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Amphetamine Neurotoxicity Reduction/Prevention


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#31 jlspartz

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Posted 08 March 2011 - 10:04 PM

This is all very interesting.

So, on the hopefully good side:
I take P5P, D3, EGCG, Curcumin, Coq10 semi-regularly. I've taken all of them regularly at one time or another. I take bupropion, picamilon, arginine, zinc, and magnesium more often but not quite every day. I also take zolipidem and piracetam regularly, not quite daily but more often than dextroamphetamine.

On the hopefully not-bad side:
I drink heavily several times per month but more typically in the 1-3 drinks range most days.
I don't pay much attention to my diet, and I eat out often. I don't get much exercise
I also am my own human test subject in experiments I occasionally conduct with research chemicals (entirely legal substances, and after considering the long history of scientific self-experimentation I have no ethical qualms). I do extensive research before beginning any experiments, but it's still obviously a factor in my amphetamine use.

Personally, I don't feel like my current amphetamine use is particularly high or inherently dangerous (excluding the potential for cumulative effects from long-term use). I am definitely concerned about using it, I grew up in the middle of one of the earliest big meth booms. I saw beautiful girls destroy themselves all while bragging about staying up all night reading the bible, cleaning the bathroom, doing homework, making mom so proud... It instilled a very deep mistrust of amphetamines in me. I stayed as far away from them as I could (excluding MDMA) until a few years ago when I decided to entertain my docs allegation that I suffered from ADHD.
Adderall was the first one I tried (after going through every non-amphetamine ADHD drug in the book), I don't remember the starting dose but it was far too low to have any noticeable effect. I believe that I may have a low sensitivity to amphetamines, I'm fairly certain that if I didn't take piracetam and magnesium as often as I do I would need to increase my dose.


You feel better taking Piracetam with the Adderall? I'm on a very low dose of Adderall. I tried all the life style stuff and the supplements for years, and then got on Concerta which was a horrible experience, and now Adderall. I can say that I'm not after any euphoria because the stuff makes me dysphoric when starting out. But, I'm only taking 5-10mg XR. 5mg isn't enough but nudges me a little in the right direction. I'm starting 10mg now. Anyway, before the only thing that helped was Piracetam and Oxiracetam, but I'm a little unsure about taking them with Adderall. Also, is taking calcium with any of that bad? My wife takes calcium and magnesium combined pills. I've tried that with the racetams and with Adderall separately resulting in headaches. I'm wondering whether to try magnesium alone.

Edited by jlspartz, 08 March 2011 - 10:05 PM.

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#32 Delta Gamma

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Posted 09 March 2011 - 02:37 AM


This is all very interesting.

So, on the hopefully good side:
I take P5P, D3, EGCG, Curcumin, Coq10 semi-regularly. I've taken all of them regularly at one time or another. I take bupropion, picamilon, arginine, zinc, and magnesium more often but not quite every day. I also take zolipidem and piracetam regularly, not quite daily but more often than dextroamphetamine.

On the hopefully not-bad side:
I drink heavily several times per month but more typically in the 1-3 drinks range most days.
I don't pay much attention to my diet, and I eat out often. I don't get much exercise
I also am my own human test subject in experiments I occasionally conduct with research chemicals (entirely legal substances, and after considering the long history of scientific self-experimentation I have no ethical qualms). I do extensive research before beginning any experiments, but it's still obviously a factor in my amphetamine use.

Personally, I don't feel like my current amphetamine use is particularly high or inherently dangerous (excluding the potential for cumulative effects from long-term use). I am definitely concerned about using it, I grew up in the middle of one of the earliest big meth booms. I saw beautiful girls destroy themselves all while bragging about staying up all night reading the bible, cleaning the bathroom, doing homework, making mom so proud... It instilled a very deep mistrust of amphetamines in me. I stayed as far away from them as I could (excluding MDMA) until a few years ago when I decided to entertain my docs allegation that I suffered from ADHD.
Adderall was the first one I tried (after going through every non-amphetamine ADHD drug in the book), I don't remember the starting dose but it was far too low to have any noticeable effect. I believe that I may have a low sensitivity to amphetamines, I'm fairly certain that if I didn't take piracetam and magnesium as often as I do I would need to increase my dose.


