Amphetamine Neurotoxicity and Tolerance Reduction/Prevention III

[Epsilon Alpha]

I'd love to just know a stack that you'd recommend to those of us who are on it purely for ADD (which I am) as the last thing I want is Parkinson or a stuffed short term memory because of the very thing that is trying to help my focus and memory. I'm really guessing at the moment plucking pieces of information out of threads all over the internet and spend so much money on supplements, some just to find out it's doing more harm than good after it has been updated.

Reduced tolerance to me is just a bonus, the main things is protecting my brain to start with or repairing the damage it has done.

Love to hear this from you EA as you seem to be the most proactive on the subject to protect ones self from harm whilst taking this medication. Again ONLY ADD / ADHD doses.

I'm mostly taking modafinil now, as the anorexic effects of amphetamine (20-40mg Vyvanse) were really throwing me off. I still take the odd dose when my sleep is really off, but I've gotten that mostly under control now. As a side note, low dose valprotic acid (250mg a night) has completely fixed my insomnia and I'm without any other symptoms indicative of a mood disorder. Wish I found this out years ago!

My personal stack with amphetamine is: 100mg CoQ10 (this particular brand has 200mg omega 3 fatty acids in it), a men's multivitamin, and usually a bit more fruit than I'd normally eat. Costs me maybe $15 a month, maybe a bit more if I decide to use 1-5mg melatonin in the evening. I alternate caffeine and amphetamine when I do need a pick me up during call, but I'm trying to keep the medications to a minimum.

I do find CoQ10 while not really doing much for the "built up" tolerance it stops it from growing near as fast as it normally would. Proper nutrition is also a big thing for me, if I don't get my 5 servings of fruit and vegetables I find my crash is much harder. For daily low doses there really doesn't seem to be a magic bullet for tolerance or toxicity, but extrapolating from Parkinson's studies CoQ10, a healthy diet, and exercise all seem to be key points. For massive acute usage the literature lends itself a bit more to speculation on stacks, but more and more it looks like its just best to avoid that usage pattern.

 

[Epsilon Alpha]

Here's a really good free paper on our current understanding of methamphetamine toxicity, covers some interesting topics that I haven't addressed in this thread like the role of the D3 receptor, neuroinflammation and p53.

ABSTRACT:Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.

http://www.ncbi.nlm.nih.gov/pubmed/25861156

 

[PsychedelicWizard]

Basically if you use them in low doses at therapeutic levels, you can use them daily for years and they will actually promote healthy neurological growth by creating new neural pathways. If, however, you are like me and most people, you can't stop at just one chip, so you will pop them to get high and love it so much you will keep doing it. This then fries your dopamine receptors like basically overclocking a computer and causing it to malfunction from too much heat.

The more damage these receptors take, the more of the drug you will need to have them fire as hard as you want, and thus even more damage is done until your highs and lows finally reach their capacity, and the lows go from being sort of down to hellishly depressed and the highs go from being having a good buzz to on cloud fuckin' 9, and if you stop using, you will initially only go to a much lower place than before you used stims, it will take you a long time to reach the flat mediocre states of emotional consistency again, but as most people are going up the really slow elevator to repairing the brain and going from being always low to contentment, they will almost always relapse to escape their torment, but that resets the cycle.

The truth is there is nothing you can do under current medical science to alter the process. The more you get high on amphetamines, the less happy you will be without them, really is that simple. Not to mention the norephedrine and adrenaline and other chemicals affected that can make you suddenly anxious, restless, or emotionally volatile because while those receptors aren't damaged as heavily, they end up getting set way out of whack as the other receptors heal.

To be free of this cycle, is to repair the dopamine and norephedrine generating neurotransmitters, and get the other fluctuating over-compensating chemicals to even out. All you can really do is wait. Time will heal it. A proper diet, exercise, sunlight, cognitive therapy, love, and social support will make it heal a significant amount faster, but really, it is just time.

You can use other drugs to deal with the comedowns.

