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MDPV completely protects against the neurotoxic effects of methamphetamine

You might define neurotoxicity as damage to any part of a neuron, in the case of MDMA it is just damage to the "branches" of the tree, while the trunk (cell body) is untouched. It is true that SERT levels can certainly return to normal with abstinence. SSRIs can increase neurogenesis, how exactly that would impact recovery from MDMA is uncertain, but I think that it would be beneficial as far as staving off depression (exercise would be similar to SSRIs in the sense that it increases neurogenesis). If it causes insomnia I'm not sure I would stay on SSRIs.

This all predicates on MDMA being a serotonin neurotoxin in humans though, which I think is still up in the air, but if you took 1g MDMA every day for years it is likely. Some studies (I'm thinking of the MAPS study) suggest that humans can take MDMA a couple times with zero issues. There could be other factors causing issues in people who have used MDMA in the past besides harm to serotonin nerve terminals, especially if the use occurred within a year.
 
I agree that MDMA can be very harmful, but I'm not sure if people who get long term comedowns from their first pill and such are experiencing those negative effects because of serotonin neurotoxicity. I'm certainly open to the idea that it is because of serotonin nerotoxicity though, but I'm something of a wishful thinker, especially when it comes what you say to people who are experiencing problems after MDMA. I think I wouldn't hesitate to tell someone who hasn't done MDMA before that MDMA is probably damaging the serotonin neurons but I don't think I would say that to someone who has already done MDMA and is having lots of issues (It is very depressing to think that you have permanently damaged your brain).
 
Well yeah because it blocks the releasing effects, eg the effects of meth, also its dose dependent, the doses used in those studys are of such nature that mdpv is ingested in high enough doses to overtake the release, also because of some weird coincidence the affinity of the dri or sris is allways higher then the releasers, oh well a sciencetist wants to proof science yo.

Practically you can combine releasers and reuptake inhibitors, allways combined mpa, ethyl, 3fpm, or desoxy, mdpv and dex, or rit and amo etc.
 
If you think how meth, MDMA or whatever actually physically translates into neurotoxicity down the chain, and you also think about how we assume most of those drugs potentiate a pleasurable experience, you cannot logically have many options to inhibit neurotoxicity without either (a) prematurely terminating the experience or (b) preventing any experience in the first place.

You can bolster free-radical scavenging defences and glucose/ATP input to attenuate B-oxidation, though that probably won't salvage enzyme activity levels. But beyond that? You're essentially having to inhibit or block at some point some aspect of access of NE, DA or 5HT to neurons. It's not a game where you can have your cake and eat it, not for some mythically prolonged hyperexcitable period anyway.
 
Taking antioxidants to prevent oxidative stress induced by stims is a idiot idea as they can turn pro oxidant, so you can easily induce more damage, nonody has any idea what doses of antioxidants to take, that said im pretty confident that most damage induced by stims can easily be prevented by neuroprotective supplements or meds, another example, you can prevent tolerance to strong stims, while potentiating them while also preventing possible excitoxic damager, like with memantine.

With preventing damage i mean in a simular manner as cleaning the house, not bleaching everything and using dettol like microbe freak, with the right supplements you wont induce more damage then exposure to alot of the common polutants do, actually alot less, chronic exposure to bpa and other environmental toxins(no not aspartamae and msg wich are proven perfectly safe, just wanted to ass that inm everyine allways goes on about them while ignoring the real crap) is far worse then using drugs in a safe matter.

hald of the population is of risk of getting cancer, and most drug arent cancirogenous, so if you care about health alot, focus on other things too)
 
I do take your point, but I wouldn't consider a conservative antioxidant intake foolish with acute high-dose stim use. You could also use studied neurotoxic doses of typical antioxidants as a rough guide if this is a major concern.

However you can bolster some endogenous brain defences (eg GSH) using taurine which will not turn pro-oxidant. Though it may be slightly inhibitory on your experience via GABAA. Swings and roundabouts again.

You can alternatively attempt to maintain high ATP production (ALC, glucose/fructose etc), so lessening oxidative load, or perhaps mix both methods.