You feel better taking Piracetam with the Adderall? I'm on a very low dose of Adderall. I tried all the life style stuff and the supplements for years, and then got on Concerta which was a horrible experience, and now Adderall. I can say that I'm not after any euphoria because the stuff makes me dysphoric when starting out. But, I'm only taking 5-10mg XR. 5mg isn't enough but nudges me a little in the right direction. I'm starting 10mg now. Anyway, before the only thing that helped was Piracetam and Oxiracetam, but I'm a little unsure about taking them with Adderall. Also, is taking calcium with any of that bad? My wife takes calcium and magnesium combined pills. I've tried that with the racetams and with Adderall separately resulting in headaches. I'm wondering whether to try magnesium alone.


The whole NMDA antagonist thing is to block the influx of calcium through the channel, supplemented calcium might increase the effectiveness of the dose but it could increase tolerance and royally piss off your mitochondria. But, if combined with magnesium it might even out the effects a little bit seeing as Mg2+ is the body's natural NMDA channel blocker. Piracetam has been shown to increase Ca2+ influx through the NMDA receptor via allosteric modulation.

As far as a modest increase in calcium levels goes I wouldn't worry about it too much, but I want you to know possible implications.

/science rant
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#33 rogerthat

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Posted 09 March 2011 - 04:45 AM

If there happens to be any other Diabetics reading this thread, then I found:

an interesting paper to read, seems that the effectiveness, resulting distribution of dopamine/norepinephrine and hence toxicity will vary quite significantly depending on insulin intake.

Likewise, it may be at least somewhat applicable to non-diabetics (carb intake) as well, not sure (?).

Edited by rogerthat, 09 March 2011 - 04:54 AM.

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#34 Delta Gamma

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Posted 09 March 2011 - 07:22 AM

If there happens to be any other Diabetics reading this thread, then I found:

an interesting paper to read, seems that the effectiveness, resulting distribution of dopamine/norepinephrine and hence toxicity will vary quite significantly depending on insulin intake.

Likewise, it may be at least somewhat applicable to non-diabetics (carb intake) as well, not sure (?).


Sort of explains the cognitive impairment seen in diabetics then, might be some sort of glucose-orexin link seeing as orexigenic neurons are really freaking sensitive to glucose concentrations. Interesting link though, especially seeing as the D2 like receptor family increases glucose metabolism in the cell.

http://www.springerl...0803h17l2u7710/

http://care.diabetes.../24/9/1541.full

I remember my grandmother was a type ii diabetic who managed to get off insulin after a year of hardcore diet and exercise, after she lost 100lbs, and she said she never felt sharper after she did that.
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#35 ultranaut

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Posted 09 March 2011 - 05:25 PM

You feel better taking Piracetam with the Adderall? I'm on a very low dose of Adderall. I tried all the life style stuff and the supplements for years, and then got on Concerta which was a horrible experience, and now Adderall. I can say that I'm not after any euphoria because the stuff makes me dysphoric when starting out. But, I'm only taking 5-10mg XR. 5mg isn't enough but nudges me a little in the right direction. I'm starting 10mg now. Anyway, before the only thing that helped was Piracetam and Oxiracetam, but I'm a little unsure about taking them with Adderall. Also, is taking calcium with any of that bad? My wife takes calcium and magnesium combined pills. I've tried that with the racetams and with Adderall separately resulting in headaches. I'm wondering whether to try magnesium alone.


I've not taken piracetam with adderall, but with dexedrine (adderall minus the l-amp) I find it beneficial. I've read claims that this combo could potentially increase the possibility of excitotoxic damage, but I've never seen any support for these claims.
Magnesium at the end of the day semi-regularly helps as well.
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#36 J. Galt

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Posted 10 March 2011 - 08:01 AM


Thanks for starting this discussion. I take amphetamines regularly, prescribed to me for ADHD. To the person who suggested there are better choices out there: I've tried them all, dextroamphetamine is what works best for me. It's not about the euphoria, if you're chasing euphoria with an amphetamine it will lead you right down a dead end.

I made this thread for people like you who have found only amphetamine to help their AD(H)D, however I still believe that there are too many individuals on what should be a last line medication. If you don't mind me asking, what form/dose do you take?

The anti-oxidant link isn't working for me unfortunately.Is something like L-carnosine (on top of curcumin etc.) theoretically helpful in reducing neurotoxicity?Thanks!


http://www.sciencedi...68&searchtype=a

http://www.sciencedi...7b&searchtype=a

http://www.sciencedi...7e&searchtype=a

These links should work, the third one is the antioxidant one. Unless carnosine and curcumin react with each other or have some downstream interaction I don't see any potential interactions, though I'll have to look more into that one when I'm not writing a very important lab paper =/


How would you know if an antioxidant isn't working? You can't feel neurotoxicity.


