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  #1  
Old 28-09-2010, 04:13
LemonMuncher LemonMuncher is offline
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Summary of MDMA neurotoxic effects

The following question is of a scientific, informative nature, and involves no reference to participation if illegal activity. Hence I 'self-incriminate'

Most of my understanding of brain chemistry was self taught using wikipedia. I understand the various neurotransmitters and what they do. I understand the concept of super agonoists, full agonists, silent antagonists, etc. I know of various recepters related to drugs, such as the 5HT2A seretonin receptors, or the NMDAs.

I understand that MDMA gets you high because it is a seretonin reuptake inhibitor. (I think) because the synaptic vessels cant 'reuptake' seretonin, mass amounts of it float around in the synapse, making you happy. It also somehow releases oxytocin to make you love everyone. Whenever I try to read about the neurotoxic effects of MDMA, however, the information is way to complex for me. Its all about oxidization, and free radicals, and axons and whatnot. Can someone give me a decent, lay person summary about why they think seretonin is neurotoxic
  #2  
Old 28-09-2010, 12:44
Dr. Satan Dr. Satan is offline
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Re: Summary of MDMA neurotoxic effects

Action of MDMA on the Serotonergic neurons

MDMA induces a liberation of Serotonin by inverting the systems of transport which allow, usually, an accumulation of Serotonin in the nerve endings and synaptic vesicles. In the normal conditions, the emitted Serotonin can be recycled by the serotonergic endings. To make this task, the endings contain two systems of transport working in series. The one gets the extracellular Serotonin to admit it into the cell and the other one allows the passage of Serotonin in the vesicles where it is stored in big quantities.

MDMA can be transported just like Serotonin by these two systems, what alters seriously the normal Serotonin transfer. Indeed, MDMA tends to replace and to chase away Serotonin staying in the nerve ending and in the synaptic vesicles. So, instead of entering the ending, then the synaptic vesicles, Serotonin tends to follow the inverse way from both cellular compartments.

Action of MDMA on the Dopaminergic neurons

MDMA also acts on the transport of Dopamine in the dopaminergic endings, in a similar way just like with Serotonin. But, the affinity of MDMA for the Dopamine recapture sites is 40 times weaker than for the Serotonin recapture sites.
The second mechanism also acts in the sense of a bigger liberation of Dopamine. It is linked to the fact that serotonergic fibers connect dopaminergic neurons in the brain. In this synapsis, the released Serotonin by MDMA is going to incite the neighboring dopaminergic neuron which begins to release Dopamine in abundance.

MDMA neurotoxicity

Studies showed an important loss of serotonergic endings at a frequent user of MDMA. MDA has a slightly superior toxicity to MDMA. On the other hand, MDEA for example, reduces 5-HT and tryptophan hydroxylase with the same efficiency as MDMA. But these rates go back up very fast when the drug disappears and the long-term degenerations are much lighter. It was calculated that it was needed 4 times more MDEA than MDMA to have comparable reductions of the serotonergic central innervation.

The selective destruction of these serotonergic endings would be due to the toxic substance generated by MDMA and would enter, preferentially, in the serotonergic fibers by the Serotonin recapture system.

Two hypotheses: this could be linked to the neurotoxic metabolite of MDMA produced outside of the brain, or to released neurotransmitters as Dopamine, which would become harmful by their excessive quantity.

Thus, this Dopamine, abnormally raised in the extracellular environment, would affect by a badly defined mechanism serotonergic neurons where its tendency to the auto-oxidation would make it toxic. So, if we compare MDMA, MDA, and MDEA, we can notice that more the compound releases powerfully Dopamine, more this release will destroy serotonergics fibers.

In conclusion:

MDMA provokes a degeneration of the serotonergic fibers, and also the released Dopamine is toxic to Serotonin cells. So we have a double MDMA neurotoxic action. That's why a combination with Amphetamines is strongly disadvised, Amphetamines powerfully release Dopamine.

Hope this can help

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very informative post
  #3  
Old 28-09-2010, 13:16
_Dante_ _Dante_ is offline
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Re: Summary of MDMA neurotoxic effects

Thank you for such a comprehensive reply.

