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Blocking Neurotoxicity of Methamphetamine

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Advanc3d

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Jul 10, 2007
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Blocking Neurotoxicity of Methamphetamine with L-carnitine & Selenium

METH-induced toxicity is related to an increase in the generation of both reactive oxygen (hydroxyl, superoxide, peroxide) and nitrogen (nitric oxide) species. Peroxynitrite (ONOO(-)), which is a reaction product of either superoxide or nitric oxide, is the most damaging radical. It can be reduced by antioxidants such as selenium, melatonin, and the selective nNOS inhibitor, 7-nitroindazole.
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Pre- and post-treatment of mice with l-carnitine (LC) significantly attenuated the production of 3-NT in the striatum after METH exposure. LC is a mitochondriotropic compound in that it carries long-chain fatty acyl groups into mitochondria for beta-oxidation. It was shown also to play a protective role against various mitochondrial toxins, such as 3-nitropropionic acid. The protective effects of LC against METH-induced toxicity could be related to its prevention of possible metabolic compromise produced by METH and the resulting energy deficits.
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http://www.ncbi.nlm.nih.gov/pubmed/12853314


L-Carnitine (LC) is well known to carry long-chain fatty acyl groups into mitochondria for beta-oxidation. It also plays a protective role in 3-nitropropioinc acid (3-NPA)-induced neurotoxicity as demonstrated in vitro and in vivo. LC has also been utilized in detoxification efforts in fatty acid-related metabolic disorders. In this study we have tested the hypothesis that enhancement of mitochondrial energy metabolism by LC could prevent the generation of peroxynitrite and free radicals produced by METH.
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http://www.ncbi.nlm.nih.gov/pubmed/12105098


so does this mean, pre- and post- loading supplement ALCAR/LC and Selenium can possibly block and or largely decrease neurotoxicity caused by meth?

i saw somewhere else on pubmed that administration of deprenyl also is a very good protective aid and its ability to rescue dying dopamine neurons aswell as the MAOI-B effect causing a slow down on the metabolism of dopamine (metabolism of dopamine causing free radical generation)

also, what dose of selenium and carnitine are we talking about here.

though i myself always consume 300mg Selenium, 1500UI Vitamin E, 2grams Vitamin C before and after meth or mdma
 
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A number of antioxidants have a propensity to turn pro-oxidant, often when introduced into an environment that already expresses oxidative stress.

One must step carefully.

Creatine, citicoline, and nicotine have all shown remarkable protective effects against numerous forms of neurotoxic insult, including dopaminergic neurotoxins like MPP+.
 
Erowid has something on the influence of anti-oxidants on the neurotoxicity of MDMA. Not exactly meth, but since they both release dopamine and serotonine I guess it'll be partly true for meth as well.

Personally, I always load up on time release vitamine C tablets when I take stims stronger than caffeine, coca tea or nicotine.
 
I would guess selegiline again because of its ability to reduce oxygen species production via MAO-B.

Selegiline is a specific MAO-B inhibitor. As MAO-B has been shown to be significantly involved in the metabolism of dopamine in certain regions of the primate brain, selegiline has been proposed for use in the treatment of drug addiction. Selegiline is also metabolized in vivo to l-methamphetamine. Therefore, when given in combination with psychostimulants such as d-methamphetamine, there is the potential for adverse effects. To study this possibility, squirrel monkeys were treated with chronic selegiline and tested with two doses of d-methamphetamine (0.1 and 1.0 mg/kg, i.v.). Following at least 7 days of treatment with once daily 0.3 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were no different than the effects of methamphetamine observed prior to selegiline treatment. However, following at least 10 days of treatment with 1.0 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were significantly reduced. Both methamphetamine and amphetamine were detected in plasma following chronic selegiline treatment. When monkeys were given an acute selegiline injection prior to methamphetamine, reduced cardiovascular effects were also seen. These results indicate that selegiline can be used safely even in combination with methamphetamine, as the cardiovascular effects of the drug combination were no greater than either drug alone, and were actually reduced at the higher selegiline dose.
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http://www.selegiline.com/methamphetamine.html

Also most of the same antioxidants as stated before with MDMA; MDMA and methamphetamine have a similar neurotoxic effect. However you may still run into cardiotoxicity from methamphetamine eg cardiac fibrosis and hypertrophy from excess levels of 5HT.
 
is it true about what i read somewhere about selegiline actually blunting the effect of amphetamine use rather than potentiating it?
is their anyway to protect against cardiotoxicity
 
grue said:
A number of antioxidants have a propensity to turn pro-oxidant, often when introduced into an environment that already expresses oxidative stress.

