155 replies to this topic

[Delta Gamma]

I've noticed several threads on this forum dedicated to amphetamine in its various forms, but discerningly little to no information on how to prevent potential neurotoxicity. With that said, I do not use amphetamine though I do have several friends who have been using it for years as a AD(H)D treatment who lurk these boards.

There has been several findings recently suggesting negative outcomes for any sort of sustained amphetamine usage, even in the lower range of therapeutic doses.

• Increased risk of Parkinson's disease see a M&M discussion on the topic and study. There are several other studies exploring this link as well.
• A large loss in DA transported density, which may equivocate to cell death in primates given doses commonly seen in ADHD treatment. Ricaurte study and Bluelight discussion.

There are more studies indicating negative outcomes for (meth)amphetamine use, but the doses involved generally focus on abuse dosage patterns and non-primate studies. But, I'll spam with some links anyways.

A excellent review of mechanisms and relevance to humans

NMDA receptor, mematine, and reduction of amphetamine induced deficits
This is a great discussion on M&M about a potential treatment based on NMDA receptor antagonists and other relevant discussion. *waits for medievil to show up*

Another review of amphetamine neurotoxicity

Possible mechanism for amphetamine induced apoptosis

Rat study focusing on tyrosine hydroxylase and mRNA expression
I'm hoping you guys help out by posting more relevant studies.

Possible mechanisms for harm reduction:

• Stay cool, numerous studies have shown increased damage at higher temperatures (see below study).
• Antioxidants that can cross the BBB mitochondral support may be the key
• Asprin has been shown to work in rats though I'm unsure of human relevance
• Switch to methylphenidate its much less toxic
• 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.

There are several other approaches that have worked in animal models as well, such as mega doses of vitamins A,C,E, and D, treatment with hypnotics/sedatives, and antipsychotics. But, I haven't had time to review them.

My current recommendation for amphetamine users is this: take as low a dose as you can, eat blueberries, drink something cool, take a 100% RDA dose of vitamins A,C,E,D (this and the next step can be covered with a really good multivitamin), take some bioavailable magnesium and selenium (200mg elemental magnesium and the RDA of selenium), take some CoQ10 (lipid based capsule and at least 100mg), ALCAR may help but I haven't looked into it enough, and end your day with a 3-5mg dose of sublingual melatonin.

NOTE: I am not a MD, I have a background in cell biology, physiology, and pharmacology at the undergrad level. This is simply a guide made to show people potential routes of harm reduction.

All relevant information is appreciated.

Edited by Delta Gamma, 24 February 2011 - 10:52 PM.

[Delta Gamma]

Bump.

I would like to add that this thread is designed to deal with D-amphetamine toxicity, such as dexedrine and adderall though the latter is a 75-25 D/L- amphetamine split. Though many of these findings may apply to methamphetamine and to a lesser extent MDMA, some of the more exotic amphetamine derivatives could have some bizarre reactions that haven't been studied yet.

I'd also suggest some sort of voltage dependent NMDA receptor antagonist as a method of harm reduction, magnesium is the body's natural NMDA channel blocker but it isn't that effective in this kind of circumstance unless mega dosed. There is also a body of evidence suggesting NMDA antagonism can slow/reverse tolerance build up, which could have implications in dose reduction and reduced excitotoxicity.

Discussion on NMDA on tolerances in general:
http://www.longecity...806#entry436806
http://www.bluelight...NMDA antagonist

I'd like to add that long term amphetamine use can disrupt one's electrolyte balance, so perhaps supplementing things like Mn, Zn, Mg, and K would help improve the therapeutic outcome. I haven't found a solid source mentioning more than a single ion at a time, so I'm hoping you guys can dig one up.

Edited by Delta Gamma, 25 February 2011 - 08:17 PM.

[VoidPointer]

Bump.

I would like to add that this thread is designed to deal with D-amphetamine toxicity, such as dexedrine and adderall though the latter is a 75-25 D/L- amphetamine split. Though many of these findings may apply to methamphetamine and to a lesser extent MDMA, some of the more exotic amphetamine derivatives could have some bizarre reactions that haven't been studied yet.

Thanks for posting the collection of studies. I think many people choose Adderall because it generates more euphoria than methylphenidate, and because most young people do not like the fact that Concerta is usually the first med recommended by doctors. Since Concerta/Ritalin is also used to treat cocaine and meth addicts, it is perceived as a 'less fun' treatment, kind like the stimulant version of methadone.

The big pharmaceutical companies also want to make as much money as possible from the increasing number of ADD patients, and, since MPH has been around for 50 years, need create new, more profitable proprietary drugs.
It is a mystery to me why dexmethylphenidate is not more commonly used, as it is fairly new, and generally works better than standard MPH with less of the physical side effects.

[Delta Gamma]

Thanks for posting the collection of studies. I think many people choose Adderall because it generates more euphoria than methylphenidate, and because most young people do not like the fact that Concerta is usually the first med recommended by doctors. Since Concerta/Ritalin is also used to treat cocaine and meth addicts, it is perceived as a 'less fun' treatment, kind like the stimulant version of methadone.

The big pharmaceutical companies also want to make as much money as possible from the increasing number of ADD patients, and, since MPH has been around for 50 years, need create new, more profitable proprietary drugs.
It is a mystery to me why dexmethylphenidate is not more commonly used, as it is fairly new, and generally works better than standard MPH with less of the physical side effects.