How much damage is this doing though? More specifically, with each use, how much?

Obviously damage increases with use, but a 'frequent' user would be someone who uses how often?

If someone were to use MDMA around once a month for example, to what extent is this damage likely to become an issue?
  #4  
Old 28-09-2010, 13:59
Dr. Satan Dr. Satan is offline
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Re: Summary of MDMA neurotoxic effects

This will also depend on doses and not only on frequency. The damaged neurones keep the possibility of growing again, but with repeated doses in the time, this recovery becomes difficult and even impossible. The rates can come back to their previous level from six months to one year after. This reinnervation does not however seem identical to the normal innervation because for example, the concentration of Serotonin stay weak in the frontal cortex while it becomes superior to the normal value in the hypothalamus.

What questions seriously the fact that a normal serotonergic innervation can be restored if this one was affected, in a significant way, by repeated doses of MDMA.

Swiy should avoid Ecstasy pills (mixed MDMA with Amphetamines or some other chemicals).

Drug is like the good wine... Wine has its drunkards, but also many connoisseurs who open from time to time an excellent bottle and who savor it. MDMA should be used with moderation and for some special occasions. Once a month during years should be far enough to prevent a natural nerve recovery.
  #5  
Old 28-09-2010, 15:13
organic_chemist organic_chemist is offline
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Re: Summary of MDMA neurotoxic effects

Quote:
Originally Posted by _Dante_ View Post
Thank you for such a comprehensive reply.

How much damage is this doing though? More specifically, with each use, how much?

Obviously damage increases with use, but a 'frequent' user would be someone who uses how often?

If someone were to use MDMA around once a month for example, to what extent is this damage likely to become an issue?
There are some excellent animations on YouTube, showing how XTC works.
  #6  
Old 28-09-2010, 20:07
Terrapinzflyer Terrapinzflyer is offline
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Re: Summary of MDMA neurotoxic effects

the neurotoxicity of MDMA is still far from fully understood/agreed upon. Many of the studies purporting to show neurotoxic effects have been questionable- either in the doses/substance used or whether the results can be translated to humans.

There has been a recent study of non-polydrug using "ecstasy" users done by Harvards John Halpern- which is due to be released in the not too distant future which found minimal damage for the most part- but until the study is reviewed it is just that- an unreviewed study.

The turtles aardvark will say that among those he knows that have done pure mdma hundreds of times few if any issues have been reported. Likewise, at the MAPS conference this spring there were many who had been involved in the early days of MDMA research, and reported seeing little to no damage.

Certainly poly-drug use, heavy (ab)use of MDx, and use of impure/adulterated "ecstasy" is likely to increase negative effects.
  #7  
Old 29-09-2010, 01:28
thelearner thelearner is offline
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Re: Summary of MDMA neurotoxic effects

Terrapinzflyer: Some studies have been questioned, but there have been SO MANY that show neurotoxicity (at least in rats, mice, and non-human primates) of pure MDMA that a user is much better off assuming toxicity and taking the appropriate steps to try and mitigate it. We still aren't clear on how the brain recovers from neuron loss, and all the data we have so far seems to point to the fact that while neurons can be recovered, the reinnervation pattern isn't the same as before. I don't know about you, but I like my neurons right where they are.

Also, I'd be willing to bet a small fortune that "loss of magic" that everyone talks about is actually just loss of neurons, and that by focusing on preventing neurotoxicity, we could also potentially allow users to keep the magic forever, even when dosing more frequently! What a wonderful scenario that would be!

LemonMuncher: If you're willing to do some reading and learning, here's an incredibly comprehensive research paper that discusses how and why MDMA is neurotoxic:

wwwDOTmediafireDOTcom/?wh43mqqle92vimq (Change DOT to . -- I don't have enough posts to make links).

Dr. Satan also pretty much covered it above. But I've been meaning to do a post on a proposed methodolgy for PREVENTING neurotoxicity due to MDMA based on info in that article, so here's a brief summary of how we think neurotoxicity happens in lay terms, then I'll talk about means to prevent neurotoxicity.