TLDR:

If you casually abuse stims like one a week at the club, you can literally do it for years and never have much problem, but if you start being a daily, chronic user, you get in a really hard situation where you are either stay on it for the long haul or go through a shitty few months to be free.

Basically kids, do you want to experience more happiness than ever before? Then start abusing amphetamines, but if on the other hand you want to never experience true mental hell, then don't? Really just a choice. But I guarantee you won't ever experience the same thrill without them, but once you taste it, you can never truly go back.

 

[Beings]

"dopamine and norephedrine generating neurotransmitters" great gem.


"The truth is there is nothing you can do under current medical science to alter the process. The more you get high on amphetamines, the less happy you will be without them, really is that simple".

Thanks for summing up current medical science I guess you could take less, less often, but the process is not that simple. Anyways, not trying to be a dick, but dont write authoritatively in ADD, when you are mostly providing self account of your experiences.

 

[PsychedelicWizard]

"dopamine and norephedrine generating neurotransmitters" great gem.


"The truth is there is nothing you can do under current medical science to alter the process. The more you get high on amphetamines, the less happy you will be without them, really is that simple".

Thanks for summing up current medical science I guess you could take less, less often, but the process is not that simple. Anyways, not trying to be a dick, but dont write authoritatively in ADD, when you are mostly providing self account of your experiences.

Actually it is that simple. When you pump the brain full of dopamine, it stops producing dopamine naturally anymore. I don't really see how this is a hard concept to grasp.

The brain produces a chemical based on external stimuli, thought, however it works, but seems people do not produce enough, which it then corrects.

But if you start using a high dose regularly, far beyond what is therapeutic, the brain simply stops producing as much dopamine, and the receptors do get damaged by that kind of activity.

Need proof? Find someone who has never touched amphetamine and measure their brain activity when they are doing something that is not rewarding, and again when they are doing a rewarding activity. Now get them 10 years later after chronic heavy abuse and do the same type of experiment.

All of psychiatry and neuro-science depends on anecdotal evidence, because we don't have sophisticated enough technology to conduct proper experiments yet.

Neuro-science is a very new field that barely has any real data on anything. But I am a chronic heavy stimulant user, and I know that I have tried stopping for a few weeks, and my baseline happiness while not using is much lower than before I started, but while using, it is much higher.

If you need more proof, just look at Johnny Cash or other celebrities, it is the inevitable cycle.

But if you used it at lesser doses, it certainly can actually improve dopamine-producing activity, but use it to get high all the time and you are caught in a loop that is very very difficult to break. The good news is that your brain can literally repair any kind of damage to these neuro-transmitters and receivers, but it takes time, and it is very hard to not relapse during this time period.

 

[Epsilon Alpha]

Actually it is that simple. When you pump the brain full of dopamine, it stops producing dopamine naturally anymore. I don't really see how this is a hard concept to grasp.

The brain produces a chemical based on external stimuli, thought, however it works, but seems people do not produce enough, which it then corrects.

But if you start using a high dose regularly, far beyond what is therapeutic, the brain simply stops producing as much dopamine, and the receptors do get damaged by that kind of activity.

Need proof? Find someone who has never touched amphetamine and measure their brain activity when they are doing something that is not rewarding, and again when they are doing a rewarding activity. Now get them 10 years later after chronic heavy abuse and do the same type of experiment.

All of psychiatry and neuro-science depends on anecdotal evidence, because we don't have sophisticated enough technology to conduct proper experiments yet.

Neuro-science is a very new field that barely has any real data on anything. But I am a chronic heavy stimulant user, and I know that I have tried stopping for a few weeks, and my baseline happiness while not using is much lower than before I started, but while using, it is much higher.

If you need more proof, just look at Johnny Cash or other celebrities, it is the inevitable cycle.

But if you used it at lesser doses, it certainly can actually improve dopamine-producing activity, but use it to get high all the time and you are caught in a loop that is very very difficult to break. The good news is that your brain can literally repair any kind of damage to these neuro-transmitters and receivers, but it takes time, and it is very hard to not relapse during this time period.