The idea of meds for potentiation is good in general if it can facilitate an equipotent high with fewer substrate - that would seem to be a win-win. But while memantine may lessen NMDA excitoxicity, for most people it will also antagonise pleasurable effects taken concurrently (or too close within its exceedingly long half-life). However as a recovery tool I can see its utility.

I guess it depends whether you perceive protection to include recovery as opposed to strictly prevention of damage in the first place. And also whether you believe that typical recreational doses really do induce neurotoxicity...
 
But while memantine may lessen NMDA excitoxicity, for most people it will also antagonise pleasurable effects taken concurrently
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Anecdotes proof you wrong entirely, it potentiates the euphoria of most drugs ALOT, even makes a can of beer really euphoric, its been documented for cocaine:
The effects of memantine on the subjective, reinforcing and cardiovascular effects of cocaine in humans.
Collins ED1, Ward AS, McDowell DM, Foltin RW, Fischman MW.
Author information
Abstract
Eight male frequent cocaine smokers participated in a 44- to 47-day inpatient and outpatient study to assess the effects of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, memantine, on cocaine self-administration, subjective effects, and psychomotor performance. Participants were maintained on memantine (0 and 20 mg daily) for 7-10 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition, participants smoked four doses of cocaine base (0, 12, 25 and 50 mg), and were subsequently given five opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher ($5.00). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose was systematically varied. Vital signs were recorded every 2 min, and subjective effects were assessed at baseline and after each cocaine or voucher delivery. In addition, psychomotor performance was assessed before and after each self-administration session. Memantine maintenance was not associated with changes in psychomotor performance or the number of cocaine doses chosen each session. Memantine maintenance was, however, associated with significant increases in some subjective effects of cocaine, including ratings of 'good drug effect', 'high', 'potency', 'quality', and street value. These data suggest that NMDA antagonists may have limited usefulness as treatment medications for cocaine abuse.
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Ive posted alot about memantine years ago, followed their reports, been reading anecdotes, the last years ive mostly been studying stuff more quetly, alot of the knowledge that was around here what me and others contributed got lots, memantine makes GBL, psychedelics, stimulants, empatogens etc extremely euphoric, i remember taking the combo of 2cd and GBL every evening on it, it was like a mindblowing mdma like experience without any downsides, tolerance, comedown or anything at all for the weeks i used, i will dig up old threads fron around differened fora to proof to ya.

but I wouldn't consider a conservative antioxidant intake foolish with acute high-dose stim use.
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It depends how much damage you would consider that stim dose to cause, a conservative dose would most certainly pro oxidant as it would be overpowered by the pro oxidants, and if you consider the normal indued damage high then id see that as foolish.

im not talking about neurotoxic doses of antioxidants im taking about anti oxidants becoming pro oxidant, basicly like how your nice neughbour becomes a IS figheter as he didnt have many friends and the bigger is group turned him into a suicide bomber.


personally i wouldnt but i never really never took much neuroprotection with drugs, while i easily took 800mg worth of mdma in tablets twice evenings a week, gbl every evening, 4mec everyday for 2 weeks one time as i ran out of stims etc, i never tought drugs cause that much severe damage as i never really heared of long term damage induced by drug addiction except perhaps anhedonia with ghb addiciton ive reead in a study but there arent that many anecdotes, and underlying disorders triggered by mdma.
 
Nac isnt a normal antioxidant, it increases glutathione it cant turn pro oxidant and has differened protective effect, i was talking about antioxidants, like the ones pretty girls in class talk about, vitamin c, e and X, oh wait last one causes oxidative stress
 
Cotcha Yankinov said:
Reverse possible MDMA induced damage? MDMA has not been shown to damage the cell body, but yes SSRIs may help with axon recovery and increased neurogenesis. Although many people have bad reactions to MDMA without having any real damage to brain cells (there are other things that can account for symptoms that are not related to neurotoxicity).
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Can you provide any links?
 
