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InvisibleveggieM

Registered: 07/25/04
Posts: 17,504
How ecstasy can kill brain neurons by cutting their power supply
    #7430490 - 09/19/07 10:55 PM (16 years, 4 months ago)

How ecstasy can kill brain neurons by cutting their power supply
September 19, 2007 - Innovations Report

Research by Portuguese scientists reveals how ecstasy can compromise the neurons in the brain by damaging their mitochondria – the structures responsible for energy production in the cell - causing the equivalent to a “power-cut” on the affected neurons.

The work to be published in the Journal of Neuroscience also reveals that a drug used in Parkinson’s disease is capable of prevent this damage. By showing how ecstasy can directly compromise such a crucial cellular process the research might help an eventual resolution of the two decade-long debate over whether or not ecstasy use is dangerous.

MDMA leads to the production and accumulation of serotonin, a feel-good chemical, which is behind the pleasant effects of the drug. But scientists also know that ecstasy leads to excessive, and most probably toxic quantities of serotonin accumulating in the nerve endings. How this affected ecstasy users, however, was until now not known..

But the Portuguese researchers Ema Alves, Teresa Summavielle, Félix Carvalho and colleagues from the University of Porto and the Porto Polytechnic Institute.

It was known that neurons that produce serotonin eliminate its excess by using monoamine oxidase (MAO), a type of enzyme (enzymes are proteins that mediate chemical reactions) that as it destroys serotonin produces hydrogen peroxide (H2O2). And H2O2 can lead to the formation of free radicals – toxic molecules that when in high quantities can damage the cell components, including DNA, by oxidising them in the same reaction that leads iron to rust. What Alves, Summavielle, Carvalho and colleagues also realised is that in serotonin-producing neurons the existing MAO – which is called MAO-B - is found on the membrane of mitochondria, the structures where nutrients are converted into the energy used by the cell.

Alves and colleagues’ hypothesis was that in these neurons MAO-B, while eliminating the excessive serotonin released in response to ecstasy consume, would produced toxic quantities of free radicals on the mitochondrial membrane. This toxic accumulation could, by affecting the cell energy-producing machine, result in neural death as affected neurons would be incapable of performing basic cellular reactions..

In order to test this hypothesis the team of researchers used four groups of adolescent rats: a group was treated with MDMA, another with MDMA and selegiline – a drug known to block MAO-B activity – and the remaining two served as control. The control groups included one set treated with selegiline alone in order to assure that selegiline had no effect beside MAO-B blocking, and another with an innocuous substance. After some time the animals’ brains were removed and the mitochondria of serotonin-producing neurons analysed. Adolescent rats were used since teenager abusers – ecstasy main users –have particularly vulnerable cerebral and hormonal systems in result of not being yet fully mature.

As hypothesised MDMA-treated rats showed serious damage in their mitochondria including the loss of entire pieces of DNA – mitocondrial DNA codes for proteins involved in the energy-producing process –compromising the whole energetic machine.

On the other hand, animals treated with MDMA and selegiline did not have any signs of mitochondrial problems confirming the importance of MAO-B in MDMA-induced damage. Interestingly, it was seen that MDMA also increase the rats’ body temperature– a hallmark effect of ecstasy – but this was not associated with the mitochondrial damage suggesting that ecstasy was toxic at other levels too.

Ecstasy, or 3,4 methylenedioxymethamphetamine appeared in the raves of the 1980s and although much studied in the last two decades its dangerousness continues to be debated due to the lack of conclusive results. The drug seems to be toxic for neurons (at least in non-humans laboratory models) and has been shown to kill animals but then, relatively few people have died from taking it and those that did it was mostly due to the heatstroke induced by the drug causing respiratory failure. Nevertheless, several studies have suggested that long-term ecstasy users seem to present serious memory loss.

Alves, Summavielle, Carvalho and colleagues’ results reveals a mechanism by which ecstasy leads to “power-cuts” in the brain neurons, compromising their activity and survival. Not only that but this effect was seen in the serotonin-produced neurons and serotonin is known to be involved in memory, which is believed can be compromised by the drug. As consequence the researchers are now investigating if those long-time users of the drug with signs of memory loss show alterations in their mitochondria/serotonin-producing neurons.