1. MDMA causes a powerful release of Serotonin (5-HT) and Dopamine (DA) (and norepinephrine and some other stuff, which doesn't appear to play a role in toxicity), leaving 5-HT containing cells "empty."

2. As the body metabolizes MDMA, 5-HT, and DA, toxic metabolites and free radicals are created. In particular, it appears that the metabolism (breakdown) of DA by the enzyme MAO-B is a very important part of neurotoxicity for reasons not well understood.

3. Because serotonin "cells" are "empty," and some of the metabolites and free radicals have an affinity for these areas, they are drawn into these areas and cause damage to mitochondria, DNA, etc. causing cell death, i.e. neurotoxicity.

Other factors:

MDMA raises body temperature. Higher body temp causes a more powerful release of 5-HT and DA and greater production of damaging free radicals.

So, if we can do the following, we can largely prevent neurotoxicity:

(Please note I am NOT an expert, just relaying what I've learned in lay terms. I may get some terms / specifics wrong. This is very much a work in progress and input, suggestions, changes, etc. from those with a stronger background and understanding than I have are certainly welcome. That said, I think we should try to avoid absolutist comments about MAO inhibition / SSRI use and the like -- it is clear there are some risks, and I think all would be best served by an elucidation of those risks in more detail than suggesting it has no place in the prevention of neurotoxicity.)

Those looking to use this for SWIY to prevent neurotoxicity -- BE FUCKING CAREFUL AND USE AT SWIY'S RISK!)

1. Temporarily prevent the breakdown of DA via inhibition of MAO-B low dose using Deprenyl. As mentioned above, breakdown of DA is an important part of neurotoxicity, and prevention of that breakdown through MAO-B inhibition is highly neuroprotective.

(Would 2.5mg to 5mg 2 hours before MDMA consumption be appropriate dose?). This carries some risk as in high enough doses (multiple doses in week leading up to MDMA use or 15mg+), Deprenyl also inhibits the enzyme MAO-A, which is responsible for the breakdown of 5-HT, leading to a high risk of Serotonin Syndrome.

Because DA breakdown is inhibited, there is also an increased risk of speed psychosis and cardiac events, so MDMA doses should probably start much lower and be more moderate to prevent this (start with 1/2 of usual dose and work up SLOWLY, being SURE to avoid "binging" with a 12+ hour session).

In other words, this strategy balances one risk with another -- reduced risk of neurotoxicity with increased risk of speed psychosis / cardiac events. It is, however, my personal OPINION that if used carefully, this could be the cornerstone of preventing neurotoxicity, at least if studies on rats are accurate (they show up to 85% reduction in 5-HT loss using Deprenyl as described!)

WARNING FOR WOMEN: Deprenyl works synergistically with birth control and is roughly 20-30x more potent when taken by someone on birth control. DO NOT use this method if you are on birth control as MAO-A inhibition is almost guaranteed to happen, putting you at incredibly high risk for Serotonin Syndrome.

2. Prevent free radicals created by MDMA metabolism from doing damage using free radical scavengers. This is already well understood and many are doing it by taking antioxidants, though I would guess in amounts that aren't high enough to provide sufficient protection.

Basically, MDMA causes production of reactive molecules with a negative charge. Since molecules want to be neutral (without a charge), they react with other molecules, often destroying them. Sometimes these molecules are part of DNA, cell membranes, mitochondria, etc. and damage to these things causes cell death. However, if we can give these free radicals something to react with instead of, y'know, our BRAINS, then we can prevent a lot of damage.

Free radical scavengers (aka. antioxidants) which have been scientifically proven to reduce neurotoxicity in rats and should should be consumed with MDMA:
  • Sodium Ascorbate (Vitamin C)
  • N-Acetyl-L-Cysteine
  • Alpha-Lipoic-Acid
  • Acetyl-L-Carnitine
I am honestly unsure of dosages / timing on these because I am unfamiliar with how they are metabolized, how long they last, etc. It IS, however, clear that these should be taken in HIGH doses to be effective and reasonably near to consumption of MDMA. Until someone suggests otherwise, I'd suggest taking 2-3x the suggested dose on the bottle 1-2x during the course of the evening to insure that high levels of antioxidants are available to "gobble up" any roving reactive metabolites that want to get in a fight with one's serotonin neurons.