Thanks, while I don't have any studies to back this up I believe the reason the dexmethylphenidate is not more widely used is due to a much faster tolerance development. I've browsed a few ADHD forums and M&M and it seems that the increased efficacy of the D-isomer only over the racemate is a trade off for increased tolerance development.

I'll fully agree that amphetamine is overused in the treatment of AD(H)D, DRI's, MAOI's, and DA agonists have all shown comparable efficacy with generally a better long term side effect profile. Nicotine even has a reasonably strong short term effect on AD(H)D. I'm still a little skeptical of strattera for ADHD, but there are some promising reviews out there aside from the reports of psychiatric events. I believe doctors should suggest dietary and lifestyle changes before jumping to medication that unfortunately many cannot get off.

As for big pharma, I'm not entirely convinced that its their fault for not producing new agents for AD(H)D as its a bit of a FDA nightmare to get approval for seeing as you're pretty much giving stimulants and dopagenics to the age groups most likely to abuse them, not to mention the now known effects of long term stimulant (ab)use.

[VoidPointer]

Thanks for posting the collection of studies. I think many people choose Adderall because it generates more euphoria than methylphenidate, and because most young people do not like the fact that Concerta is usually the first med recommended by doctors. Since Concerta/Ritalin is also used to treat cocaine and meth addicts, it is perceived as a 'less fun' treatment, kind like the stimulant version of methadone.

The big pharmaceutical companies also want to make as much money as possible from the increasing number of ADD patients, and, since MPH has been around for 50 years, need create new, more profitable proprietary drugs.
It is a mystery to me why dexmethylphenidate is not more commonly used, as it is fairly new, and generally works better than standard MPH with less of the physical side effects.

Thanks, while I don't have any studies to back this up I believe the reason the dexmethylphenidate is not more widely used is due to a much faster tolerance development. I've browsed a few ADHD forums and M&M and it seems that the increased efficacy of the D-isomer only over the racemate is a trade off for increased tolerance development.

I'll fully agree that amphetamine is overused in the treatment of AD(H)D, DRI's, MAOI's, and DA agonists have all shown comparable efficacy with generally a better long term side effect profile. Nicotine even has a reasonably strong short term effect on AD(H)D. I'm still a little skeptical of strattera for ADHD, but there are some promising reviews out there aside from the reports of psychiatric events. I believe doctors should suggest dietary and lifestyle changes before jumping to medication that unfortunately many cannot get off.

As for big pharma, I'm not entirely convinced that its their fault for not producing new agents for AD(H)D as its a bit of a FDA nightmare to get approval for seeing as you're pretty much giving stimulants and dopagenics to the age groups most likely to abuse them, not to mention the now known effects of long term stimulant (ab)use.

Interesting,, I have been on Focalin for almost two years (7.5 mg twice day or 15mg XR) and have not experienced too much tolerance. But when I do notice less effect I will take a few day 'vacation' and that seems to work. Also I sometimes will take Concerta instead, especially if I will be around people, rather than crunching numbers. Focalin can put one in a hyper-focus state where nothing matters other than the current problem.

In general anyone on stimulants needs to exercise,have a healthy diet, and take supplements such as CoQ10, DHA, and magnesium.

[InquilineKea]

Actually, coadministering Adderall with methylphenidate is one of the best ways to prevent Adderall-related neurotoxicity. A simple google search shows results: http://www.google.co...ethamphetamine. If it works for meth, it surely works even better for Adderall

==

Adderall's neurotoxicity is simply explained in this diagram: http://a1.sphotos.ak...7_386257_n.jpg. Dopamine auto-oxidation in the presynaptic neuron (which is the primary method of amphetamine's neurotoxicity) is completely unrelated to glutamate excitotoxicity. Sure, Adderall might increase glutamate levels (by some other mechanism), but these increases are not especially significant (and I suspect methylphenidate would do that too).

Edited by InquilineKea, 26 February 2011 - 11:15 AM.

[Delta Gamma]

Actually, coadministering Adderall with methylphenidate is one of the best ways to prevent Adderall-related neurotoxicity. A simple google search shows results: http://www.google.co...ethamphetamine. If it works for meth, it surely works even better for Adderall

==

Adderall's neurotoxicity is simply explained in this diagram: http://a1.sphotos.ak...7_386257_n.jpg. Dopamine auto-oxidation in the presynaptic neuron (which is the primary method of amphetamine's neurotoxicity) is completely unrelated to glutamate excitotoxicity. Sure, Adderall might increase glutamate levels (by some other mechanism), but these increases are not especially significant (and I suspect methylphenidate would do that too).

Thanks for the link, that's a avenue I didn't look into. Perhaps staggering the doses could optimize the treatment?
I'm more concerned with glutamate's role in tolerance development rather than its role in direct excitotoxicity, dose reduction helps avoid some of the oxidative stress inherent to amphetamine use. I've read a few reports saying that direct glutamate excitotoxicity is relevant in cases of gross amphetamine abuse, though I don't believe that it would have much relevance in most AD(H)D cases.

As for amphetamine's neurotoxicity being explained purely by dopamine auto-oxidation, I don't believe its that simple.
http://books.google....oxicity&f=false

[ultranaut]

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.

[rogerthat]

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!

Edited by rogerthat, 01 March 2011 - 12:10 AM.