Teresa Summavielle, one of the researchers says "We hope that this findings can help convince ecstasy' users, mainly adolescents, that ecstasy really affects the way our brain functions.”


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Offlinewireless
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Re: How ecstasy can kill brain neurons by cutting their power supply [Re: veggie]
    #7430545 - 09/19/07 11:09 PM (16 years, 4 months ago)

Quote:

The work to be published in the Journal of Neuroscience also reveals that a drug used in Parkinson’s disease is capable of prevent this damage. By showing how ecstasy can directly compromise such a crucial cellular process the research might help an eventual resolution of the two decade-long debate over whether or not ecstasy use is dangerous.




It has been proven that it does not cause Parkinson's Disease. The man who said that used methamphetamine in his studies instead of MDMA.


Also the Womwan who published this article wrote "CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES"

Do I think this article doesn't have some sort of biased? Obviously it does.

Quote:

Long-term behavioral consequences of the neurotoxicity produced by 3,4-methylenedioxymethamphetamine (MDMA) in the adolescent rat are still mostly unknown. Here, adolescent male rats (postnatal day 45 PND [45]) were exposed to 10 mg/kg of MDMA, intraperitoneally, every 2 h for 6 h. Controls were given 0.9% saline in the same protocol.




So these rats were given large amount of MDMA compared to their body weight consecutively and then the short term results were analyzed 10 days later? Seems really legitimate to me :rolleyes:


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Offlinelearningtofly
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Re: How ecstasy can kill brain neurons by cutting their power supply [Re: wireless]
    #7430574 - 09/19/07 11:18 PM (16 years, 4 months ago)

http://www.erowid.org/chemicals/mdma/mdma_dose.shtml

The study there gave a dose to people 1/10 of the one given to the rat.. according to this study it would give me over 600mg of MDMA....


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OfflineQuake3
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Re: How ecstasy can kill brain neurons by cutting their power supply [Re: wireless]
    #7431512 - 09/20/07 09:23 AM (16 years, 4 months ago)

Quote:

wireless said:
Quote:

The work to be published in the Journal of Neuroscience also reveals that a drug used in Parkinson’s disease is capable of prevent this damage. By showing how ecstasy can directly compromise such a crucial cellular process the research might help an eventual resolution of the two decade-long debate over whether or not ecstasy use is dangerous.




It has been proven that it does not cause Parkinson's Disease. The man who said that used methamphetamine in his studies instead of MDMA.





Yes, Ricaurte was wrong ( http://en.wikipedia.org/wiki/George_Ricaurte ) but you misread what you quoted. The Parkinson's Drug spoken of in this article is selegiline, which has been shown in this study to prevent the damage caused by the (excessive amount of) MDMA.

Maybe one day we'll see a combination of MDMA and something like selegiline approved for recreational usage.


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Offlinepokermush
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Re: How ecstasy can kill brain neurons by cutting their power supply [Re: Quake3]
    #7431700 - 09/20/07 10:46 AM (16 years, 4 months ago)

Anybody know if the same thing occurs with mushrooms? They seem to have a similar effect (seratonin increase), which should produce roughly the same kind of resulting damage. Not dissing the wonderful shroom -- but I'm curious. Maybe it would be worth getting some selegilin as part of preparing for a shroom trip. It seems to have a lot of brain health benefits anyway.


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OfflineDadeMurphy
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Re: How ecstasy can kill brain neurons by cutting their power supply [Re: pokermush]
    #7431961 - 09/20/07 11:57 AM (16 years, 4 months ago)

AFAIK psilocybin has never been implicated in any kind of neurotoxicity. It acts on serotonergic neurons but in a completely different way from MDMA. It does not directly cause the release of excess serotonin into the synapse.

This article is generally way to simplistic in its treatment of the neurochemistry of MDMA. The article says:

"MDMA leads to the production and accumulation of serotonin, a feel-good chemical, which is behind the pleasant effects of the drug. But scientists also know that ecstasy leads to excessive, and most probably toxic quantities of serotonin accumulating in the nerve endings."

But, MDMA has never been recognized as increasing the production of serotonin AFAIK, and serotonin is not merely a "feel-good chemical". The effects experienced by MDMA users are the result of complex interactions with many monoamine transporters and receptors. Also, while there is an accumulation of serotonin in certain synapses after MDMA is administered, that is not the same thing as an "accumulation in the nerve endings"...if anything it probably means that the 'nerve endings' of the presynaptic neurons become depleted of serotonin...
My point is that this article seems to be written by someone who is fundamentally ignorant about MDMA pharmacology and neuroscience in general.