This is more educated conjecture than anything else, I'm applying what has worked in several animal models to humans. There are several aspects of mammalian amphetamine neurotoxicity which seem to cross all species, and there are also compounds which preform the same functions (for the most part at least) in humans as they do rats/other test mammals the antioxidant link supports my logic if you would like to read a PhD's take on the matter.

More links for you guys to read over:

http://www.springerl...7762m7vwx57t37/ This is another review that covers some new-ish material as is this one: http://www.springerl...5532876p314283/

A absurdly detailed review on various drugs effects on in vivo/vitro stimulant neurotoxicity:
http://books.google....xidants&f=false

And to end on a lighter note some bluelight discussion:
http://bluelight.ru/...ad.php?t=385315

Edit: Forgot to mention that creatine might be of some use to prevent ATP depletion if dosed for a while before ingestion of amphetamine.
Also, there are some rather unusual AD(H)D treatments out there that have sprung up such as low doses of atypical antipsychotics and this stuff http://en.wikipedia....iki/Guanfacine. I haven't heard too much about them, but there is some development going on in the field of new AD(H)D medications.


Trust me, at high enough doses (and especially in sleep deprivation), one most certainly CAN feel neurotoxicity.
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#37 Delta Gamma

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Posted 10 March 2011 - 11:46 PM

Hey, I've realized all the science direct links I've posted only work if you access them through a university IP address. With that said I've been looking for free sources for these papers, and will post them as I find them.

If you really want to see a specific paper PM me and I'll do what I can.

One of the more interesting facets of amphetamine usage is its effects on stress hormones such as GH and cortisol, which are intimately tied with the HPA axis. I'll start posting more on that when I find some solid studies, as it has more implications for the subjective effects of long term amphetamine.
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#38 J. Galt

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Posted 11 March 2011 - 02:01 AM

I just started taking 1mg-2.5mg lithium orotate with my adderall and dex with FANTASTIC results. Will report in a few weeks once I have a better feel for it.
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#39 Delta Gamma

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Posted 12 March 2011 - 09:23 AM

I just started taking 1mg-2.5mg lithium orotate with my adderall and dex with FANTASTIC results. Will report in a few weeks once I have a better feel for it.


Great to hear man! :)
What kind of improvements have you noticed?
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#40 Delta Gamma

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Posted 13 March 2011 - 04:14 AM

I started doing some more reading on amphetamine's effect on the HPA-axis, thyroid, and adrenals and all I can say is: wow. There is so much information that probably should be put out there for people on amphetamine based treatments.

There is some evidence that amphetamine increases T4 levels in the blood in humans, though there is a study (who's full text I cannot access and therefore critique) that suggests that it does not.

http://www.ncbi.nlm..../pubmed/3141826
http://www.ncbi.nlm..../pubmed/6782925
http://books.google....mine t4&f=false

Interestingly enough cortisol seems to be positively correlated with positive amphetamine response.
http://www.nature.co...l/1301373a.html

Growth hormone and cortisol responses seem to be mediated by noradrenergic mechanism independent of the DA system. GH levels are increased and cortisol levels are decreased in monkeys treated with amphetamine.
http://www.ncbi.nlm....v/pubmed/954645

I need to do more reading on the HPA axis and thyroid hormones before I can post any recommendations =/
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#41 Delta Gamma

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Posted 14 March 2011 - 11:45 AM

Hey guys,

I'm probably going to stop visiting this site so often for a few reasons. I'm finding myself posting on here while I should be hunting down research papers to cite for my studies, and there is a lack of intelligent conversation on here. Not to say that there isn't some scientific endeavors going on, but there are many people just repeating the same unsourced arguments over and over again without looking to anything new. Its just not the same intellectual exchange it was before a few other of the more educated posters left, nothing against you guys without a background in this subject matter, but its just not as stimulating.

I'll still post in this thread now and again because I believe it could do someone some good. If you have any questions just post them in this thread and I'll answer them when I stop by. J. Galt post the results of your inosine experiment as well as lithium experiment as well, I think it would be great if we got some datapoints on them. :)

Anyways, have a good one.
-DG
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#42 medievil

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Posted 18 March 2011 - 01:28 PM

Havent read the thread yet, but your best bet for preventing neurotoxiticy is by using agents that induce several pathways that have a highly protective role with regards to dopaminergic neurons, antioxidants may sound like they do the trick (they are known as the best thing ever for health) wich is good as you can make quite a few good bucks by giving ppl the power to fight the damn bastard oxidants with a product you could sell.