[InquilineKea]

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

[rogerthat]

edit: sorry haha, meant the antioxidant link

[Delta Gamma]

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.

Edited by Delta Gamma, 01 March 2011 - 02:48 AM.

[Delta Gamma]

http://www.ncbi.nlm.nih.gov/pubmed/10987845

Neurotoxic effects of amphetamines, which are linked
to increased extracellular glutamate levels, are associated
with the production of ROS and can be attenuated by
antioxidants (Cadet and Brannock, 1998; Yamamoto and
Zhu, 1998; Yamamoto et al., 1998). Our results suggest
that ROS are also involved in the more modest increases
in VTA glutamate efflux produced by doses of amphetamine that lack overt neurotoxicity. First, we observed
that amphetamine-induced glutamate efflux was prevented when D-phenylalanine, a trapping agent for hydroxyl radicals, was included in the microdialysis perfusion solution. Second, it was prevented when a different
trapping agent, PBN, was injected systemically prior to
amphetamine administration. Given these findings, it is
puzzling that amphetamine-induced increases in hydroxyl radical levels were not detected in D-phenylalanine trapping studies. It is possible that amphetamine did
increase hydroxyl radical levels, but we could not detect
the increase either because of insensitivity or because of
side reactions that occurred more rapidly than trapping
by D-phenylalanine. A recent study using a different
trapping procedure (salicylate hydroxylation) was able to
detect a significant increase in hydroxyl radical formation when 10 mM amphetamine was infused into rat
striatum by reverse dialysis (Wan et al., 2000). This
concentration of amphetamine is sufficient to increase
VTA glutamate efflux (Wolf and Xue, 1998).

Hm interesting, so phenylalanine actually traps amphetamine-induced glutamate efflux. That might help with one portion of Adderall's neurotoxicity? (although not all of it).

Taken from a older thread on this board.

[ultranaut]

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?

I take generic dexedrine, I believe the doc prescribed it at 50mg per day. Each pill is 10mg so I have a lot of control over my dosing. I usually start with 10mg first thing in the morning and then work up from there if necessary. Some days I feel like ADHD is actually helpful, and some days my symptoms are better or worse than others. It's pretty rare for me to take more than 30mg.
Previously, I've been prescribed Vyvanse at 70mg and Adderall (I don't remember the dose but it was relatively high). Both worked noticeably better on my ADHD symptoms than every non-amphetamine treatment I've tried. I prefer the generic dexedrine because it's cheaper and easier to control dosing than with Vyvanse and has almost no side effects compared to Adderall.
I wish I'd been put on this stuff as a child, it would have radically improved my life.

[Delta Gamma]

I take generic dexedrine, I believe the doc prescribed it at 50mg per day. Each pill is 10mg so I have a lot of control over my dosing. I usually start with 10mg first thing in the morning and then work up from there if necessary. Some days I feel like ADHD is actually helpful, and some days my symptoms are better or worse than others. It's pretty rare for me to take more than 30mg.
Previously, I've been prescribed Vyvanse at 70mg and Adderall (I don't remember the dose but it was relatively high). Both worked noticeably better on my ADHD symptoms than every non-amphetamine treatment I've tried. I prefer the generic dexedrine because it's cheaper and easier to control dosing than with Vyvanse and has almost no side effects compared to Adderall.
I wish I'd been put on this stuff as a child, it would have radically improved my life.

That's on the high side for dosing, so if I were you I would start taking some extra preventative steps. One of the easiest ways to increase your protection is to have a diet rich in dark fruits and vegetables, so I would suggest drinking a lot of 100% blueberry juice or something similar. Curcumin and CoQ10/ubiquinol are also somethings I would recommend as they have long halflives (20+ hours IIRC) and potent radical scavenging effects in addition to various positive actions on mitochondrial function. Also, perhaps dosing 250-500mg L-phenylalanine at night would help prevent possible catecholamine depletion and *fingers crossed* neurotoxicity via the mechanism described in the post I quoted.

Maintaining a healthy diet and taking the proper multivitamin should also be something you should focus on, as well as aerobic exercise as they all will help your body's natural antioxidant mechanisms. There is evidence that Bacopa monnieri can upregulate superoxide dismutase in rats, so it may be a worthwhile option to supplement if you don't have a negative reaction to it.

http://www.ncbi.nlm....pubmed/12410544
http://gradworks.umi...50/3350067.html

Here's a great blog I found while I was hunting for some more content to post:
http://undergroundph...-reversing.html
Looks like its run by a bunch of bluelight.ru people.

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 and I am drawing my information from as wide a publicly available range I can. This is educated conjecture based on the assumptions that results from in vivo studies in various mammals and various in vitro studies carry over to humans. I will do my best to mention the various approaches which will likely transfer over to humans with few known side effects, but the onus is on you the reader to ensure that these courses of action are right for you. To the best of my knowledge there has been little to no research in amphetamine neurotoxicity in humans outside of cases of gross abuse.

[owls]

you guys are crazy... you're probably causing more oxidative stress just by thinking so hard over what should be a non-issue...

if you're that worried about amphetamine neurotoxicity at PRESCRIBED dosages, take 5 grams of vitamin C and/or other antioxidants a day and you'll be fine... hypochondriacs up in this place

[Delta Gamma]

you guys are crazy... you're probably causing more oxidative stress just by thinking so hard over what should be a non-issue...

if you're that worried about amphetamine neurotoxicity at PRESCRIBED dosages, take 5 grams of vitamin C and/or other antioxidants a day and you'll be fine... hypochondriacs up in this place

Hahaha well maybe my concerns aren't totally valid until more studies come out, this is a forum for people who want to live forever so I feel its worth writing in this thread.