Free radicals are used as intercellular messengers to communicate localized stressors and induce systemic protective effects. Generally speaking, excessive supplementation of simple antioxidants like vitamin C, E, etc can have a net harmful effect, even in the absence of any dramatic stressors like methamphetamine binges. See: studies correlating high antioxidant doses with increased cancer risk, cardiovascular dysfunction, etc.

Even relatively specialized antioxidants like CoQ10 might not have a significant net effect due to the body's reduced endogenous production.

NAC is realistically perhaps the best "general purpose" antioxidant to supplement since it serves to replenish the liver's glutathione stores--thus essentially enabling the body to keep doing it's own detox work, rather than doing that work for the body.

But overall, antioxidants really aren't the end-all-be-all of reducing oxidative stress. You should instead be focusing on reducing factors which cause that stress, i.e. Reducing simple sugar intake, reducing hyperthermia (acetaminophen before MDMA reduces hyperthermia-associated neurotoxicity, for example), ensuring adequate sleep, and/or taking some of the unusual routes towards reducing glutamatergic toxicity, etc.
 
Thought I'd comment on antioxidants and cancer - is this possibly because of reduction of the strength of respiratory burst from immune cells?
 
Most studies on pro-oxidative effects of E, C, CoQ10, ALA, Melatonin etc are done in vitro. In vivo the effects don't seem to manifest in the expected way, hinting at the complexity of the issue. Context specificity seems to be crucial.

To take one example, consider E and C. E is assumed to be capable of turning pro-oxidative fairly easily, while C is mostly antioxidative except in particular in vitro circumstances. However when you combine the two, as would happen in vivo, you find that C appears to protect E from turning pro-oxidant by acting as a co-antioxidant, thus demonstrating a synergistic effect. See for instance:

http://www.ncbi.nlm.nih.gov/pubmed/10969031

The premise that oxidative stress, among several other factors, plays an important role in atherogenesis implies that the development and progression of atherosclerosis can be inhibited by antioxidants. In this minireview we discuss several mechanisms by which the antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) may protect against atherosclerosis. These mechanisms include inhibition of LDL oxidation and inhibition of leukocyte adhesion to the endothelium and vascular endothelial dysfunction. Overall, ascorbate appears to be more effective than alpha-tocopherol in mitigating these pathophysiological processes, most likely as a result of its abilities to effectively scavenge a wide range of reactive oxygen and nitrogen species and to regenerate alpha-tocopherol, and possibly tetrahydrobiopterin, from its radical species. In contrast, alpha-tocopherol can act either as an antioxidant or a pro-oxidant to inhibit or facilitate, respectively, lipid peroxidation in LDL. However, this pro-oxidant activity of alpha-tocopherol is prevented by ascorbate acting as a coantioxidant. Therefore, an optimum vitamin C intake or body status may help protect against atherosclerosis and its clinical sequelae, whereas vitamin E may only be effective in combination with vitamin C.
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For research on the idea that context is crucial, take a look at:

http://www.ncbi.nlm.nih.gov/pubmed/26236096

Reactive oxygen species not only cause damage but also have a physiological role in the protection against pathogens and in cell signalling. Mitochondrial nutrients, such as coenzyme Q10 and α-lipoic acid, beside their acknowledged antioxidant activities, show interesting features in relation to their redox state and consequent biological activity. In this study, we tested whether oral supplementation with 200 mg/day of coenzyme Q10 alone or in association with 200 mg/die of α-lipoic acid for 15 days on 16 healthy subjects was able to modulate the oxidative status into different compartments (plasma and cells), in basal condition and following an oxidative insult in peripheral blood lymphocytes exposed in vitro to H2O2. Data have shown that tested compounds produced antioxidant and bioenergetic effects improving oxidative status of the lipid compartment and mitochondrial functionality in peripheral blood lymphocytes. Simultaneously, an increased intracellular reactive oxygen species level was observed, although they did not lead to enhanced DNA oxidative damage. Coenzyme Q10 and α-lipoic acid produced beneficial effects also steering intracellular redox poise toward a pro-oxidant environment. In contrast with other antioxidant molecules, pro-oxidant activities of tested mitochondrial nutrients and consequent oxidant mediated signalling, could have important implications in promoting adaptive response to oxidative stress.
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Or also:
http://www.ncbi.nlm.nih.gov/pubmed/25060102