My only response to this post

 

[Zeds(NCO2CH2CH3)2]

Psychedelic wizard this is advanced drug discussion not pseudo scientifical fifth dimensional garbage discussion.
If you don't have studies to Cite or if you don't demonstrate knowledge on a given matter then either ask questions or don't post!

All of the things you have said, especially in your previous picked thread are 95% wrong pseudoscientific bs, honestly I wish I knew how much lsd or whatever you were taking daily so that I could understand you...

One thing you keep saying is we don't have sophisticated technology. Do you even know what an NMR is or a PET scan w radiolabel or an FMRI.?

The brain doesn't stop producing dopamine ever that absolute phrase is ridiculous in so many ways...

If you tell me your psychedelic drug daily stack I believe we can help each other become one of two things :
1.5th dimensional comrades with tin foil hats
2. Warlock night elf paladin druids with lv 99 insanity.

Thank you for your considerationz

 

[motiv311]

Actually it is that simple. When you pump the brain full of dopamine, it stops producing dopamine naturally anymore. I don't really see how this is a hard concept to grasp.

The brain produces a chemical based on external stimuli, thought, however it works, but seems people do not produce enough, which it then corrects.

But if you start using a high dose regularly, far beyond what is therapeutic, the brain simply stops producing as much dopamine, and the receptors do get damaged by that kind of activity.

Need proof? Find someone who has never touched amphetamine and measure their brain activity when they are doing something that is not rewarding, and again when they are doing a rewarding activity. Now get them 10 years later after chronic heavy abuse and do the same type of experiment.

All of psychiatry and neuro-science depends on anecdotal evidence, because we don't have sophisticated enough technology to conduct proper experiments yet.

Neuro-science is a very new field that barely has any real data on anything. But I am a chronic heavy stimulant user, and I know that I have tried stopping for a few weeks, and my baseline happiness while not using is much lower than before I started, but while using, it is much higher.

If you need more proof, just look at Johnny Cash or other celebrities, it is the inevitable cycle.

But if you used it at lesser doses, it certainly can actually improve dopamine-producing activity, but use it to get high all the time and you are caught in a loop that is very very difficult to break. The good news is that your brain can literally repair any kind of damage to these neuro-transmitters and receivers, but it takes time, and it is very hard to not relapse during this time period.

Ok ^ he is clearly 100 percent right... I've been on adderall since i was 11 , and i have been through everything amphetamine related.... You guys can nerd out all day long, and i can talk pharma real good to with yall... but facts is facts. TINSTAAFL .... Whatever goes up must come down.... Its pretty basic shit after all, no fancy nuero crap your 19 year old ass "unveiled" - is going to change any of that

 

[Epsilon Alpha]

Bit of a necrobump I know, but here's a really good recent review paper on our current understanding of the epigenetic effects of (meth)amphetamine in rodents.
http://www.ncbi.nlm.nih.gov/pubmed/26023847

Its interesting that HDAC1/2 appears to be central in amphetamine response and how valproate is a somewhat selective inhibitor of class 1 HDAC's as well as selectively induces degradation of HDAC2.
https://en.wikipedia.org/wiki/Histone_deacetylase#HDAC_super_family
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC165640/

Also kind of explains its fetus wreaking abilities...

TL;DR: antimanic drugs seem promising in preventing some issues associated with amphetamine use in rodents

 

[Seppi]

Bit of a necrobump I know, but here's a really good recent review paper on our current understanding of the epigenetic effects of (meth)amphetamine in rodents.
http://www.ncbi.nlm.nih.gov/pubmed/26023847

Its interesting that HDAC1/2 appears to be central in amphetamine response and how valproate is a somewhat selective inhibitor of class 1 HDAC's as well as selectively induces degradation of HDAC2.
https://en.wikipedia.org/wiki/Histone_deacetylase#HDAC_super_family
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC165640/

Also kind of explains its fetus wreaking abilities...