This is probably the best recent review I've seen for ADHD relevant dosage patterns, therefore: READ!
http://jad.sagepub.c...11/1/8.full.pdf

I would also like to add that amphetamine toxicity is not profound if used responsibly and basic care is taken by the user. Amphetamine is a very old drug with a large history of (ab)use in humans, if it caused significant and sudden neurotoxcity at responsible usage patterns then we would probably know. Look at all the (meth)amphetamine used in WWII, and its use in ADHD treatment for decades.

I'm saying this so people who are on low dose amphetamine don't freak out and overdo potential harm reduction measures, but I'm also saying this so people realize that perhaps these potential harm reduction measures may benefit them in the long run. This is also the reason I have not discussed MAOI based options yet as well, as they have a large chance to do more harm than good if improperly used.

[ultranaut]

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.

[J. Galt]

PQQ is neuroprotective and does wonders to reduce brain fog during adderall-induced all-niters. Aside from it the immediate benefits of its neuroprotective and NMDA modulating effects, it dramatically improves mitochondrial function (especially in the brain). Most importantly, it stimulates the growth of NEW mitochondria.

IMO, one of the most effective means of reducing and reversing damage from d-amp and Adderall (which in my case was severe) is to support mitochondrial health. In addition to PQQ, I've had great results with ubiquinol + Shilajit, Quinogel (hydrsoluble ubiquinol), ALCAR, GPLC, NADH, D-Ribose, Sodium R-Lipoic acid, and magnesium (elemental, glycerinate, or citrate).

Experientially speaking, Adderall seems to take a massive toll on mitochondrial function, especially when used excessively to avoid sleep. By targeting mitochondrial support with my supplement regimen, I have dramatically reversed much of the perceived cognitive decline caused by three years of heavy Adderall use and (eventually) abuse. I also feel that this stack has been helpful in preventing further damage from continued amphetamine use.

Planetary Herbals' Schizandra Adrenal Complex is incredibly helpful to take at night. This cured my severe adrenal fatigue, and I now use it daily for maintenance. Isocort - used OCCASIONALLY in times of heavy adderall use / adrenal stress - is also very helpful in restoring and maintainig proper adrenal function during chronic amphetamine use.

L-Carnosine, Sam-e, Sulbutiamine, astaxanthin, calcium ascorbate, Opti-Zinc, a vitamin K2 complex (M4 and M7), green tea phytosome, and Siliphos (milk thistle phytosome) have also seemed to help with a lot damage reduction, as has the homocystine lowering stack of P-5-P, methylcobalamin, L-methylfolate and/or megafolinic (advanced forms of folic acid), and TMG.

I also take SAMe for about one week out of the month, which seems to help restore neurotransmitter balance (IMO, not sure if there is research to support this).

Adderall can cause GABA and melatonin deficiencies, especially when used for all-niters. Taking 1-3mg melatonin, 200mg GABA, and 25mg 5-htp before bed has helped me to reclaim more healthy and restorative sleep patterns.

Hyland's homeopathic Nerve tonic is great at bedtime and really seems to help repair and refresh my nervous system overnight. It used to take me at least half an hour or more to wake up in the morning, and I used to need coffee or adderall just to get going. Since adding the Nerve Tonic and the Schizandra complex to my nighttime regimen, I now wake up feeling refreshed and recharged, usually before my alarm even goes off.

Tried Memantine for about a month over Christmas break, during which I abstained from all amphetamine use. I followed the recommended protocol of titrating up from 5mg to eventually 30mg daily by the end of the break, and continued for about another week once resuming adderall use for the spring semester. To my disappointment, it did very little to reverse my existing adderall tolerance and if anything seemed to blunt its effects. I know others have had great results here, but IMO it was not worth the cost.

Of everything that I've tried, PQQ is the most recent addition and seems to be the single most effective component. The results are pretty dramatic, especially at the 20-40mg/day range. Unfortunately it's kind of expensive, but if you shop around you can usually find the Life Extensiom brand BioPQQ brand for about $15 total (inc shipping) per 30-count 10mg bottle.

Additionally, I try to take at least 1-2 days off Adderall/Dexedrine every weekend. On these days I take 700mg alpha-gpc, 500mg Citicoline, and various race tams (cycled). This seems to help my brain repair itself from the stresses of the previous week and let's me start the next one feeling mentally refreshed.

I'm still way too dependent on Adderall and am working to address this, and it seriously messed me up for the better part of last year, but this regimen has fortunately helped to reverse much of the damage already, keep further tolerance buildup under control, and appears to be keeping most further damage at bay. Adderall has seriously damaged my mental and physical health, and for at least a year sucked all happiness out of my life. This stack has allowed to regain control of my life, and has converted an increasingly debilitating addiction into a functional and manageable one.

Hopefully others will will find some of it useful. Feel free to PM me with any specific questions.

[Delta Gamma]

PQQ is neuroprotective and does wonders to reduce brain fog during adderall-induced all-niters. Aside from it the immediate benefits of its neuroprotective and NMDA modulating effects, it dramatically improves mitochondrial function (especially in the brain). Most importantly, it stimulates the growth of NEW mitochondria.