Edited by medievil, 18 March 2011 - 01:28 PM.

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#43 medievil

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Posted 18 March 2011 - 01:40 PM

Stay cool, numerous studies have shown increased damage at higher temperatures (see below study).

Yup, altough sometimes jumping around in clubs can be fun too! but i know thats not your goal.

Antioxidants that can cross the BBB mitochondral support may be the key

They may be, or they may turn into pro oxidants and augment damage.

Asprin has been shown to work in rats though I'm unsure of human relevance

Could be a good option.

Switch to methylphenidate its much less toxic

True but its also trash for many.
Apoptosis inhibitors such as curcumin Comparison of MPTP to AMP, inhibition of MPTP induced apoptosis, protection of several aspects of DA system functioning after treatment with 6HODA, there seems to be several additonal pathways involved in curcumin's case though and I am somewhat unsure of the doses/relevance to humans. Here's a massive M&M thread on curcumin.

Yup, this is the best option!
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#44 medievil

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Posted 18 March 2011 - 01:41 PM

Also, I would like to mention again that there has been NO TESTING IN HUMANS for any of the suggestions I have made or commented on

We have years of testing on ADHD patients tough, no real study's but amphetamine as prescribed VERY widely.
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#45 medievil

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Posted 18 March 2011 - 01:46 PM

My advice is the addition of curcumin and memantine for tolerance, if there is an early sign of tolerance on memantine a small break should be taken.
Nothing more has to be done.
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#46 Delta Gamma

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Posted 21 March 2011 - 03:16 AM

Revised Recommendations:
- ~250mg elemental magnesium at bed
- ~1-5mg sublingual melatonin 3 hours before bed
- Stay hydrated, preferably with high quality fruit juices (such as 100% blueberry)
- Eat a balanced diet rich in dark fruits and vegetables.
- Avoid overheating, and when working out stay hydrated
- Curcumin at a self titrated dose, I have added this due to its multiple relevant mechanisms.
- Coenzyme Q10 at 100mg/day in a softgel or oil based formulation (preferably taken with food)
- Avoid sleep deprivation
- A good multivitamin, or at the very least vitamins A,C,E, and D as well as selenium at a significant portion of the RDA value.
- Keep your dose as low as possible.

I believe that this is a good general outline for someone interested in probable harm reduction, though once again I am not a MD and there has been no human testing.

Curcumin from a amphetamine harm reduction perspective has a amazing number of highly relevant actions not limited to: MAOI, iron chelator, antioxidant, apoptosis inhibitor, and stimulator of several trophic factors. Granted, there has not been a study directly on amphetamine use and curcumin in humans, though it has shown some activity in in vitro Parkinson's models.

http://neurotalk.psy...hread66912.html
http://www.ncbi.nlm....pubmed/17184173
http://ihealthbullet...ine-parkinsons/
http://www.mindandmu...41876-curcumin/
http://www.ncbi.nlm....pubmed/19879924
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#47 Delta Gamma

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Posted 27 March 2011 - 08:39 PM

I've been doing some more reading on PQQ and so far it seems to be a very promising compound I'm very tempted to recommend it, so good thing J. Galt brought it up. The only reason I can't give it a solid recommendation yet is that I haven't had time to review possible interactions. With that said, I must add that curcumin does inhibit several p450 enzymes, so for those on very dose sensitive drugs such as anticoagulants it would be wise to ask a pharmacist if you are unsure how to look for interactions yourself.

As far as inosine goes, its virtually nontoxic, and I couldn't find any sort of information on drug interactions, but I'm waiting for a review to be posted. There are also some pharmaceutical or semi-synthetic antioxidants/ neuroprotectants that may be worth mentioning, but they need more research to be done before I feel they should be brought up.

My research on amphetamine's actions on the HPA axis... shits complicated, but when I can sum it up in a simple and relatively straightforward way I will.

-DG
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#48 jadamgo

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Posted 31 March 2011 - 04:19 AM

I'm afraid to name this thing out loud because I'm worried that insufficiently informed people will combine it with AMP in a really stupid way and die/get fucked up... but if you can figure out what I'm talking about, I bet you know how bad it would be to fool around with this combination without being extremely cautious and well-informed about how to do it.

You know that one enzyme that turns dopamine into DOPAC and hydrogen peroxide and ammonia? And you know how DOPAC can react with hydrogen peroxide to form some pretty toxic things? And you know how that enzyme can get inhibited?

What about that one nootropic/antidepressant/antiparkinsonian that people use, which inhibits that enzyme, that some of the studies (which I won't directly post because they name it, but trust me, they're easy to find with minimal effort) say directly protects against dopaminergic AMP-related neurotoxicity in primates and other mammals?

I mean, there are people out there who combine this stuff with AMP. A few of them even do so judiciously, reaching a steady state of enzyme inhibition first and then beginning with a very low dose of AMP titrating it up to desired strength of effect. (In case you're wondering... no, I don't use this combination, because I don't use AMP. It works great for my ADHD, but so does MPH. And unlike AMP, MPH doesn't give me an unpleasant multi-day withdrawal. MPH just causes a mildly euphoric 2-3 hour rebound effect upon wearing off.)

The studies say this combination works well... but people tend to feel very negatively about it. They sometimes even subject those studies to much harsher criticism than the studies THEY cite, presumably because the idea of using this combination is quite uncomfortable.

That's totally understandable -- I feel nervous about this combination, for obvious reasons. But if we're going to be objective here, and make only those claims which are empirically supported, preferably by studies in primates, what would you say about that combination?

Edited by jadamgo, 31 March 2011 - 04:31 AM.

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#49 Delta Gamma

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Posted 31 March 2011 - 05:28 AM

I'm afraid to name this thing out loud because I'm worried that insufficiently informed people will combine it with AMP in a really stupid way and die/get fucked up... but if you can figure out what I'm talking about, I bet you know how bad it would be to fool around with this combination without being extremely cautious and well-informed about how to do it.

You know that one enzyme that turns dopamine into DOPAC and hydrogen peroxide and ammonia? And you know how DOPAC can react with hydrogen peroxide to form some pretty toxic things? And you know how that enzyme can get inhibited?

What about that one nootropic/antidepressant/antiparkinsonian that people use, which inhibits that enzyme, that some of the studies (which I won't directly post because they name it, but trust me, they're easy to find with minimal effort) say directly protects against dopaminergic AMP-related neurotoxicity in primates and other mammals?

I mean, there are people out there who combine this stuff with AMP. A few of them even do so judiciously, reaching a steady state of enzyme inhibition first and then beginning with a very low dose of AMP titrating it up to desired strength of effect. (In case you're wondering... no, I don't use this combination, because I don't use AMP. It works great for my ADHD, but so does MPH. And unlike AMP, MPH doesn't give me an unpleasant multi-day withdrawal. MPH just causes a mildly euphoric 2-3 hour rebound effect upon wearing off.)

The studies say this combination works well... but people tend to feel very negatively about it. They sometimes even subject those studies to much harsher criticism than the studies THEY cite, presumably because the idea of using this combination is quite uncomfortable.

That's totally understandable -- I feel nervous about this combination, for obvious reasons. But if we're going to be objective here, and make only those claims which are empirically supported, preferably by studies in primates, what would you say about that combination?


I too feel very iffy about recommending things that would stop the Cats On My Testicles, it falls under the same category of riskiness as significantly reducing My Alpine Offer to anyone without a solid knowledge of what they're doing. However, from a purely intellectual and hypothetical point of view it is a very solid basis for harm reduction as it would help bypass one of the major free radical generating steps. But, no. Just no for anyone who isn't a neuroscience grad or a stones throw away from a hospital at all times. But, supposing a low affinity, reversible inhibitor were available and some one used it very responsibly while knowing all the warning signs then it might be very beneficial for both dose reduction and avoiding free radicals.

That's also the reason I said curcumin should be used at a self titrated dose, because of its non-selective MAOI effects. Things could get bad fast, especially considering the stuff's absurdly long half life in the brain, if people don't start slow. Granted, its low bioavailability makes me feel a lot better about it.

Now lets hope that these people don't try to find a VMAT2 inducer =/
Of course there's the human to mice and prenatal vs post natal exposure factor to keep in mind. Seems to somewhat explain the fact almost all releasing agents seem to cause issues if used too frequently.


Parkinsons Dis. 2011 Feb 21;2011:124165.
VMAT2-Deficient Mice Display Nigral and Extranigral Pathology and Motor and Nonmotor Symptoms of Parkinson's Disease.

Taylor TN, Caudle WM, Miller GW.

Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA.
Abstract

Dopamine is transported into synaptic vesicles by the vesicular monoamine transporter (VMAT2; SLC18A2). Disruption of dopamine storage has been hypothesized to damage the dopamine neurons that are lost in Parkinson's disease. By disrupting vesicular storage of dopamine and other monoamines, we have created a progressive mouse model of PD that exhibits catecholamine neuron loss in the substantia nigra pars compacta and locus coeruleus and motor and nonmotor symptoms. With a 95% reduction in VMAT2 expression, VMAT2-deficient animals have decreased motor function, progressive deficits in olfactory discrimination, shorter latency to behavioral signs of sleep, delayed gastric emptying, anxiety-like behaviors at younger ages, and a progressive depressive-like phenotype. Pathologically, the VMAT2-deficient mice display progressive neurodegeneration in the substantia nigra (SNpc), locus coeruleus (LC), and dorsal raphe (DR) coupled with α-synuclein accumulation. Taken together, these studies demonstrate that reduced vesicular storage of monoamines and the resulting disruption of the cytosolic environment may play a role in the pathogenesis of parkinsonian symptoms and neurodegeneration. The multisystem nature of the VMAT2-deficient mice may be useful in developing therapeutic strategies that go beyond the dopamine system.

PMID: 21403896 [PubMed - in process]


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#50 medievil

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Posted 31 March 2011 - 12:34 PM

We have to look at the full paper and the mechanisms involved and then look at supplements wich likely counteract those mechanism involved in the neurodegeneration induced by amphetamine.
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#51 Delta Gamma

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Posted 31 March 2011 - 07:33 PM

We have to look at the full paper and the mechanisms involved and then look at supplements wich likely counteract those mechanism involved in the neurodegeneration induced by amphetamine.


Amphetamine releases DA and NE via VMAT2 inhibition, so that's likely not going to happen. The full text is available on pubmed if you want to look over it. It appears that amphetamine's basic mechanism of action is associated with cell death in the long term.

However, we could still address the associated issues of oxidative stress, nutrition, and mitochondrial function associated with amphetamine use to help push back the onset of neurotoxic symptoms.
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#52 jadamgo

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Posted 31 March 2011 - 08:12 PM

Err... my alpine offer makes dopac; cats on my testicles make 3mt.

It appears that amphetamine's basic mechanism of action is associated with cell death in the long term.


I find this statement a bit misleading. It's "mechanism of action" is not one simple thing. Reversing VMAT does not kill the cell directly. It releases lots of dopamine into the axon terminal's cytoplasm, which doesn't get spewed out into the synaptic cleft quickly enough because the DAT can't run backwards very well. And obviously the reversed/inhibited VMAT isn't transporting it back into the vesicles.

Then the dopamine breakdown products and metabolites cause oxidative damage to the cell, which can induce apoptosis if severe enough. Otherwise, the cell repairs itself eventually. Right? Or am I misreading some of the studies?

Anyway, the "mechanism of action" that improves cognition is increased dopamine in the synaptic cleft. Intrasynaptic dopamine does not hurt the cell; if it did, MPH and cocaine would tear neurons up faster than AMP and METH. Of course, MPH actually protects against AMP-induced neurotoxicity.

So it seems quite possible to let AMP do its VMAT reversal thing without necessarily killing the cells. If VMAT reversal automatically spelled the death of neurons, then why would we even speak of harm reduction?

If we can get Chairman Mao to stop producing all that DOPAC and hydrogen peroxide, we've got one way of protecting the cell. (I think it would be terrible to turn off the cats on my testicles; they do far less damage than chairman mao by my understanding.) Yeah, it's hard to manage that, but I don't know that someone necessarily has to be a neuroscience grad to do it. Smart, yes. Educated, yes. Able and willing to notice the red flags indicating problems, yes. But you don't have to be a neuroscience grad to follow instructions.

If we can use MPH to inhibit more DAT and keep the dopamine in the cleft and out of the axon terminal, we've got another way. Another option would be bupropion or something similar, but then again, you'd need a good deal of DAT inhibition.

Maybe some NET inhibition would be good too, to safe those prefrontal neurons which don't have the DAT. But you might not need as much NET inhibition, since NET isn't nearly as good at transporting DA back into the axon terminal. Perhaps AMP itself provides enough NET inhibition; I'm not aware of studies on this. But lots of NE could get the neurons all hot and excited, which wouldn't be too good.

If we can deliver antioxidants into the axonal terminal, we've got yet another way to reduce damage.

Then there's good nutritional and mitochondrial support. I don't know about the evidence on mitochondrial support, so I'll leave that issue to those who know what they're talking about.