3. Prevent uptake of MDMA & metabolites into neurons. Basically, there are transporters on the surface of neurons that transport (reuptake) 5-HT into the cells. However, when MDMA is taken, it and its toxic metabolites have an affinity for these transporters and are also taken into the cell. If we can prevent this, we can prevent toxicity. It's well documented that taking an SSRI (fluoxetine aka Prozac) with MDMA prevents serotonergic neurotoxicity (but maybe not to other parts of the brain).

Unfortunately, doing so also blunts or entirely prevents the subjective effects of MDMA (aka ROLLIN' BALLZ, BABY!) So, it's not really an option to take it with the MDMA. However, a couple of studies have shown (at least in rats) that taking it 4-6 hours after MDMA prevents or significantly reduces serotonergic neurotoxicity!

So, my suggestion would be to take a low dose Prozac (10-20mg?) at the end of a roll, keeping in mind one should limit the duration of the "roll" to 6h from start to finish (i.e. taking the pill / MDMA to come down). Be aware that taking a Prozac WILL end one's roll, and I am completely unsure of risks / interactions with the low dose Deprenyl suggested above. If someone smarter than me cares to elaborate, it would be appreciated.

4. Reduce or maintain a lower body temperature. This is a tough one. It's been proven that a higher body temperature causes a more powerful release of 5-HT and DA, therefore delivering a stronger "roll." But it also appears to encourage the production of free radicals discussed above and may affect toxicity in other ways not fully understood. It's also pretty damn impractical to prevent body temp increases when you're dancing like a seizure victim in a throbbing mass of 10,000 of your new best friends to the most ecstatic, phenomenal music you've ever heard -- and you're doing it while being rubbed on by some anonymous hottie.

So, attempting to avoid suggestions that would lessen one's experience, I suggest the following:
  • Avoid caffeine (Coke, energy drinks, etc.). Caffeine is known to encourage increases in body temp and increase neurotoxicity of MDMA. Besides, you're rolling -- you shouldn't need it! If you need something besides water (stay hydrated!) to nourish you, I'd suggest uncaffeinated soda, orange juice, etc.
  • Get naked! :P Seriously, wear as little as possible. Seems simple, but the elimination of clothes will help your sweaty ass cool off faster. Ladies, this means a thong and pasties!
  • Have that sexy guy / girl rub ice on you. Besides, it's orgasmic.
That's all folks. Hope that helps!

In case there are some wondering how to obtain Deprenyl / Prozac without a prescription in the US (I can see it now: "Yeah, hey doc, I'm not depressed and I don't have Parkinson's, but love ROLLING MY FUCKING ASS OFF but don't want to damage my brain. Can I get 'script for Deprenyl and Prozac?") well Google is your friend.

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Wonderfully structured poist. Great contribution! Thanks!
  #8  
Old 29-09-2010, 03:31
Priapism9 Priapism9 is offline
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Re: Summary of MDMA neurotoxic effects

Great post! I've said it before and I'll say it again. Have 1 or two Vodka Orange Juices before and just after swiy starts rolling, and the body heat issue will NOT BE A PROBLEM. You will NOT heat up (unnaturally, while standing around doing nothing).

Alcohol regulates body temperature and this provides a protective effect. If you're a dumbass who can't control yourself with alcohol and taking 1 drink means you're going to go too far, and overdo it, then dont take this advice. Those people are probably the same ones who can't text and drive or talk on the phone and drive at the same time either. I can.

If you're a responsible individual then swim absolutely recommends 1-3 alcoholic beverages to regulate body temperature, followed by an evening of moderate and responsible regular hydration with H20 or OJ.

Swim gets so unbelievably hot without 1-3 Vodka Oranges that he can't even enjoy MDMA at all. But with it, - all is well.

-P-
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Old 29-09-2010, 05:43
thelearner thelearner is offline
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Re: Summary of MDMA neurotoxic effects

Quote:
Originally Posted by Priapism9 View Post
Great post! I've said it before and I'll say it again. Have 1 or two Vodka Orange Juices before and just after swiy starts rolling, and the body heat issue will NOT BE A PROBLEM. You will NOT heat up (unnaturally, while standing around doing nothing).