IMO, one of the most effective means of reducing and reversing damage from d-amp and Adderall (which in my case was severe) is to support mitochondrial health. In addition to PQQ, I've had great results with ubiquinol + Shilajit, Quinogel (hydrsoluble ubiquinol), ALCAR, GPLC, NADH, D-Ribose, Sodium R-Lipoic acid, and magnesium (elemental, glycerinate, or citrate).

Experientially speaking, Adderall seems to take a massive toll on mitochondrial function, especially when used excessively to avoid sleep. By targeting mitochondrial support with my supplement regimen, I have dramatically reversed much of the perceived cognitive decline caused by three years of heavy Adderall use and (eventually) abuse. I also feel that this stack has been helpful in preventing further damage from continued amphetamine use.

Planetary Herbals' Schizandra Adrenal Complex is incredibly helpful to take at night. This cured my severe adrenal fatigue, and I now use it daily for maintenance. Isocort - used OCCASIONALLY in times of heavy adderall use / adrenal stress - is also very helpful in restoring and maintainig proper adrenal function during chronic amphetamine use.

L-Carnosine, Sam-e, Sulbutiamine, astaxanthin, calcium ascorbate, Opti-Zinc, a vitamin K2 complex (M4 and M7), green tea phytosome, and Siliphos (milk thistle phytosome) have also seemed to help with a lot damage reduction, as has the homocystine lowering stack of P-5-P, methylcobalamin, L-methylfolate and/or megafolinic (advanced forms of folic acid), and TMG.

I also take SAMe for about one week out of the month, which seems to help restore neurotransmitter balance (IMO, not sure if there is research to support this).

Adderall can cause GABA and melatonin deficiencies, especially when used for all-niters. Taking 1-3mg melatonin, 200mg GABA, and 25mg 5-htp before bed has helped me to reclaim more healthy and restorative sleep patterns.

Hyland's homeopathic Nerve tonic is great at bedtime and really seems to help repair and refresh my nervous system overnight. It used to take me at least half an hour or more to wake up in the morning, and I used to need coffee or adderall just to get going. Since adding the Nerve Tonic and the Schizandra complex to my nighttime regimen, I now wake up feeling refreshed and recharged, usually before my alarm even goes off.

Tried Memantine for about a month over Christmas break, during which I abstained from all amphetamine use. I followed the recommended protocol of titrating up from 5mg to eventually 30mg daily by the end of the break, and continued for about another week once resuming adderall use for the spring semester. To my disappointment, it did very little to reverse my existing adderall tolerance and if anything seemed to blunt its effects. I know others have had great results here, but IMO it was not worth the cost.

Of everything that I've tried, PQQ is the most recent addition and seems to be the single most effective component. The results are pretty dramatic, especially at the 20-40mg/day range. Unfortunately it's kind of expensive, but if you shop around you can usually find the Life Extensiom brand BioPQQ brand for about $15 total (inc shipping) per 30-count 10mg bottle.

Additionally, I try to take at least 1-2 days off Adderall/Dexedrine every weekend. On these days I take 700mg alpha-gpc, 500mg Citicoline, and various race tams (cycled). This seems to help my brain repair itself from the stresses of the previous week and let's me start the next one feeling mentally refreshed.

I'm still way too dependent on Adderall and am working to address this, and it seriously messed me up for the better part of last year, but this regimen has fortunately helped to reverse much of the damage already, keep further tolerance buildup under control, and appears to be keeping most further damage at bay. Adderall has seriously damaged my mental and physical health, and for at least a year sucked all happiness out of my life. This stack has allowed to regain control of my life, and has converted an increasingly debilitating addiction into a functional and manageable one.

Hopefully others will will find some of it useful. Feel free to PM me with any specific questions.

Great post man, if you could dig up some studies on PQQ that would be great. I'm assuming you're talking about pyrroloquinoline quinone when you say PQQ, am I right?
http://en.wikipedia....inoline_quinone

I'm a big fan of mitochondrial support for amphetamine harm reduction so its great to see someone else focus on the apoptosis inducing action rather than the triggers for it. If you wouldn't mind posting some relevant studies that would be really appreciated. I feel it would be great for several of my friends' and the amphetamine using population as a whole if a large and detailed thread on amphetamine neurotoxicity and induced deficits rather than the small and quickly dying/dead ones that appear on a current google search.

I would say that another interesting supplement for amphetamine's effect on nNOS (a enzyme which produces reactive nitrogen species and NO) could be inosine due to its peroxynitrite scavenging ability. Also from reading some spinal cord injury related studies on it it appears to improve axonal rewiring which could also help reroute damaged pathways within the brain. I'd need to do a lot more searching before I give any recommendation for its use or not, though it seems pretty damn safe.

As for neurotransmitter deletion, it appears that a lot of the difficulties that are associated with replenishing catecholamines after/during amphetamine use is damage to tyrosine hydroxylase, so L-DOPA could be a (risky) but likely option. SAMe has some interesting effects on DA levels and NE levels though I haven't got the figures off the top of my head, if you could dig something up that would let everyone do some reading on this kind of thing.

Edited by Delta Gamma, 04 March 2011 - 12:43 PM.

[Delta Gamma]

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.