A touch of NMDA antagonism could be good too, not only preventing tolerance but also reducing any excitotoxicity that might be present. It probably doesn't play nearly as large a role as dopamine toxicity, but chronic AMP users may want all the help they can get, and NMDA antagonism would help them avoid tolerance too.

What are our other options?
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#53 Delta Gamma

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Posted 31 March 2011 - 08:49 PM

Err... my alpine offer makes dopac; cats on my testicles make 3mt.


Actually you're right, my bad on that one.

As far as VMAT2 inhibition goes, it keeps the cell from properly storing monoamines so you could end up with more dopamine entering the cytosol without being properly packaged. This can allow the the catabolism of DA within the cell which creates reactive species. To the best of my understanding MPH helps prevent neurotoxicity by preventing the DAT from transferring DA into the cell while VMAT2 is inhibited by amphetamine. Inhibited VMAT2 just lets DA and some related compounds pour into the cytoplasm where they can cause oxidative stress.

I say neuroscience grad as a hyperbole, but I did have one friend, who was in honors biochem, put himself into a seizure from combining 5mg amphetamine with a unspecified inhibitor of DA catabolism, but seeing as his grandfather has Parkinson's it could have been just about anyone. My Alpine Offer plan B inhibition could help prevent oxidative stress, but as with stopping the Cats On My Testicles, it could have some negatives in regards to seizures.

Mitochondrial support is pretty much keeping calcium levels down (NMDA antagonism is the most popular way), and keeping oxidative stress down at the mitochondria to prevent it from releasing cytochrome c. Vitamin D has shown some interesting results as far as mitochondrial support goes, and more specifically autophagy for damaged mitochondria which are more likely to signal for apoptosis. Gotta keep those pro-apoptosis mechanisms under control haha.

Here's one study that shows positive results, not sure if it has the explanation though.
http://www.ncbi.nlm....pubmed/17105922

There's also amp's effects on mitochondrial metabolism, but thats a place where it gets really complicated.

Edit: as far as I know NE-genic neurons don't exhibit neurotoxicity in most amphetamine studies, I'd hazard a guess that its due to NET's low DA affinity but I haven't done anything more than a cursory look.

Edited by Delta Gamma, 31 March 2011 - 08:52 PM.

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#54 Delta Gamma

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Posted 31 March 2011 - 08:58 PM

http://www.ncbi.nlm....pubmed/10461904
Some info on DA oxidation and mitochondrial function.
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#55 Delta Gamma

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Posted 01 April 2011 - 08:03 PM

I realized that most of my science direct links don't work, so I'll just post the article information here in order of appearance:

Neuroscience & Biobehavioral Reviews
Volume 27, Issue 8, January 2004, Pages 821-826
Foundations and Innovations in the Neuroscience of Drug Abuse
Amphetamine neurotoxicity: accomplishments and remaining challenges
Una D. McCann and George A. Ricaurte

A fairly solid review

Pharmacology & Therapeutics
Volume 99, Issue 1, July 2003, Pages 45-53
Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress
Jeffrey M. Brown and Bryan K. Yamamoto

Discusses the effects of amp on mitochondrial function and how antioxidants may be of use

Update on Amphetamine Neurotoxicity and Its
Relevance to the Treatment of ADHD
Claire Advokat
Louisiana State University

THE MUST READ REVIEW even for laypeople

Trends in Pharmacological Sciences Volume 25, Issue 3, March 2004, Pages 152-157

This is a review of all the inosine stuff I posted
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#56 Delta Gamma

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Posted 06 April 2011 - 05:54 PM

http://www.ncbi.nlm....pubmed/12384252

Well lithium does induce VMAT2 in rat brains, as for human relevance and non-bipolar dosages I don't know. Still, given the fact that lithium is starting to look like a essential mineral its interesting.
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#57 longevitynow

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Posted 07 April 2011 - 02:42 AM

I'd advise lots of days off, probably best with every other day usage at most. In any case frequent breaks. This will keep your receptors active.
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#58 VoidPointer

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Posted 08 April 2011 - 11:54 PM

I'd advise lots of days off, probably best with every other day usage at most. In any case frequent breaks. This will keep your receptors active.



I my experience this is key.