Alcohol regulates body temperature and this provides a protective effect. If you're a dumbass who can't control yourself with alcohol and taking 1 drink means you're going to go too far, and overdo it, then dont take this advice. Those people are probably the same ones who can't text and drive or talk on the phone and drive at the same time either. I can.

If you're a responsible individual then swim absolutely recommends 1-3 alcoholic beverages to regulate body temperature, followed by an evening of moderate and responsible regular hydration with H20 or OJ.

Swim gets so unbelievably hot without 1-3 Vodka Oranges that he can't even enjoy MDMA at all. But with it, - all is well.

-P-
Excellent point -- alcohol reduces body temp. However, if I recall correctly, it also causes production of free radicals of its own and may have a synergistic negative effect when combined with the MDMA. Does anyone have any more information on the potential risk / rewards of this strategy?
  #10  
Old 29-09-2010, 06:19
Terrapinzflyer Terrapinzflyer is offline
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Re: Summary of MDMA neurotoxic effects

Quote:
Originally Posted by thelearner View Post
Terrapinzflyer: Some studies have been questioned, but there have been SO MANY that show neurotoxicity (at least in rats, mice, and non-human primates) of pure MDMA that a user is much better off assuming toxicity and taking the appropriate steps to try and mitigate it.
I would like to point out again that many of these studies are highly questionable. Bear in mind that for 3 decades +/- the only way to get approval to research with schedule I drugs was to do research whose intention was to show the harmful effect of these substances.

And yet in the past few years we are seeing a flood of studies approved in the US, and worldwide, on the therapeutic uses of these same drugs- something the FDA/DEA and related foreign agencies would not be allowing if they were convinced these substances were particularly harmful.

As stated previously another issue is the extrapolating of data from rats etc to humans. One need look no further then the substance discrimination studies performed by David E Nichols team at Perdue and compare these to later human experience reports to realize there is often little to no correlation.

And oddly, for the amount of MDx used worldwide, we do not seem to see reports of widespread neuro-cognitive defects as would be expected. Of course- it is very rare to find heavy MDx users who are not also using other drugs, so drawing conclusions is complicated at best.

And finally- something thats been bugging me for ages- I have been unable to find any documentation of the source of the MDMA used in many of the studies allegedly showing harm. While the MDMA used in the modern therapeutic studies was produced by Stuart Frescas (the Stuart of the song "stuart" by the Dead Milkmen) of David E Nichols team.

Not to say that MDx is not neurotoxic at all, but where does it stand in relation to even more commonly (ab)used substances such as alcohol?


Quote:
Originally Posted by thelearner
Also, I'd be willing to bet a small fortune that "loss of magic" that everyone talks about is actually just loss of neurons, and that by focusing on preventing neurotoxicity, we could also potentially allow users to keep the magic forever, even when dosing more frequently! What a wonderful scenario that would be!
I tend to disagree- but admittedly there is little to no research in this area- its almost all subjective/ancedotal reports. But I think many hope there is a chemical reason to this- as it could then possibly be prevented or reversed.

But from many of the early researchers I have discussed this with, the gut feeling is the opposite. More, that like anything, one becomes bored with it. Whether food, music, sexual experiences, sport, etc- the early period is always the best- when one is discovering new things. But after awhile, it changes- the so called magic tends to disappear.
  #11  
Old 29-09-2010, 06:48
thelearner thelearner is offline
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Re: Summary of MDMA neurotoxic effects

Quote:
Originally Posted by Terrapinzflyer View Post
I would like to point out again that many of these studies are highly questionable. Bear in mind that for 3 decades +/- the only way to get approval to research with schedule I drugs was to do research whose intention was to show the harmful effect of these substances.
Fair enough. I'm open to that perspective entirely and would really like to see articles / data / etc. as to why the studies are suspect, besides the source of funding.