One thing that jumps out at me when you mentioned ECGC is its COMT inhibition. If you're the kind of person who experiences peripheral side effects (vasoconstriction, intestinal disturbances, impotence/peanut sized junk etc.) I can see it increasing them as can curcumin due to its MAOI effects. Your stack other than that looks pretty solid, only thing I would recommend adding is magnesium and a decent multivitamin (preferably low in iron).

As for the RC's it could be pretty much harmless depending on the type you're using, synthetic cannabinoids and designer stims/dissociatives may have VERY negative long term outcomes as with the psychedelic amphetamines. Though the latter is more just conjecture on my part, most of the non-amphetamine phenethylamines seem reasonably safe barring the 2C-T-X series (or really anything with a thio ester on that postion) due to possible MAO-A inhibition.

Fun fact: iron ions are the cofactor needed for both dopamine synthesis and auto-oxidation, curcumin chelates iron (read:binds to it and makes it biologically inactive). http://www.ncbi.nlm....pubmed/16545682

[J. Galt]

PQQ is neuroprotective and does wonders to reduce brain fog during adderall-induced all-niters. Aside from it the immediate benefits of its neuroprotective and NMDA modulating effects, it dramatically improves mitochondrial function (especially in the brain). Most importantly, it stimulates the growth of NEW mitochondria.

IMO, one of the most effective means of reducing and reversing damage from d-amp and Adderall (which in my case was severe) is to support mitochondrial health. In addition to PQQ, I've had great results with ubiquinol + Shilajit, Quinogel (hydrsoluble ubiquinol), ALCAR, GPLC, NADH, D-Ribose, Sodium R-Lipoic acid, and magnesium (elemental, glycerinate, or citrate).

Experientially speaking, Adderall seems to take a massive toll on mitochondrial function, especially when used excessively to avoid sleep. By targeting mitochondrial support with my supplement regimen, I have dramatically reversed much of the perceived cognitive decline caused by three years of heavy Adderall use and (eventually) abuse. I also feel that this stack has been helpful in preventing further damage from continued amphetamine use.

Planetary Herbals' Schizandra Adrenal Complex is incredibly helpful to take at night. This cured my severe adrenal fatigue, and I now use it daily for maintenance. Isocort - used OCCASIONALLY in times of heavy adderall use / adrenal stress - is also very helpful in restoring and maintainig proper adrenal function during chronic amphetamine use.

L-Carnosine, Sam-e, Sulbutiamine, astaxanthin, calcium ascorbate, Opti-Zinc, a vitamin K2 complex (M4 and M7), green tea phytosome, and Siliphos (milk thistle phytosome) have also seemed to help with a lot damage reduction, as has the homocystine lowering stack of P-5-P, methylcobalamin, L-methylfolate and/or megafolinic (advanced forms of folic acid), and TMG.

I also take SAMe for about one week out of the month, which seems to help restore neurotransmitter balance (IMO, not sure if there is research to support this).

Adderall can cause GABA and melatonin deficiencies, especially when used for all-niters. Taking 1-3mg melatonin, 200mg GABA, and 25mg 5-htp before bed has helped me to reclaim more healthy and restorative sleep patterns.

Hyland's homeopathic Nerve tonic is great at bedtime and really seems to help repair and refresh my nervous system overnight. It used to take me at least half an hour or more to wake up in the morning, and I used to need coffee or adderall just to get going. Since adding the Nerve Tonic and the Schizandra complex to my nighttime regimen, I now wake up feeling refreshed and recharged, usually before my alarm even goes off.

Tried Memantine for about a month over Christmas break, during which I abstained from all amphetamine use. I followed the recommended protocol of titrating up from 5mg to eventually 30mg daily by the end of the break, and continued for about another week once resuming adderall use for the spring semester. To my disappointment, it did very little to reverse my existing adderall tolerance and if anything seemed to blunt its effects. I know others have had great results here, but IMO it was not worth the cost.

Of everything that I've tried, PQQ is the most recent addition and seems to be the single most effective component. The results are pretty dramatic, especially at the 20-40mg/day range. Unfortunately it's kind of expensive, but if you shop around you can usually find the Life Extensiom brand BioPQQ brand for about $15 total (inc shipping) per 30-count 10mg bottle.

Additionally, I try to take at least 1-2 days off Adderall/Dexedrine every weekend. On these days I take 700mg alpha-gpc, 500mg Citicoline, and various race tams (cycled). This seems to help my brain repair itself from the stresses of the previous week and let's me start the next one feeling mentally refreshed.

I'm still way too dependent on Adderall and am working to address this, and it seriously messed me up for the better part of last year, but this regimen has fortunately helped to reverse much of the damage already, keep further tolerance buildup under control, and appears to be keeping most further damage at bay. Adderall has seriously damaged my mental and physical health, and for at least a year sucked all happiness out of my life. This stack has allowed to regain control of my life, and has converted an increasingly debilitating addiction into a functional and manageable one.

Hopefully others will will find some of it useful. Feel free to PM me with any specific questions.

Great post man, if you could dig up some studies on PQQ that would be great. I'm assuming you're talking about pyrroloquinoline quinone when you say PQQ, am I right?
http://en.wikipedia....inoline_quinone

I'm a big fan of mitochondrial support for amphetamine harm reduction so its great to see someone else focus on the apoptosis inducing action rather than the triggers for it. If you wouldn't mind posting some relevant studies that would be really appreciated. I feel it would be great for several of my friends' and the amphetamine using population as a whole if a large and detailed thread on amphetamine neurotoxicity and induced deficits rather than the small and quickly dying/dead ones that appear on a current google search.

