thelearner
Bluelighter
- Joined
- Sep 22, 2010
- Messages
- 78
So there's always an ongoing debate about MDMA neurotoxicity and whether it actually exists, but there have been SO MANY that show neurotoxicity (at least in rats, mice, and non-human primates) of pure MDMA that in my opinion 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.
In addition, virtually everyone who uses MDMA repeatedly / regularly eventually reports a "loss of magic" -- that the subjective effects of the experience are there, but qualitatively just not quite right. Based on the knowledge that MDMA is neurotoxic, it makes sense that it's the destruction of the very neurons critical to the perception of the "full" MDMA experience that causes the "loss of magic." If this is true, 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've based these guesses on an incredibly comprehensive research paper that discusses how and why MDMA is neurotoxic:
http://www.mediafire.com/?wh43mqqle92vimq
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. (This is GROSSLY oversimplified -- correct me as needed).
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, in theory, 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 to prevent neurotoxicity -- BE FUCKING CAREFUL AND USE AT YOUR OWN RISK!)
1. Temporarily prevent the breakdown of DA via inhibition of MAO-B using low-dose 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:
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:
In case there are some wondering how to obtain Deprenyl / Prozac without a prescription, well, a Google search will yield dividends. (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?")
Last, but not least, I'd appreciate a review of the above for safety (any suggestions on dosages, etc. especially) so I can plan accordingly for my next big event. Those in SoCal, see you at Monster Massive. Find me at The Glitch Mob set! YEEEEHAW!
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.
In addition, virtually everyone who uses MDMA repeatedly / regularly eventually reports a "loss of magic" -- that the subjective effects of the experience are there, but qualitatively just not quite right. Based on the knowledge that MDMA is neurotoxic, it makes sense that it's the destruction of the very neurons critical to the perception of the "full" MDMA experience that causes the "loss of magic." If this is true, 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've based these guesses on an incredibly comprehensive research paper that discusses how and why MDMA is neurotoxic:
http://www.mediafire.com/?wh43mqqle92vimq
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. (This is GROSSLY oversimplified -- correct me as needed).
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, in theory, 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 to prevent neurotoxicity -- BE FUCKING CAREFUL AND USE AT YOUR OWN RISK!)
1. Temporarily prevent the breakdown of DA via inhibition of MAO-B using low-dose 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
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!
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.
In case there are some wondering how to obtain Deprenyl / Prozac without a prescription, well, a Google search will yield dividends. (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?")
Last, but not least, I'd appreciate a review of the above for safety (any suggestions on dosages, etc. especially) so I can plan accordingly for my next big event. Those in SoCal, see you at Monster Massive. Find me at The Glitch Mob set! YEEEEHAW!
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
8)
that make more difficult to keep the track 
of where you wanna go... dunno
) and that you will find more proper answers in that other room: