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(MDMA) Loss of Magic = Loss of Neurons? (or, How to Prevent MDMA Neurotoxicity)

MeDieViL said:
NMDA antagonists upregulate 5HT1A, i dont have any data on the other serotonine receptors, so its questionable wheter memantine can work against mdma tolerance, it works against amp tolerance because nmda antagonists upregulate D2 and D3.

DXM with MDMA is dangerous, ket is just a good drug, it likely doesnt do anything against tolerance, its too short acting and ive never seen anyone succesfully using ket for amp tolerance or something, only succes reports on DXM and memantine.

St johns worth upregulates several serotonine receptors, but it cant be used with MDMA, NMDA antagonists could have an advantage over that, i'm on 40mg memantine, so far i cant give you any anecdotal experience on mdma tolerance as i havent been hammering it lately, so its theoretical.

Also keep in mind NMDA antaogonists generally block or slow tolerance from building up, but they dont really reverse it, they do tend up to speed up recovery when taking a break.
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Thanks for info. I remembered DXM / MDMA being a dangerous combo but couldn't remember where I saw it and why.

As for Ket, interestingly enough, there are reports in your thread of Ket / amp if I remember correctly. In any case, neither here nor there. Sounds like for long term, Memantine is the right choice.

Back to Piracetam...since it is an NMDA antagonist (sort of?), it's possible that it's preventing the build-up of tolerance. So, in terms of dosing, daily dosing may be appropriate + attack doses? Not clear on the dosing regimen on it for best efficacy potentiating MDMA.

Any data on safety with Prozac and/or Selegiline + MDMA? I know that's a hell of a stew, but if it works to generate a powerful roll with low toxicity and a reasonable safety profile, why not? :)
 
Piracetam is a positive NMDA modulator its kinda the opposite as memantine, altough it doesnt appear to be speed up tolerance to drugs, it has a complex mechanism of action.

Just take some on the day your gonna take MDMA, it potentiates drugs right away, it wont block tolerance tough (i got tolerant on the piracetam mdma combo) it will likely help with neurotoxiticy as its a potent neuroprotectant.

Just go for MDMA + antioxidants, fuck prozac.
 
Its in my thread, bottem of all refs.

The antidepressant effect of ketamine is due to mTOR, riluzole failed to prolong it so the antidepressant effects of ketamine, memantine may be due to a differend mechanism too, probably multiple factors togheter.
 
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MeDieViL said:
Piracetam is a positive NMDA modulator its kinda the opposite as memantine, altough it doesnt appear to be speed up tolerance to drugs, it has a complex mechanism of action.

Just take some on the day your gonna take MDMA, it potentiates drugs right away, it wont block tolerance tough (i got tolerant on the piracetam mdma combo) it will likely help with neurotoxiticy as its a potent neuroprotectant.

Just go for MDMA + antioxidants, fuck prozac.
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Just to add to this, piracetam also increases blood flow to the brain, among other things. Which helps potentate amphetamines and most psychoactive drugs.

So is the MDMA cognitive defects might result of too much glutamate (affects NMDA and AMPA receptors), and that this could be modulated (lessened or leveled) by piracetam?
 
Montecarlonos said:
Just to add to this, piracetam also increases blood flow to the brain, among other things. Which helps potentate amphetamines and most psychoactive drugs.

So is the MDMA cognitive defects might result of too much glutamate (affects NMDA and AMPA receptors), and that this could be modulated (lessened or leveled) by piracetam?
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No, MDMA toxiticy is only caused by a combination of its metabolites, oxidative stress and hyperthermia.
 
MeDieViL said:
No, MDMA toxiticy is only caused by a combination of its metabolites, oxidative stress and hyperthermia.
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I'm not referring to toxicity, but to how MDMA users show a significant cognitive/memory impairment vs control. I'm figuring NMDA might be involved, but I'm not sure how. And how this correlates with piracetam bringing back the magic (if at all).

Regardless, it seems like 'losing the magic' is fairly complex and we don't know what exactly is happening.
 
The cognitive impairment is just directly related to MDMA's toxiticy, eg serotogenic neuron loss, interesting to note the cognitive impairment is mild and still within the normal ranges, indicating toxiticy is mild.

Piracetam just brings back the magic, the same way it boosts other drugs, how exactly i dunno, it boosts gabaergics, psychedelics and stimulants, and not all of those cause cognitive impairment or toxiticy.
 
MeDieViL said:
Yes, memantine wont help with toxiticy (it will initially inhibit amphetamine and MDMA and other drugs, during the "memantine adaptation phase" after that A7 upregulates and all drugs work again (with neurotoxiticy, altough NMDA antagonism reduces some amp toxiticy itself, but most is mediated by oxidative stress).

Memantine is an excellent agent for tolerance tough, read my thread on NMDA antagonists and tolerance:
http://www.bluelight.ru/vb/showthread.php?t=501875
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Are you saying that Memantine is ineffective at preventing neurotoxicity when taken before a roll? That goes against what I've read in other threads. And if so, why does it help with the comedown week so much?
 
Special J said:
Are you saying that Memantine is ineffective at preventing neurotoxicity when taken before a roll? That goes against what I've read in other threads. And if so, why does it help with the comedown week so much?
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Yes, that also goes against what I've read elsewhere, specifically a massive review of the mechanism of neurotoxicity which listed Memantine specifically as a means to reduce neurotoxicity when co-administered in rats -- and it was effective at doing so as well.
Memantine is an excellent agent for tolerance tough, read my thread on NMDA antagonists and tolerance:
http://www.bluelight.ru/vb/showthread.php?t=501875
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Even though we don't have much data on how this agent affects MDMA tolerance, can you shed some light on appropriate dosing regimen to prevent / reduce / reverse tolerance? Daily? With MDMA? More info here would be great.
 
Special J said:
Are you saying that Memantine is ineffective at preventing neurotoxicity when taken before a roll? That goes against what I've read in other threads. And if so, why does it help with the comedown week so much?
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It does prevent neurotoxiticy but thats because it inhibits monoamine release at first due to the A7 antagonism, i cant take any amphetamine the first 5 days after raising my memantine dose as its nearly completely inhibited, some individuals can take it right away without noticing inhibition (as you seem to do with MDMA?) but thats usually not the case.

Why it helps the comedown is probably because NMDA antagonists upregulate or keep some dopamine and serotonine receptors sensitive (regarding serotonine only found a reference for 5HT1A but didnt look into it much).

Comedown has nothing to do with neurotoxiticy.

^^ 40 mg seems to work great for amphetamine tolerance for many people, id say that dose is worth a try.
 
I am not going to name names, but some of the people in this thread have little idea what they are talking about, and should read a lot more scientific journals before posting info on NeuroPsychoPharmacology.

I don't have a spare hour to explain every thing, but quickly from what I have read, Memantine has nothing to do with Prozac, Memantine is the best drug for protecting your brain from MDMA and Amphetamine neurotoxicity, but to get the full effect of the drugs do not take any Memantine for a few weeks before taking the drugs, and take Memantine at the same time, or a few hours after the first dose of MDMA or Amphetamine, for maximum protection. I have tried this many times, and it works. If you take Memantine more than a few hours (or more) before the drugs, you get less effect from them, and I will explain why later when I am on a computer keyboard, and not currently slowly typing on my smart phone.

I probably should not write the following, but I currently have 536 PDF's on Memantine on my computer, and nearly 2000 PDF files on Amphetamine, and 1348 PDF files on MDMA , and I have read most of them.

Lastly Piracetam activates AMPA receptors, not NMDA receptors.

I hoped I have helped a bit.
 
The best available data for a specific action of piracetam in the brain is the paper listed below saying it is an AMPA positive allosteric modulator.

Basically it helps the main excitatory ligand-gated ion channel your brain uses stay open a little longer. Regarding how this could help truly prevent MDMA-induced damage it is hard to say. I am not sure it does in the short term period of using the substance and experiencing its effect. The MDMA experience is probably pretty stressful on the brain no matter what. Piracetam probably won't help serotonin receptor downregulation from happening. It is hard to guess at anything else because I don't believe the toxic MDMA metabolite story.

I think piracetam probably potentiates MDMA (as it does for other drugs) pretty well. Enhanced effects could lead to less dosing, or an easier ability to call it quits at 3 AM instead of redosing for the 4th time as piracetam has been noted by some to be able to take the edge off to certain extents.

I also think piracetam is definitely useful for helping your memory function more properly in days after the drug use, for instance if you take piracetam year round and do MDMA once every 10 days for that year, then the overall effect of piracetam towards preventing memory/speech/thought deficits that some people start to have after this frequent of MDMA use might not be nearly as bad because of counteracting effects by the piracetam.

The same could be said for piracetam and cannabis, or other drugs with negative effects on memory, for example.

Then again maybe piracetam also helps the brain recover faster because the AMPA modulation facilitates repair signals (ranging from serotonin receptor replenishment to the dreaded neural cell death mentioned in some of these posts) to function more readily or stay active longer when the brain really needs it. Again not a prevention of the "toxicity" (if you consider receptor downregulation or excessive neural stimulation that) but a way to help recovery.