One must step carefully.

Creatine, citicoline, and nicotine have all shown remarkable protective effects against numerous forms of neurotoxic insult, including dopaminergic neurotoxins like MPP+.
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I was not aware of this. What oxidants are these that can turn pro-oxidant?

When using any free radical inducer I usually take vitamin E.
 
Psychedelics_r_best said:
I was not aware of this. What oxidants are these that can turn pro-oxidant?

When using any free radical inducer I usually take vitamin E.
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Vitamans C and E do. Melatonin on the other hand is a powerful antioxidant that does not.
 
Could you explain the mechanism behind that? I usually dose up on vit C before taking stims =/
 
also note that selegiline is metabolised to d-amphetamine....double edged sword?
 
from what i gathered from sciencedirect.com

Administration of methamphetamine with selenium, vitamin c, vitamin e will hinder production of oxygen radicals from methamphetamine metabolism.

combining Selegiline (deprenyl) with combination above will hinder the metabolism of dopamine. when dopamine metabolism is stopped/slowed down, oxygen radicals forming from dopamine metabolism during meth is also attenuated.

sounds like meth is now made safer
 
well, would antioxidants actually help, or is this speculation from the animal studies? cause IIRC, everything i've read said that they gave mice stupidly large amounts (50g?) of Vitamin C by IV in order to notice any protection, and that they didn't know if any Vitamin C orally would be available for use in antioxidant protection.

also, wouldn't cold environments help? i know that cold helps reduce MDMA neurotoxicity, so maybe the same principle would apply to meth?
 
yasu said:
also note that selegiline is metabolised to d-amphetamine....double edged sword?
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AFAIK, it metabolizes into l-methamphetamine, which isn't particularly active.

Advanc3d said:
is it true about what i read somewhere about selegiline actually blunting the effect of amphetamine use rather than potentiating it?
is their anyway to protect against cardiotoxicity
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In my experience, this is true. It blunts the effects, but also protects against a lot of the neurotoxicity. It even protects you against blood pressure changes, I think. I'm not sure about that one, though.
 
im assuming the current stack would be best to counteract meth neurotoxicity

Pre:
300mcg Selenium + Vitamin B-6
1000 UI Vitamin E
2.5mg Selegiline (deprenyl)

After:
5000mg Vitamin C
1000 UI Vitamin E
300mcg Selenium + Vitamin B-6
2.5mg selegiline (deprenyl) - 24 hours after the last dose..


Vitamin C + E + Selenium every night and morning for 3 days after just to be sure.


i never specificly add Vitamin C before/during a stimulant high because ascorbic acid will lower blood pH and increase urinary excertion of meth/mdma. therefore i post load on vitamin c. also neurotoxicty happens when the peak is over from what i understand so then it would be a good idea to load on vitamin c

The Monkey Mantra said:
AFAIK, it metabolizes into l-methamphetamine, which isn't particularly active.



In my experience, this is true. It blunts the effects, but also protects against a lot of the neurotoxicity. It even protects you against blood pressure changes, I think. I'm not sure about that one, though.
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how did you dose on deprenyl
 
just a side note, i took melatonin last nite after taking much amphetamine and my head feels much better, lol.
 
I know that meth amphetamine is a potent stimulant and Melatonin is a rather weak sedative but did it aid at all in your falling asleep? Could that be the main reason why you feel less monged today?

Also please note that from my understanding R-alpha lipoic acid is a far more effective antioxidant than any of the others mentioned above. Please correct me if I am wrong.

Finnally this is something that no one has been able to answer for me yet. What is the proper schedule for administration of ALA and other antioxidants when using stimulants? Is pre loading, postloading, or both needed. And if multiple post loads prove more effective what is an ideal schedule to administer them?
 
i think the aid of sleep along with the antioxidant quality together helped. my head still "hurts" even if i sleep good, but it didnt this time.

as for ALA i always dose about halfway through my session and when i feel im starting to come down. along with lots of water (needless to say)
 
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