Abstract: Melatonin (N-acetyl-5-methoxytryptamine), an indoleamine produced in many organs including the pineal gland, was initially characterized as a hormone primarily involved in circadian regulation of physiological and neuroendocrine function. Subsequent studies found that melatonin and its metabolic derivatives possess strong free radical scavenging properties. These metabolites are potent antioxidants against both ROS (reactive oxygen species) and RNS (reactive nitrogen species). The mechanisms by which melatonin and its metabolites protect against free radicals and oxidative stress include direct scavenging of radicals and radical products, induction of the expression of antioxidant enzymes, reduction of the activation of pro-oxidant enzymes, and maintenance of mitochondrial homeostasis. In both in vitro and in vivo studies, melatonin has been shown to reduce oxidative damage to lipids, proteins and DNA under a very wide set of conditions where toxic derivatives of oxygen are known to be produced. Although the vast majority of studies proved the antioxidant capacity of melatonin and its derivatives, a few studies using cultured cells found that melatonin promoted the generation of ROS at pharmacological concentrations (lM to mM range) in several tumor and nontumor cells; thus, melatonin functioned as a conditional pro-oxidant. Mechanistically, melatonin may stimulate ROS production through its interaction with calmodulin. Also, melatonin may interact with mitochondrial complex III or mitochondrial transition pore to promote ROS production. Whether melatonin functions as a pro-oxidant under in vivo conditions is not well documented; thus, whether the reported in vitro pro-oxidant actions come into play in live organisms remains to be established.
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As for cancer, most research is suggesting that since cells utilise oxidation to kill malignant cells, excessive antioxidants are logically a bad choice. But in acute circumscribed situations, such as meth binges, antioxidants are more than likely to have utility, as the overwhelming bulk of papers which have studied using them suggest.
 
Well, about antioxidants I stumbled about emoxypine, which is said to raise dopamine levels through an unknown mechanism. This is the only drug I know so far that impressively reduced subjectively felt dopamine depletion from methyl- and isopropylphenidate (with 125mg taken at morning & night and an additional pill with every phenidate dose). I've used only dosages in the therapeutic range so I can't tell about recreative ones but thought it's worth mentioning.

Anybody knows more about the mechanisms of emoxypine? Is it possible that it somehow directly counteracts dopamine oxidation, thus slower DA metabolism (how much of DA gets actually oxidized?), lessened crash and oxidative stress providing a faster and easier recovery time?
 
I find it astounding that MDPV prevent MPTP parkinsonism. MPTP causes parkinsons due to the metabolite MPP+.

This implies that MDPV blocks a toxic metabolite from entering DAT, MPP+ in the case of MPTP.
 
shugenja said:
I find it astounding that MDPV prevent MPTP parkinsonism. MPTP causes parkinsons due to the metabolite MPP+.

This implies that MDPV blocks a toxic metabolite from entering DAT, MPP+ in the case of MPTP.
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Why is this astounding?

This was a well-understood mechanism of action for MPP+ that is also blocked by cocaine and methylphenidate. Transport inhibitors are quite logically and obviously neuroprotective against uptake-dependent toxins.
 
InterestingFACT said:
Why is this astounding?

This was a well-understood mechanism of action for MPP+ that is also blocked by cocaine and methylphenidate. Transport inhibitors are quite logically and obviously neuroprotective against uptake-dependent toxins.
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MDMA should protect against MPTP (MPP+) then also -- it is a DAT inhibitor
 
shugenja said:
MDMA should protect against MPTP (MPP+) then also -- it is a DAT inhibitor
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It isn't a very potent DAT inhibitor, not is it very selective. It isn't clear how much DAT occupation occurs at normal doses of MDMA, but it may not be close to the level seen with cocaine.
 
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