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Reversing or Attenuating Post-exposure Amphetamine Neurotoxicity

nuke

Bluelighter
Joined
Nov 7, 2004
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Chronic users of methamphetamine or MDMA often seem to show the following symptoms in my experience with them:
-Increased impulsivity and OCD
-Decreased memory and cognition
-Insomnia that is not treatable with medications including antihistamines, benzodiazepines and their derivatives, and other sedatives
-Hypersexuality
-Positive and negative symptoms of schizophrenia
-Chronic fatigue
-Increased anxiety

Most classes of traditional pharmaceuticals to treat these symptoms aren't of any use (SSRIs/tricyclics/NDRIs). Antipsychotics and benzodiazepines can reduce agitation but don't necessarily give any increase in functionality and often reduce cognition.

Is there any possible treatments for extensive serotonergic/dopaminergic neurotoxicity that may benefit these patients? I'm kind of stumped.
 
Many, many things can protect against such prior to actually inflicting the damage, but once done to actually repair or offer compensatory positive effects without further harm is another thing, though indeed there are means, albeit not simple
 
I know it's very preventable beforehand, however it's too late for most of these people who've been IVing meth or eating MDMA pills everyday for years.
 
yeah, just pointing out the facts though, mostly in light to the post above mine

there are agents that can repair and reverse damage but most are by far not readily accessible by any means

with time and patience a nice array of modestly dosed neuropritectants and related may show benefit, but agents that will provide a fix in a short-term are not again largely available

Some agents that have been discussed in other threads of late though may hold some value such as Tianeptine, Deprenyl, and Sulpiride -- depends on the extent of the damage
 
Hey guys (or gals), layman poking his head around here. I know this is probably dependent upon what you use for protection, but does protection = diminished or partial effects of MDMA or Meth?
 
It should not diminish the effect of the drug -- the neurotoxicity of both drugs is mediated by oxidative stress that can either be reduced with antioxidants or by reducing the elevation in body temperature caused through the serotonergic system. Centrally administered MDMA is not neurotoxic, probably due to the bypassing of thermoregulatory dysfunction. If you use a serotonin antagonist to reduce temperature you may have diminished effectiveness of the drug, though.

I've talked about it a lot before, but you can probably reduce neurotoxicity by the use of powerful antioxidants that cross the BBB like idebenone prior and during the drug experience. Antioxidants should not impact on the drug experience at all.

The use of fluoxetine or other SSRIs to saturate the transporters before administering MDMA and prevent neurotoxicity does have a huge impact on the effectiveness of the drug, and generally it will never be as effective with it as it would without it.
 
There are only a few options for "repairing" MDMA- or methamphetamine-induced damage to dopaminergic and serotonergic neurons, so prevention is the clearly the best option. In both MDMA and meth neurotoxicity, the damage is primarily caused by oxidative stress to vulnerable neuronal populations, with resultant mitochondrial failure. In the case of MDMA, the metabolic products following cleavage of the labile methylene moiety--3,4-dihydroxyamphetamine and 3,4-dihydroxymethamphetamine--can initiate free-radical reactions. In the case of high-dose meth, the source of oxidative damage is likely dopamine itself. With so much dopamine released, some of it is spontaneously oxidized up to the quinone species, which is a mitochondrial poison (i.e. it inhibits some of the critical cytochrome enzymes in the oxidative phosphorylation cascade). Once you piss off a cell's mitochondria enough, they signal pro-apoptotic enzymes in the cell, eventually triggering programmed cell death.

As for "restoration," compounds that induce neurogenesis in cortical and hippocampal neurons might be the only solution (and even then, this is a partial solution, as nothing can magically give one "a brand-new brain"), similar to "restoration" of age-related neurodegeneration. Dopamine D2/D3 receptor agonists, such as 7-OH-DPAT, have been shown to induce neurogenesis and dendritic outgrowth in injured dopaminergic neurons. Ergoloids like hydergine, nicergoline, ergometrine and LSD have neuroprotective and neurogenic effects in cortical neurons. Antidepressants promote the release of BDNF--a critical neurotrophin--in the hippocampus, so they might help too. Finally, AMPA receptor modulators like aniracetam can also promote the secretion of a number of neurotrophins like BDNF, NGF, etc...

The take home message should be: if you want to take MDMA, keep your core temperature as low as possible and anti-oxidize the shit out yourself: take antioxidant compounds like high-dose resveratrol, a little Vitamin A/C/E, some selenium, some magnesium and maybe a micro-dose of (l)-deprenyl or an ergoloid.
 
Try Ketamine? :)

Other candidates of interest: Gabapentin and Hydergine.

Maybe: Tianeptine.

Sorry for the snake-oil reply, but there IS some thought put behind these suggestions.

ps. Ketamine and Gabapentin have helped me tremendously in recovery of most symptoms you list post-amphetamine dependence. I am trying Hydergine at the moment and it seems to have something in common with Gabapentin as well as its own actions.
 
Short of MRI results, I don't know why someone would automatically interpret post-stimulant sequelae (depression, anergia, etc.) as the wake of severe neurotoxicity, rather than a long re-regulatory fallout ...
 