I would say that another interesting supplement for amphetamine's effect on nNOS (a enzyme which produces reactive nitrogen species and NO) could be inosine due to its peroxynitrite scavenging ability. Also from reading some spinal cord injury related studies on it it appears to improve axonal rewiring which could also help reroute damaged pathways within the brain. I'd need to do a lot more searching before I give any recommendation for its use or not, though it seems pretty damn safe.

As for neurotransmitter deletion, it appears that a lot of the difficulties that are associated with replenishing catecholamines after/during amphetamine use is damage to tyrosine hydroxylase, so L-DOPA could be a (risky) but likely option. SAMe has some interesting effects on DA levels and NE levels though I haven't got the figures off the top of my head, if you could dig something up that would let everyone do some reading on this kind of thing.

Here are two decent overviews on PQQ from LEF (w/supporting citations):
http://search.lef.or...Pqq&hiword=Pqq
http://search.lef.or...Pqq&hiword=Pqq

Your suggestion about inosine is interesting. I'm not very familiar with the supplement. Any good articles or research you can provide would be appreciated.

[Delta Gamma]

Your suggestion about inosine is interesting. I'm not very familiar with the supplement. Any good articles or research you can provide would be appreciated.

I was more looking at the unaddressed issue of RNS in amphetamine usage due to Ca2+ influx activating iNOS (not nNOS my bad)something which PQQ appears to do in spades. Inosine might still be a option but given my recent insomnia I don't have the motivation to research.

[Delta Gamma]

And, after 3 hours sleep I emerge fresh as a daisy:

http://www.pnas.org/...99/13/9031.full Axonal rewiring after a stroke.
http://www.sciencedi...1b&searchtype=a Some info on the cellular mechanisms of axonal rewiring.
http://www.sciencedi...30&searchtype=a A review suggesting potent neuroprotective and immunomodulating effects, safety in humans (we're talking piracetam safe here), potential uses in autoimmune diseases, and a increase in uric acid (one of the body's main antioxidants and also the cause of gout).

http://www.sciencedi...9f&searchtype=a Looks like it mediates its effects at least partly by being a adenosine receptor agonist. This might mean drowsiness at heroic dosages, but human trials didn't report it or I didn't find any yet.

And as a interesting side note, protects against diabetes in mice (leaving this here for a certain someone).
http://joe.endocrino...t/198/3/581.pdf

However, in one of the few human trials I could find it did not seem to prevent the progression of MS. If this is relevant or not to amphetamine usage I don't know, but its worth posting as it shows there has been some long-ish term human use. Though, preliminary trials showed potential improvement in MS patients over 11+ months.
http://www.accelerat...:8080/node/3587

[J. Galt]

However, in one of the few human trials I could find it did not seem to prevent the progression of MS. If this is relevant or not to amphetamine usage I don't know, but its worth posting as it shows there has been some long-ish term human use. Though, preliminary trials showed potential improvement in MS patients over 11+ months.
http://www.accelerat...:8080/node/3587

Interesting abstracts. Thanks for posting.

I am not aware of any significant connection or similarity between MS and amphetamine neurotoxicity. It is intimately
related to Parkinson's however, as the primary mechanism of cell death in this disease is nearly identical to that caused by amphetamine excitotoxicity.

Any thoughts on uridine (UMP) supplementation during amphetamine use as a peroxynitrate scavenger? Would taking it in addition to Citicoline be redundant?

[J. Galt]

Great post man, if you could dig up some studies on PQQ that would be great. I'm assuming you're talking about pyrroloquinoline quinone when you say PQQ, am I right?
http://en.wikipedia....inoline_quinone

I'm a big fan of mitochondrial support for amphetamine harm reduction so its great to see someone else focus on the apoptosis inducing action rather than the triggers for it. If you wouldn't mind posting some relevant studies that would be really appreciated. I feel it would be great for several of my friends' and the amphetamine using population as a whole if a large and detailed thread on amphetamine neurotoxicity and induced deficits rather than the small and quickly dying/dead ones that appear on a current google search.

I would say that another interesting supplement for amphetamine's effect on nNOS (a enzyme which produces reactive nitrogen species and NO) could be inosine due to its peroxynitrite scavenging ability. Also from reading some spinal cord injury related studies on it it appears to improve axonal rewiring which could also help reroute damaged pathways within the brain. I'd need to do a lot more searching before I give any recommendation for its use or not, though it seems pretty damn safe.

As for neurotransmitter deletion, it appears that a lot of the difficulties that are associated with replenishing catecholamines after/during amphetamine use is damage to tyrosine hydroxylase, so L-DOPA could be a (risky) but likely option. SAMe has some interesting effects on DA levels and NE levels though I haven't got the figures off the top of my head, if you could dig something up that would let everyone do some reading on this kind of thing.

Here are two decent overviews on PQQ from LEF (w/supporting citations):
http://search.lef.or...Pqq&hiword=Pqq
http://search.lef.or...Pqq&hiword=Pqq

Your suggestion about inosine is interesting. I'm not very familiar with the supplement. Any good articles or research you can provide would be appreciated.

Ordered some inosine today on your suggestion Delta Gamma. Will report if I can discern any effects.

