, post-traumatic stress disorder and terminal cancer.

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Ecstasy may damage the brain’s physical defences
16:53 14 November 2005
NewScientist.com news service
Alison Motluk

http://www.newscientist.com/article.ns?id=dn8314
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Weblinks
Bryan Yamamoto, Boston University
http://www.bumc.bu.edu/Dept/Content.aspx?DepartmentID=65&PageID=7779
Jerrold Meyer, University of Massachusetts
http://www.umass.edu/neuro/faculty/files/meyer.html
MDMA, US National Institute on Drug Abuse
http://www.nida.nih.gov/Infofacts/ecstasy.html
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The drug ecstasy reduces the brain’s defences, reveals a new study of rats, leaving it vulnerable to invasion by viruses and other pathogens.

Increased diffusion of a dye doesn't necessarily mean viruses (which are much, much larger) would be able to get in.

I can't find any such research document that has been published yet; this may be yet another example of a researcher trying to get press attention before having to face peer review.

“We were trying to approximate a human dosaging pattern,” says Yamamoto.

If only we had a way to find out what that dosing pattern was. :-)

Ten weeks later, despite no further doses of MDMA being given, new injections of dye were still passing through the blood brain barrier.

There are several possible explanations. One is the increased expression or activity of some sort of transport system letting the dye in (not damage.) Another is damage to the lining of the brain's blood vessels. If the latter, the obvious question is 'how?' Overheating? Some direct toxic effect on endothelial cells?

Without more information it's hard to determine the significance of these findings.

Ten weeks in rats could be considered the equivalent of five to seven years in humans.

Unlikely. Rats have faster metabolisms...but not that much faster. He seems to simply be thinking of it in terms of 'rat years', ie. if the human lives 80 years and the rats lives for 2 years, then 1 rat week = 40 human weeks. But biology just isn't that simple. :-)

But the rats that had been pre-exposed to the drug were spared these symptoms, including damage to their serotonin system. “Exposure does have this powerful effect to protect animals,” says Meyer.

I can't find a specific article to go with this either. Perhaps I'm just going insane. Anyway, that drug tolerance confers resistance to overdose is not in of itself news, but the line of investigation may uncover interesting new mechanisms behind it.
 
androoo said:
For example, anaesthetics could find it easier to penetrate the brain, "greatly increasing the risk of unwanted sedation".

That makes me want to do it more.
 
For example, anaesthetics could find it easier to penetrate the brain, "greatly increasing the risk of unwanted sedation".

i find that taking codiene, and other sedative drugs (valium, rohypnol) are generally nullified, requiring a higher dose for sedation, when i'm coming off of MDMA. This esepcially applies to the valium/rohypnol as i have a zero tolerance to it. I can't say i notice a weaker or strong affect in the days after taking MDMA but certainly with the pre and post loading the fatigue and my general mood have been greatly improved.

There is no doubt that MDMA effects your brain chemistry. It however has been proven that these affects are far less dangerous then say alcohol and can be nullified by a regime of anti-oxidantants, and other pre & post dosing.

With the sensible use of a tester, and low dosing testing i know i'll prefer my kids to become loved up then boozed when they choice to experince alternative states of consciousness.
 
What was the control for the dye experiment? Were "normal" rats injected with the dye and monitored over the same time period. If someone could find the paper, that'd be great.
 
That's interesting that it opens up the blood-brain barrier - that could actually have some positive potential uses if it could be controlled...
 
That was what I was thinking. Something along the lines of medicinal compounds getting absorbed into the brain better. A lot of supplements have trouble crossing the blood-brain barrier
 
Sorry, but there's so much 'could' and 'might' type statements in there that I'm inclined to think that it's just another exercise in bollocks. They have come up with one possible mechanism to explain dye penetration into the brain, someone else suggested another. They seem to be looking for the worst interpretation of the results to go along with all the anti-drug propaganda - equally the rat weeks vs human weeks statement - that's without even considering the differences in metabolic function & pharmacology (MPTP is perfectly safe for rats, but causes severe irreversible Parkinsons disease in primates). By their own crap time analogies, they were giving MDMA over 8 hours - that's the equivalent of giving it over 320 hours in humans (that's nearly 2 weeks).

I can't find any such research document that has been published yet; this may be yet another example of a researcher trying to get press attention before having to face peer review.

Press attention AND more funding from governmental anti-drug factions. It does have the stench of the Ricaute MDMA is neurotoxic - fact (oops, sorry it looks like we gave the animals methamphetamine instead). I smell a rat - and not the ones being given doses of MDMA!
 
[The National Institute on Drug Abuse (NIDA), National Institutes of Health, today announced it has awarded 10 grants to study the relationship between chronic stress, repeated stressors, and brain mechanisms that affect drug-use behaviors. The grants total $7.6 million over a period of 5 years.

Bryan K. Yamamoto, Boston University School of Medicine, $1,283,554.00 over 4 years
Chronic Stress and MDMA Neurotoxicity.

http://www.nida.nih.gov/Newsroom/03/NR10-1.html

Dr. Yamamoto has served on numerous NIH study sections and currently is a regular member of a NIDA study section. NIH has funded his research continuously for the past 15 years, and his work on the neurotoxicity of methamphetamine and MDMA has been funded by NIDA for the past 10 years.

http://www.drugabuse.gov/Meetings/MDMA/MDMAAbs3.html
 
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fastandbulbous said:
By their own crap time analogies, they were giving MDMA over 8 hours - that's the equivalent of giving it over 320 hours in humans (that's nearly 2 weeks).
^^ This sums it up for them.
 
^

Um i know loads of peeps who have had those kind of amounts of mdma

come to europe is all i can say big mac
 
^^^ I think what he was saying is that the analogy is wrong in the dose schedule if you relate rat time to human time. That would be 4 doses over 320 hours (13.3 days) which obviously is not the same as 4 doses over 8 hours.

What I was wondering is what is the molecular size/weight of dye compared to a virus? That is the freaky part to me. The increased (possibly) permeability of the BBB.

I have never done e as I grew up in a different era, but I have done other psychedelics (including MDA) and I am wondering if this has ever been investigated before with other drugs?
 
If you have an agenda, you can devise research that will lead to any conclusion you wish, really. It's like what I say about the internet -- it's a fuckin' ouija board, because you can find any sort of "proof" to support your cause. As long as you are speaking with words like "maybe" and "might", you can say pretty much anything you want, however meaningless it might actually be -- although enough stupid people will believe it anyway, which is the point of these things. More fuel for the abstinence movement.
 
^^true but it is interesting none the less. Vaguely reminisent of the LSD will screw up your DNA and you will have deformed kids BS in the 60's and 70's. However, nothing comes without consequences. That I have learned the hard way.
 
edarrin said:
^^^ I think what he was saying is that the analogy is wrong in the dose schedule if you relate rat time to human time. That would be 4 doses over 320 hours (13.3 days) which obviously is not the same as 4 doses over 8 hours. ?

Yes, because i doubt there are many people that would take a dose every 80 hours (3.33 days), 4 times.

And even then, as TheDEA.org said, you can't really compare rat times and human times via ratios because it doesn't always work like that.
 
^
ah now i understand i thought like in total or something]

A dealer friend of mine did tell me about this arab kid who popped pills every day for like a few months.
 
Update: The dose used was reportedly 40 mg/kg over six hours (which is about 20 times what would be a strong dose for a human.)
 
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