In particular, it seems odd that there would be so much research into how to PREVENT neurotoxicity if motives were purely to show harmful effects.
Quote:
And yet in the past few years we are seeing a flood of studies approved in the US, and worldwide, on the therapeutic uses of these same drugs- something the FDA/DEA and related foreign agencies would not be allowing if they were convinced these substances were particularly harmful.
Fair point.
Quote:
As stated previously another issue is the extrapolating of data from rats etc to humans. One need look no further then the substance discrimination studies performed by David E Nichols team at Perdue and compare these to later human experience reports to realize there is often little to no correlation.
Would love to see these studies!

As far as rats vs. humans (...wow this sentence took a long time to type. Having your roommates blast into your room with one insisting that the other blow him because he won a foosball game, followed by wrestling amongst the two is distracting...) I think it's fair to say it's hard to draw definitive conclusions, but non-human primates show an even higher sensitivity to neurotoxicity (if studies are to be trusted) than rats, leading ME to believe that it's a reasonable assumption.
Quote:
And oddly, for the amount of MDx used worldwide, we do not seem to see reports of widespread neuro-cognitive defects as would be expected. Of course- it is very rare to find heavy MDx users who are not also using other drugs, so drawing conclusions is complicated at best.
Page 238-240 of the study I referenced does a far better job of arguing this than I ever could. Just read that.
Quote:
And finally- something thats been bugging me for ages- I have been unable to find any documentation of the source of the MDMA used in many of the studies allegedly showing harm. While the MDMA used in the modern therapeutic studies was produced by Stuart Frescas (the Stuart of the song "stuart" by the Dead Milkmen) of David E Nichols team.
I'd sure love to know, too.
Quote:
Not to say that MDx is not neurotoxic at all, but where does it stand in relation to even more commonly (ab)used substances such as alcohol?
Again, fair point. I think it's one of the deep frustrations I have with the general state of the "War on Drugs" -- it's arbitrary based on cultivated societal perceptions of what is "safe" and what is not.
Quote:
I tend to disagree- but admittedly there is little to no research in this area- its almost all subjective/ancedotal reports. But I think many hope there is a chemical reason to this- as it could then possibly be prevented or reversed.

But from many of the early researchers I have discussed this with, the gut feeling is the opposite. More, that like anything, one becomes bored with it. Whether food, music, sexual experiences, sport, etc- the early period is always the best- when one is discovering new things. But after awhile, it changes- the so called magic tends to disappear.
Of course novelty is important, but I think it's important to limit comparisons to other psychoactive substances.

In my personal experience, the subjective effects of ALL other substances I've taken have all remained consistent (to this day) with the sole exception of variation in intensity based on dosage. I'm sure many other users would agree this is the case with most, if not all, drugs they've used with the possible exception of the various forms of speed (coke, amph, meth, etc.) which may also be neurotoxic.
  #12  
Old 01-10-2010, 10:38
Dr. Satan Dr. Satan is offline
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Re: Summary of MDMA neurotoxic effects

Already in the 80s, experiences proved that Dopamine is an intermediary in the MDMA toxicity. When we exhaust artificially, by pharmacological methods, the neuronal stocks of Dopamine, MDMA becomes harmless on serotonergic endings. When we make pretreatments by L-Dopa, which strengthen the dopaminergic transmission in the brain, these pretreatments aggravate the serotonergic deficits provoked by MDMA.

The same conclusions from experiences with some 5-HT2 receivers antagonists which prevent the effects of MDMA, at the same time, on the liberation of Dopamine and on the degeneration of serotonergic fibers. So the released Dopamine by MDMA, constitutes one of the most important factors of the serotonergic degeneration.

We can make 3 groups of substances with the capacity to protect serotonergic neurons:

The first group is constituted with serotonergic substances, Serotonin specific recapture inhibitors as Fluoxetine (Prozac) and those which interact with 5-HT2 receivers as Ritanserin and Ketanserin.

The second group combines substances which neutralize oxidizers and those who inhibit monoamine oxidase as b-deprenyl, they prevent the formation of those oxidizers from Dopamine.