Also, this article came out today which applies to both AMP and MPH;

http://www.reuters.c...E7371WO20110408


I interpret this as being moderately positive, and it reinforces the fact that stimulants(in particular Methylphenidate) have been extensively studied over decades, and they have a much better idea of their long-term effects than newer meds or experimental noots.
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#59 Delta Gamma

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Posted 16 April 2011 - 08:32 PM

More of a question than anything else, but what supplements do you guy's use currently to help with amphetamine toxicity?
Also, has anyone seen any reports or studies on reversible MAO-B inhibitors and amphetamine? I feel that these could be a much less risky alternative to the much more commonly used irreversible inhibitors.

I've found several herbal compounds exhibiting reversible MAO-B inhibition among other properties aside from curcumin, but I'd like to discuss them more in length with you guys before I start naming off specific compounds and sources.

-DG

Edited by Delta Gamma, 16 April 2011 - 08:44 PM.

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#60 J. Galt

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Posted 20 April 2011 - 03:01 PM

After trying a low-dose lithium regimen with my Adderall XR and IR prescription for over a month, I have to say that it's hands down the strongest neuroprotective supplement I've ever tried (and I've tried most).

Excitotoxicity becomes particularly acute after 24hrs without sleep, especially if you've forgotten to eat. At this point I believe that I can actually feel some aspects of the excitoxicity taking placing, and it is at times like these when I can feel the effects (or lack thereof) of a particular neuroprotectant: the acute sensations of the excitotoxic storm dissipate, as does the associated "brain fog." Previously, I'd felt the strongest neuroprotective responses from:

BioPQQ
GreenSelect Green Tea Phytosome
Meriva Turmeric Phytosome
Astaxanthin
NADH (sublingual)
Sam-e
P5P + Methyl B12 (sublingual)
Fish Oil + Acetyl L-Carnitine (low dose of ALCAR seems to synergize with the Adderall, while anything >300mg seems to compete with it.
Magnesium Orotate

N-Acetyl Cystine + mineral ascorbate (for glutathione production) is also extremely effective for neuroprotection, but at the price of effectively knocking out the effects of the Adderall and causing its own short-lived variety of brainfog.


However, after beginning a low-dose lithium orotate regimen, I was shocked at how remarkably powerful it is as both a neuroprotectant and mood stabilizer. Just 1-2mg elemental lithium (about 1/4 of a standard 120mg tablet) almost instantly eliminates virtually all acute (subjectively observable) syptoms of excitoxicity, stabilizes my mood and brain function, and optimizes my mental state for productive work and away from the hypomanic/OCD I usually experience when pulling stimulant-fueled all-niters.

Some caveats:
1) lithium orotate definitely inhibits some of the amphetamine euphoria (but not its ADHD therapeutic benefits), so if you're using/abusing your amphetamines just to get high then this isn't the solution you're looking for. (IMO 40mg PQQ is probably your best bet in that case)

2) It is incredibly potent, so only very small doses are required. If you take too much, in my case >2.5, it begins to significantly inhibit Adderall's therapeutic benefits essentially to the point of an unmedicated state. Start very very small (1/8 of a tablet) and work up as-needed to find the right balance for you.

3) The half life of lithium orotate is very long - something like 28 hours - so if you take too much and your Adderall stops working, you're pretty much screwed for at least the next day before any amount of amphetamine will start producing the desired effects again. Keep this in mind if testing it out when writing term papers or studying for exams. This is why I recommend starting low and working up.

Unequivocally, I believe that lithium orotate is the single most powerful neuroprotective supplement on the market (again, I've tried pretty much everything), and when used in very low doses appears to protect and optimize the brain - retain all the benefits of my Adderall while virtually eliminating the side effects.

I also believe that my blood pressure and sleep have also noticeably benefited.

Of note, I discussed the addition of lithium orotate to my regimen with my doctor at the university health center and described my early results, mostly to make sure it was safe, but also to get his thoughts on the potential therapeutic value for ADHD suffers on prescription stimulants like Adderall. He was highly enthusiastic, said there was absolutely no health concern whatsoever with the doses I was taking, and encouraged me to continue for as long as I thought it was helping.

I would STRONGLY encourage anyone regularly taking Adderall, Dexedrine, Vyvanse, or any street amphetamines to incorporate a low dose of lithium orotate into their regimen. I really cannot speak highly enough of it, and have found this thoroughly impressive supplement to be the single most over-the-counter neuroprotective solution to date.

Delta Gamma has been waiting on this report from me for like two months now and I didn't want to delay any longer. There are more thoughts I'd like to share when I get the chance, but until then let me know if anyone has specific questions and I'll do my best to answer in a timely fashion.

Edited by J. Galt, 20 April 2011 - 03:02 PM.

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