These symptoms are often persistent months to years after cessation. I'm just not sure what else they would represent in light of the current evidence we have from animal and human studies.
 
One presenting with symptoms typically arising from chronic use/abuse of all SM amines might be treated using some of the experimental methods mentioned above, if one elects to treat a condition deemed untreatable with anything other than the usual symptomatic approaches, as is almost always the case...however, the 'condition' itself will rarely be considered to be a 'syndrome' of neurotoxicity from abuse, but will be considered, instead, as someone pointed out, to be post stim. sequelae and will be attributed to the usual belief that stimulant abuse leads to prolonged phys. and psych. impairment lasting from months to years [to paraphrase a thousand 'standard' manuals clinicans go by]. Neurotox. will be mentioined out loud only when chronic abuse leads to onset of psychoses indistinguashable from schizophrenia, and only in that case will all the newer treatments be tried, in the inpatient setting. This is to say, i don't see why there is a distinction between the post stimulant abuse 'prolonged' refractory period and the not yet official post stim abuse syndrome of some sort, since it is impossible to tell the two apart [save from some imaging pointing to drastic neural degeneration among other things] and thus, why we should even try to discern between the two, at this point, if diagnostic criteria do not exist. As a preventative measure, wouldn't the ethical clinical response be to go the way of 'regeneration' by whichever means possible, considering that both conditions are serious impediments to the patient, while also taking the symptom based approach of treatment which does not at all interfere with the former 'experimental' one? No, because usually the patient presenting the post stim. 'withdrawal' is often treated like a junkie who deserves what he gets, if I might be so bold as to make such a declaration.....I realize this is not an ethics argument, so forgive me for straying.

I was just making a point pertaining to the theory which dismisses any sort of complex series of disorders arising from stim. abuse as a rarity, and accepts a ten year episode of psychosocial impairment as a withdrawal symptom.....outrageous.


About reduction of tox. during use of stimulants - it's typically not done by those who are looking to get high, because as a rule, most agents which are believed to reduce damage usually always take away from the desired high, with the exception of the high dose antioxidants someone mentioned. The hardcore users will avoid everything 'protective', and will often experience a diminished high from agents administered which do not actually interact with the stimulant taken, as placebo effect. This is not common knowledge in non psych. clinical circles, unless they happen to have arisen from a generation exposed to the club circuit of the major cities, wherein the pillhead on the floor 5 times a week will be unable to recall his name and address but will never forget what to mix and what not to mix with his e. Neuroprotective to him is anathema. Just like it is to the average clinician.

There are all these nootropics springing up and/or coming back in fourth world countries, like Russia, where brain degeneration and neurotoxicity is more common from daily binge drinking and less glamorous than pretty pill stims substances like industrial agents of all sorts and over the counter bromide preparations which are popularly thought to be safe 'traditional' panaceas for everything.....but these nootropics themselves have abuse potential. I will try to find a text and paraphrase it in translation..regarding the 'nootropics'. It's a big deal in Europe, but is commonly dismissed in the US. What is not dismissed is administration of aricept to the ex pillheads of the club scene by the 'progressive' new york city medical community [all I can vouch for, since I don't know about the other communities]. Ergoloids I understand....but aricept and reminyl, and rivastigmine to non-alzh. patients is just ridiculous.


A.A.M.
 
Simply though if we want to break it down a best guideline approach is:

1- Treat the symptoms responsibly with a process to finding the best meds/substrates to do so; both chronic and acute appraoches
2- Use of some form of neuroprotective and neuroregenerative stack with some emphasis on actually neuronal "anabolic" agents -- such are limited but they exist

Now looking at what has been noted already and here certainly exists a few other 'clever' agents if one really wanted to take a pro-active approach they could certainly see some marked improvement with a little diligence and dedication to a program tailored to their impairment, so it is certainly not without hope or possibility

also they likely have a head start on ALZ, PD, and related so those neuroprotectants certainly will serve a purpose even if to not as great as a degree as desired in the short-term than more than certainly one would think in the long-term to hopefully grab a far better potential to develop those conditions later, to a lesser degree, or perhaps even not at all
 
Riemann Zeta said:
As for "restoration," compounds that induce neurogenesis in cortical and hippocampal neurons might be the only solution (and even then, this is a partial solution, as nothing can magically give one "a brand-new brain"), similar to "restoration" of age-related neurodegeneration.

Is there any evidence that neurogenesis improves cognition or alleviates other symptoms?
 
Is there any evidence that neurogenesis improves cognition or alleviates other symptoms?
No, not really, but then again, I don't think there is definitive, hard evidence that anything improves cognition. Meta-cognition is such a subjective phenomenon--objective cognitive tests are often almost worthless in revealing improvements and different individuals respond to different therapeutics, so most cognition-potentiating drugs never pass double-blind, placebo-controlled studies and end up as 'research chemicals.' Hence, the bottom line is: if want to get in to cognition enhancing drugs, you have to put up with a lot of trial and error to see what works for you. Efficacy might not be extraordinary, but your only other option is doing nothing, so I think that it is worth experimenting.
 
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