The third group is constituted by substances which inhibit the neuronal activity. Glutamate release inhibitors as NMDA (MK801). General anesthetics, Chloral Hydrate (was the first depressant developed for the specific purpose of inducing sleep), and anticonvulsants as Chlormethiazole (a sedative and hypnotic that is widely used in treating and preventing symptoms of acute alcohol withdrawal).
  #13  
Old 05-10-2010, 06:41
chaos69 Gold member chaos69 is offline
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Re: Summary of MDMA neurotoxic effects

There is evidence that the "neurotoxicity" may be neuro adaptation not toxicity. Most studies on MDMA neurotoxicity measure toxicity based on serotonin binding site reduction. A recent study used GFP(fluorescent protein)-labeled serotonin transporter (SERT) to determine level of neurotoxicity and the result was that the SERT was being internalized after exposure to "neurotoxic" doses of MDMA but the axpn itself was still intact. This internalization, in a serotonin binding site experiment, would show up as a reduction in binding sites and hence suggest neurotoxicity. However this GFP localization data suggests it is neuroadaptive not neurotoxic.



Kivell, B., D. Day, et al. (2010). Neuroscience 168(1): 82-95.

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Interesting, though a few choice quotes from the article you refer to would help convey your point
  #14  
Old 05-10-2010, 09:06
WayneHoobler WayneHoobler is offline
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Re: Summary of MDMA neurotoxic effects

Terrapins is absolutely correct.

1. The term "neurotoxicity" is difficult to define. Though no universal definition exists, most definitions are broad enough to encompass both short-term alcohol-induced headaches and the permanent nerve cell loss caused by the drug MPTP.

2. Many hundreds of human subjects have been given MDMA in medical studies sponsored by MAPS over the last several years. There have been careful followups and examinations and there has been zero evidence of any damage to their brains. Furthermore, post-mortem autopsies have been conducted on extremely heavy habitual MDMA users, and all brain/neurosystems examinations were completely normal.

3. All these studies purporting to show damage are questionable... most are funded by forces wanting to vilify any and all drugs and the illegalization of MDMA... they use immense overdoses of MDMA directly injected into the animal, completely unlike typical human usage... one of the primary studies was later retracted due to "accidentally" using methamphetamine instead of MDMA, and the supposed excuses and reason have been found questionable.

For example, here is a quote from the first ref below "studyresponse at maps":

August 2, 2005. Ironically, after NIDA-funded researchers Drs. McCann and Ricaurte claimed that MDMA damaged dopamine neurons and could cause Parkinson's disease, a claim that they later had to retract, new research conducted at Duke University Medical Center has shown that MDMA is the most effective of 60 drugs tested in reversing the symptoms of Parkinson's disease! This research was discussed in an article in News-Medical.Net; note also a brief commentary on this and other related research into MDMA as an anti-Parkinson's disease treatment.


PLEASE SEE:

Go to MAPS . ORG and search for MDMA, and also search for Ricaurte

Ricaurte MDMA Research Controversy
(studyresponse at maps)

"Deconstructing Ecstasy" by Dr. Charles Grob.
(2000_grob_1139_1 [pdf] at maps)

MAPS Response to Ricaurte’s Retraction of Ricaurte et al. 2002
(maps_response_100203 at maps)

Scientists Sharply Criticize Conclusions of New MDMA (Ecstasy) Report
(mdmapressrelease at maps)

MDMA Toxicity and Scientific Integrity
(kleiman9.9.03 at maps)

Does MDMA Cause Brain Damage?
(mdma_neurotoxicity1 at erowid)
  #15  
Old 11-10-2010, 23:45
thelearner thelearner is offline
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Re: Summary of MDMA neurotoxic effects

Have been having similar discussions in another thread. Some thinking that axon loss is what's really happening (like trimming branches from a tree as Nichols et. al describe), and that would make a lot of sense for sure.

Still, whether it's neurotoxicity or neuroadaptation, avoidance of either seems highly desirable. For example, avoiding the internalization of SERT (assuming neuroadaptation is the case, not neurotoxicity) would seem to me to be an extremely important goal. ANY change in brain function, toxic or not, should be avoided, no?

Perhaps we should avoid the use of loaded terms like neurotoxicity and instead focus on "best practices for maintaining the consistent levels of SERT binding" using scientifically proven (at least in rats) techniques such as MAO-B inhibition, antioxidant dosing, etc.

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