The study that this article is about also seems to have some serious flaws, as others have pointed out, most notably with the dosages used and with generalizing these results to the real ecstasy-using population.

Several recent studies have failed to find significant memory/cognitive deficits or psychological problems in former ecstasy users. Other studies have found only minor functional differences in certain types of cognitive tests. Confounding factors generally abound in these studies, and from what I can tell, the question of whether or not MDMA-induced neurotoxicity occurs in recreational users is still an open one.


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InvisibleRobo
R Series 66Y
Registered: 05/08/07
Posts: 14,861
Re: How ecstasy can kill brain neurons by cutting their power supply [Re: wireless]
    #7432553 - 09/20/07 02:13 PM (16 years, 4 months ago)

Quote:

wireless said:
It has been proven that it does not cause Parkinson's Disease. The man who said that used methamphetamine in his studies instead of MDMA.



That myth also came from something else as well, check it:

Excerpt from "Ecstasy: The Complete Guide"

Parkinson's Disease is a neurological illness that affects one's ability to move fluidly and causes a tremor when a person is sitting still. Its cause is unknown, but it effects are damaged dopamine neurons in a part of the brain know as the substantia nigra. MDMA does not damage dopamine neurons in any part of the brain, and Ecstasy use does not cause Parkinson's Disease. In 1983, intravenous drug users, believing they were purchasing a form of heroin called China White, inadvertently inject MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) into their veins.

Designer meperidine (Demerol) is sold as MPPP (1-methyl-4-phenyl-4-propionpiperidine). Specific conditions are required for the chemical reaction to produce MPPP. In the event of incorrect synthesis, where the pH is too low or temperature too high, a contaminant, MPTP, is formed. MPTP damages dopamine neurons. These intravenous drug users were left a a severe Parkinson's-like syndrome.

Because MPTP and Ecstasy were popular in the media at the same time (summer of 1985), many TV programs ran shows on so-called designer drugs that featured videos of the immobilized MPTP victims as well as segments about Ecstasy. These two stories became forever linked in the minds of many Americans who viewed the programs.


http://www.maps.org/images/eguide-256x394.jpg


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Offlinewireless
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Re: How ecstasy can kill brain neurons by cutting their power supply [Re: Quake3]
    #7433789 - 09/20/07 07:01 PM (16 years, 4 months ago)

Quote:

Quake3 said:
Quote:

wireless said:
Quote:

The work to be published in the Journal of Neuroscience also reveals that a drug used in Parkinson’s disease is capable of prevent this damage. By showing how ecstasy can directly compromise such a crucial cellular process the research might help an eventual resolution of the two decade-long debate over whether or not ecstasy use is dangerous.




It has been proven that it does not cause Parkinson's Disease. The man who said that used methamphetamine in his studies instead of MDMA.





Yes, Ricaurte was wrong ( http://en.wikipedia.org/wiki/George_Ricaurte ) but you misread what you quoted. The Parkinson's Drug spoken of in this article is selegiline, which has been shown in this study to prevent the damage caused by the (excessive amount of) MDMA.

Maybe one day we'll see a combination of MDMA and something like selegiline approved for recreational usage.




I know what it was saying. I am simply stating what I said previously so people do not make false assumptions or don't comprehend it.


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OfflineDivided_Sky
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Registered: 11/02/03
Posts: 3,171
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Re: How ecstasy can kill brain neurons by cutting their power supply [Re: wireless]
    #7433842 - 09/20/07 07:18 PM (16 years, 4 months ago)

Well guys, just another good reason to take lots of antioxidants, 5-htp and not dose excessively. I don't think anyone thus far has ever demostrated that this kind of toxicity happens and normal human doses.

What the study shows is that we now know HOW people that take 8 pills a day for a week straight 6 times a year damage their brains. But it doesn't imply that it is any more likely to happen with responsible use.


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1. "After an hour I wasn't feeling anything so I decided to take another..."
2. "We were feeling pretty good so we decided to smoke a few bowls..."
3. "I had to be real quiet because my parents were asleep upstairs..."


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