TL;DR: antimanic drugs seem promising in preventing some issues associated with amphetamine use in rodents

Any class I HDAC (HDACs 1, 2, 3, and 8 ) or even just a selective HDAC1 inhibitor will attenuate drug seeking behavior in rodents, not just for amphetamine either. It's still preclinical research at this point, but the way it appears to work is by inducing accumbal G9a after chronic use, which in turn opposes deltaFosB accumulation/function in nonhuman animals (see the third paragraph under this section link). Might be worth noting that the HDAC response covered in reviews on this is specific to dopamine neuronal outputs in the dorsal/ventral striatum.

 

[Razzic]

Hey guys. I'm struggling. I take dex for my inattentive type of ADD and scared to be honest (badly) of neurotoxicity and other possible effects (increase likelihood of parkinson's, irreversible damage to receptors etc)

I've read through SO many sites, SO many threads but there is not a solid list of supplements in a great format (ie just a list, which I did see but then things are discussed to take out because it is iffy and other things added and the list isn't updated) to take to stop / reverse damage, and when to take them (in the morning with dex or after you are done for the day or only on weekends ie rest days)

I've been at this for months!

At the moment I take in the morning with the dex

Green Tea
Pure EPA
Vitamin D3
PQQ
CoQ10
Hupa A
Choline
Bacopa
Gingko
Magnesium
Alpha Lipoic Acid
Curcimin (one that can cross the BBB)
Rhodiola
Resveratrol

After Dex (approx 30 min) I take some TMG to help convert any unwanted homocysteine (a damaging amino acid) into a friendlier amino acid, methionine.

In the afternoon I take ALA again
and a multivitamin (as the vit c secrets the dex if taken earlier)
along with another Rhodiola and an Ashwagandha (as previously I've suffered from anxiety and these two have helped a lot along with Inositol which I take 8g twice daily, morning and night)
Also L-Tyrosine and or L-Phenylalanine. I've also started taking this prior with good results as I read somewhere and some study that helped prevent something. Here it is http://www.ncbi.nlm.nih.gov/pubmed/10987845 But that is with D-Phenylalanine (so might take a look at getting some) but taking L side for now as it helps with restocking what the dex has depleted anyhow.

The knowledge blows me away, (as does all the reading and gets me confused some what) and whilst I have just finished biochem it is only one subject for one term at uni, I already have a greater understanding about things about nothing compared to what you guys have. Any help would be beyond helpful.

Plus might be good to update the thread?

Oh PS I also take Sodium Butyrate at night (due to http://www.ncbi.nlm.nih.gov/pubmed/23411414
"The results showed that SB reversed and prevented d-AMPH-induced behavioral effects. The d-AMPH administration induced oxidative damage in all brain structures analyzed. Depending on the cerebral area and technique, SB was able to reverse this impairment." )

Also forgot Skullcap. As I read the flavonoids help stop damage done by amphetamine.

 

[nintey]

I would be cautious of the Hup-a, ginko, rhodiola and bacopa. The rest seem safe to me

 

[Razzic]

I would be cautious of the Hup-a, ginko, rhodiola and bacopa. The rest seem safe to me

Awesome thanks for that

Any reason behind that / those?

And do you mean only taking it at the same time, afterwards or on days off should be fine?

Was staking it behind I found my memory was getting pretty piss poor and anxiety which rhodiola helped a lot with was great. But if there is solid reasons behind them and or timing just needs to be adjusted all good.

I have been taking it in that combo for about 3 or 4 years now with no unforeseen side effects but yeah still happy to take advice

 

[Epsilon Alpha]

Hey guys. I'm struggling. I take dex for my inattentive type of ADD and scared to be honest (badly) of neurotoxicity and other possible effects (increase likelihood of parkinson's, irreversible damage to receptors etc)

I've read through SO many sites, SO many threads but there is not a solid list of supplements in a great format (ie just a list, which I did see but then things are discussed to take out because it is iffy and other things added and the list isn't updated) to take to stop / reverse damage, and when to take them (in the morning with dex or after you are done for the day or only on weekends ie rest days)

I've been at this for months!