[Delta Gamma]

However, in one of the few human trials I could find it did not seem to prevent the progression of MS. If this is relevant or not to amphetamine usage I don't know, but its worth posting as it shows there has been some long-ish term human use. Though, preliminary trials showed potential improvement in MS patients over 11+ months.
http://www.accelerat...:8080/node/3587

Interesting abstracts. Thanks for posting.

I am not aware of any significant connection or similarity between MS and amphetamine neurotoxicity. It is intimately
related to Parkinson's however, as the primary mechanism of cell death in this disease is nearly identical to that caused by amphetamine excitotoxicity.

Any thoughts on uridine (UMP) supplementation during amphetamine use as a peroxynitrate scavenger? Would taking it in addition to Citicoline be redundant?

I don't believe it has much to do directly with amphetamine neurotoxicity either, though there is some evidence that stimulant abuse can lead to demyelination in specific brain regions. http://www.ncbi.nlm....pubmed/15009677
I more just wanted to post the results of the long term study on it.

That also led me to stumble upon a really interesting neuropeptide: Cocaine and Amphetamine Regulated Transcript (CART) http://en.wikipedia....ted_transcript. We're currently covering peptide messangers in my pharmacology class, so I'll post more on it if I learn anything about it in class.

As far as citicoline goes, it might work as a peroxynitrate scavenger though I haven't done any research on it.

It'll be great to get a report on inosine usage with amphetamine J. Galt! However, I'd look up the symptoms of gout just to be on the safe side if I were you. It doesn't seem too likely, but it is known to increase uric acid levels which is the cause of gout.

[ultranaut]

One thing that jumps out at me when you mentioned ECGC is its COMT inhibition. If you're the kind of person who experiences peripheral side effects (vasoconstriction, intestinal disturbances, impotence/peanut sized junk etc.) I can see it increasing them as can curcumin due to its MAOI effects. Your stack other than that looks pretty solid, only thing I would recommend adding is magnesium and a decent multivitamin (preferably low in iron).

I do experience some minor peripheral side effects from amphetamines, primarily vasoconstriction-induced erectile dysfunction (aka, "is it scared to come out and play?"). The l-amp in Adderal particularly does this even at relatively small doses but they all do it to some extent and/or in some circumstances. I haven't noticed EGCG or curcumin increasing this effect but it's not something I've paid close attention to. I was actually under the impression that COMT inhibition could potentially reduce peripheral side effects but I don't remember why I had that idea. Generally, with my current stack and dosing schedule I've got things under control well enough that peripheral side effects are predictably minimal, infrequent, and almost never disruptive to performing necessary tasks.

[Delta Gamma]

One thing that jumps out at me when you mentioned ECGC is its COMT inhibition. If you're the kind of person who experiences peripheral side effects (vasoconstriction, intestinal disturbances, impotence/peanut sized junk etc.) I can see it increasing them as can curcumin due to its MAOI effects. Your stack other than that looks pretty solid, only thing I would recommend adding is magnesium and a decent multivitamin (preferably low in iron).

I do experience some minor peripheral side effects from amphetamines, primarily vasoconstriction-induced erectile dysfunction (aka, "is it scared to come out and play?"). The l-amp in Adderal particularly does this even at relatively small doses but they all do it to some extent and/or in some circumstances. I haven't noticed EGCG or curcumin increasing this effect but it's not something I've paid close attention to. I was actually under the impression that COMT inhibition could potentially reduce peripheral side effects but I don't remember why I had that idea. Generally, with my current stack and dosing schedule I've got things under control well enough that peripheral side effects are predictably minimal, infrequent, and almost never disruptive to performing necessary tasks.

COMT and MAOI break down catecholamines, so inhibiting them peripherally can result in increased vasoconstriction unless you're a weird one with more DA than EP/NE in their circulation. Gingko is a safe vasodilator if you want to try it out, as is CoQ10.

Though ECGC can also decrease the amount of peripheral catecholamines synthesized via DOPA decarboxylase inhibition. Really depends on the individual and the dose.

Edited by Delta Gamma, 07 March 2011 - 11:48 PM.

[Delta Gamma]

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7CV6-4B2Y980-28&_user=1067472&_coverDate=12%2F31%2F2002&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_searchStrId=1667015346&_rerunOrigin=scholar.google&_acct=C000051251&_version=1&_urlVersion=0&_userid=1067472&
md5=62c17bf8d82c761acca2c296bd9c4e1b&searchtype=a Some info on the cellular mechanisms of axonal rewiring.

http://www.sciencedi...30&searchtype=a

A review suggesting potent neuroprotective and immunomodulating effects, safety in humans (we're talking piracetam safe here), potential uses in autoimmune diseases, and a increase in uric acid (one of the body's main antioxidants and also the cause of gout).

http://www.sciencedi...9f&searchtype=a

Looks like it mediates its effects at least partly by being a adenosine receptor agonist. This might mean drowsiness at heroic dosages, but human trials didn't report it or I didn't find any yet.

It appears that the science direct links don't work for most people, so here's some info to find the full articles, the one below quotes all the interesting bits from the other links that don't work.

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

Inosine is a safe, naturally occurring purine that appears to be non-toxic to humans, even when ingested at doses as high as 10 g kg−1 day−1

Like I said, its pretty freaking safe haha, even those guys on 40g piracetam a day would probably have issues wolfing down the 700g of this stuff that would likely cause issues.