But if you guys don't think your brain could replace a few dead neurons, you should read up on neurogenesis and how glia can engulf neurons.

First, the precious piracetam:

J Neurochem. 1992 Apr;58(4):1199-204.
Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures.

Copani A, Genazzani AA, Aleppo G, Casabona G, Canonico PL, Scapagnini U, Nicoletti F.

Institute of Pharmacology, University of Catania School of Medicine, Italy.
Abstract

Micromolar concentrations of piracetam, aniracetam, and oxiracetam enhanced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-stimulated 45Ca2+ influx in primary cultures of cerebellar granule cells. Nootropic drugs increased the efficacy but not the potency of AMPA and their action persisted in the presence of the voltage-sensitive calcium channel blocker nifedipine. Potentiation by oxiracetam was specific for AMPA receptor-mediated signal transduction, as the drug changed neither the stimulation of 45Ca2+ influx by kainate or N-methyl-D-aspartate nor the activation of inositol phospholipid hydrolysis elicited by quisqualate or (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid. Piracetam, aniracetam, and oxiracetam increased the maximal density of the specific binding sites for [3H]AMPA in synaptic membranes from rat cerebral cortex. Taken collectively, these results support the view that nootropic drugs act as positive modulators of AMPA-sensitive glutamate receptors in neurons.
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Dr. Beat said:
I am not going to name names, but some of the people in this thread have little idea what they are talking about, and should read a lot more scientific journals before posting info on NeuroPsychoPharmacology.

I don't have a spare hour to explain every thing, but quickly from what I have read, Memantine has nothing to do with Prozac, Memantine is the best drug for protecting your brain from MDMA and Amphetamine neurotoxicity, but to get the full effect of the drugs do not take any Memantine for a few weeks before taking the drugs, and take Memantine at the same time, or a few hours after the first dose of MDMA or Amphetamine, for maximum protection. I have tried this many times, and it works. If you take Memantine more than a few hours (or more) before the drugs, you get less effect from them, and I will explain why later when I am on a computer keyboard, and not currently slowly typing on my smart phone.

I probably should not write the following, but I currently have 536 PDF's on Memantine on my computer, and nearly 2000 PDF files on Amphetamine, and 1348 PDF files on MDMA , and I have read most of them.

Lastly Piracetam activates AMPA receptors, not NMDA receptors.

I hoped I have helped a bit.
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You cant say it prevents neurotoxiticy because of your subjective experience, memantine does work great against the comedowns because it keeps your sensitive sensitive or limits downregulation, that has nothing to do with toxiticy.

Memantine does prevent neurotoxiticy of MDMA and amphetamine, HOWEVER that only occurs acutely because of the A7 antagonism, monoamine release is also mediated trough the A7 receptors, you can notice this for yourself, if you take memantine acutely with amphetamine it will be nearly completely inhibited, untill after a few days were the 17 receptors upregulate again. Offcourse if monoamine release is inhibited neurotoxiticy will be too.
 
I have experimented with this a few times more, it appears that at doses higher then 40mg memantine, mdma is supressed, i suspect that is due to the combination of glutamate supression induced by MDMA and the NMDA antagonism of memantine.

At 20mg memantine works excellent and the comedown is greatly diminshed, the day after i was taking small bumps of ketamine during the day wich should further upregulate some dopamine and serotonine receptors and felt immiadiatly better after, now (this sunday, took the mdma friday) i feel absolutely energetic like i didnt do any drugs in 2 weeks.

The week before i onlly took MDMA on friday, felt a bit skethced out the next day but the day after felt 100% normal again, like i didnt take any in 2 weeks.
 
Sorry for the bump. But i was reading this topic and was very interested in the fact that ketamine could block downregulation and possibly even neurotoxicity as NMDA antagonists prevent downregulation.
So I want to try this. When should the ketamine be taken, is 8 hours after the cap of MDMA is dropped too late? During wich hours does the tolerance build greatly? I was thinking, take MDMA 5 hours before party ends, then I need 2 hours to get home, then take a small bump (30mg) of ketamine + vitamins. Will a single dose help or not? Maybe I would follow up with another small bump when i wake up.

Also would taking 10-20mg of Prozac after 6 hours (so 4,5 hours roll, 1,5 hours come-up) prevent much neurotoxicty? Or is this too late? Could there be any negative effects. I realise any roll remaining will be killed instantly.
 
Taking Prozac 6h after MDMA is pretty much defeating the purpose, by that point all the serotonin has long since been released

& as for NMDA antagonists for tolerance prevcention, ketamine is incredibly short-lived and won't help if you do it 8h afterwards. Generally what you have to do is have a NMDA antagonist active (usually meantine or something) when you take your amphetamine.
 
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