At the moment I take in the morning with the dex

Green Tea
Pure EPA
Vitamin D3
PQQ
CoQ10
Hupa A
Choline
Bacopa
Gingko
Magnesium
Alpha Lipoic Acid
Curcimin (one that can cross the BBB)
Rhodiola
Resveratrol

After Dex (approx 30 min) I take some TMG to help convert any unwanted homocysteine (a damaging amino acid) into a friendlier amino acid, methionine.

In the afternoon I take ALA again
and a multivitamin (as the vit c secrets the dex if taken earlier)
along with another Rhodiola and an Ashwagandha (as previously I've suffered from anxiety and these two have helped a lot along with Inositol which I take 8g twice daily, morning and night)
Also L-Tyrosine and or L-Phenylalanine. I've also started taking this prior with good results as I read somewhere and some study that helped prevent something. Here it is http://www.ncbi.nlm.nih.gov/pubmed/10987845 But that is with D-Phenylalanine (so might take a look at getting some) but taking L side for now as it helps with restocking what the dex has depleted anyhow.

The knowledge blows me away, (as does all the reading and gets me confused some what) and whilst I have just finished biochem it is only one subject for one term at uni, I already have a greater understanding about things about nothing compared to what you guys have. Any help would be beyond helpful.

Plus might be good to update the thread?

Oh PS I also take Sodium Butyrate at night (due to http://www.ncbi.nlm.nih.gov/pubmed/23411414
"The results showed that SB reversed and prevented d-AMPH-induced behavioral effects. The d-AMPH administration induced oxidative damage in all brain structures analyzed. Depending on the cerebral area and technique, SB was able to reverse this impairment." )

Also forgot Skullcap. As I read the flavonoids help stop damage done by amphetamine.

Hey,

So I'm not as caught up on the current state of research as I've been in the past, but here's what I would suggest. I'm in favor of taking the fewest possible things to reduce the risks of interactions and adverse effects.

Pure EPA
Vitamin D3
PQQ
CoQ10
Magnesium
Alpha Lipoic Acid
Curcimin (one that can cross the BBB)

These are the only ones I'm comfortable suggesting. In all honesty diet plays a far larger role in this that we give it credit for, keep a food journal for a week and compare it to the Canada food guide. If there is one thing I have noticed in clinic with the amphetamine using population as a whole is that a massive portion of the subjective tolerance can be related to a decline in diet quality and/or quantity.

Sorry for the brief response, Christmas is crazy.

 

[dopamimetic]

Just have to say here that I found the nootropic antioxidant emoxypine to work very well against dopamine oxidation and depletion. At least with the -phenidates, haven't tried it yet with an amphetamine but there's a good possibility for it to work too.

In one of the studies about it they also found that it raises dopamine concentration, so it makes sense.

 

[Razzic]

Hey,

So I'm not as caught up on the current state of research as I've been in the past, but here's what I would suggest. I'm in favor of taking the fewest possible things to reduce the risks of interactions and adverse effects.



These are the only ones I'm comfortable suggesting. In all honesty diet plays a far larger role in this that we give it credit for, keep a food journal for a week and compare it to the Canada food guide. If there is one thing I have noticed in clinic with the amphetamine using population as a whole is that a massive portion of the subjective tolerance can be related to a decline in diet quality and/or quantity.

Sorry for the brief response, Christmas is crazy.

Fantastic, thanks a lot. Hope you had a good Christmas.

Would the others be safe to say take it after dex (coming down) or on rest days you think?

 

[Razzic]

Just have to say here that I found the nootropic antioxidant emoxypine to work very well against dopamine oxidation and depletion. At least with the -phenidates, haven't tried it yet with an amphetamine but there's a good possibility for it to work too.

In one of the studies about it they also found that it raises dopamine concentration, so it makes sense.

Interesting, I've read it helps repair damage from alcohol also, although I'm not so sure those studies didn't need further studies to confirm this, sounds promising though. I take Immune Renew from NOW as I was buying Cordyceps (for adrenal fatigue from the dex) and Lion's mane (to repair damage done from dex also) but was working out really expensive. Not sure if it helps as much but it is a lot cheaper. Also claims to protect cells. Partner got sick and was 24/7 around me, another person then got sick she is rarely around and I'm still yet to get it, another bonus.

 

[dopamimetic]

All these studies aren't quite as reliable as they should be, that's what I do think today. We have too many conflicting findings, flawed animal experiments etc. and this is only what has been published (a huge part doesn't become public). But it's the best we have. This, and the endless reports on the internet - out of which I am making my own theories, and post them ... so others can think about them, show me faults or that I'm right, and continue ... this is the only and best way to achieve something

But yes, emoxypine could be helpful when drinking too - just that you have to take it repeatedly, as long as you have alcohol or it's metabolites in your system. The same for the stimulants. 125mg's of emoxpine with the first dose, and then again every 3-4 hours.

 

[Razzic]

One thing that is very concerning is the permanent down regulation (or I should say stoppage) of the D1 dopamine receptors in the prefrontal cortex. These are used for memory and learning and anything above even a very low therapeutic dose will turn those off and enable D2 receptors instead. These act very differently and it is only really what the recreational guys would be seeking, not those hoping to solve ADD issues.

These do not come back on. Even after years off Dex which is very concerning and would very much be the reason why you can never concentrate properly while off of it even worse than when you first began. D1 receptors DO come back on in other parts of the brain after a break though (which is still why you would feel better after taking a break and get some benefit) but the prefrontal cortex is where your learning and short term memory etc is all from, specifically your D1 dopamine receptors are a major part of this whole process.

I'm really concerned about this and hoping to find supplements or some other way of reversing this. This would not be an issue I guess with people on Memantine protecting themselves but being in Australia my Psychiatrist will not even look at that being for Alzheimer's only. It has also become obvious I now know more than my Psychiatrist in the way of a lot of things, especially after going to university it is scary. Any time I ask about metabolism of drugs (specifically the ones he is prescribing me) he has no idea. Or the pathways etc. I've found this with numerous GP's and Psychiatrists and they admit they just rely on being advised from someone in their yearly meetings about such things, which never happens (or very rarely at best)

So any help with be fantastic. Supplements have saved me many times (had major depression and they fixed it over normal antidepressants in the past) but only were mediocre with ADD, got about 25 - 30% benefit at best. But I really need to fix this problem with the D1 prefrontal cortex dopamine receptor problem.

 

[Seppi]

These are used for memory and learning and anything above even a very low therapeutic dose will turn those off and enable D2 receptors instead.

Amphetamine doesn't work that way; amph releases dopamine in the PFC which then binds to any available DA receptors. Amphetamine can modulate neuronal firing, but this mechanism is independent of dopamine receptor activity.

but the prefrontal cortex is where your learning and short term memory etc is all from, specifically your D1 dopamine receptors are a major part of this whole process.

The PFC is primarily responsible for the "cognitive control" of behavior (aka executive functions), although it does play a lesser role in countless other cognitive processes (e.g., see the aptly titled review "What the orbitofrontal cortex does not do"). The only form of memory which the PFC is largely responsible for is working memory (a component of cognitive control). That said, D1 receptors in the PFC do play a significant role in cognition since they positively modulate these cognitive functions.

So any help with be fantastic.

Consistent aerobic exercise affects the structure and interconnectivity of the PFC; it also improves cognitive control. These structural and functional improvements are permanent, but occur gradually (i.e., measurable changes occur on the order of weeks to months). See https://en.wikipedia.org/wiki/Neurobiological_effects_of_physical_exercise#Structural_growth for more info.