Amphetamine Neurotoxicity and Tolerance Reduction/Prevention

[Epsilon Alpha]

Hello, I'm Delta Gamma from Imminst, a while back I made a thread about preventing some of the negative consequences of amphetamine use particularly at AD(H)D dosage patterns which can be found via the link below. I believe that this information may be more appreciated by this audience.

NOTE: I am not a medical doctor, take everything I say with a grain of salt.

http://www.longecity.org/forum/topic/47231-amphetamine-neurotoxicity-reductionprevention/


Now for possible methods for reducing tolerance that I haven't mentioned in the above thread:

VMAT2:
Its pretty much a fact that amphetamine massively down regulates VMAT2 which has all sorts of effects from Parkinson's disease to depression, both which have been shown to occur at alarming rates in amphetamine users. With that said, lithium has been shown to up-regulate VMAT2 as well as D2/D3 autoreceptors (which are important in combating dopamine dysregulation). There is also reason to believe that increased VMAT2 could help prevent amphetamine induced neurotoxicity, though much of the research I'm quoting used rat studies.

http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2000.0742217.x/full
doi:10.1016/S0006-8993(02)03284-5
http://www.neuropeptidesjournal.com/article/S0143-4179(08)00051-6/abstract
doi:10.1016/j.pbb.2007.10.013
http://www.fasebj.org/content/14/15/2459.full

Tyrosine and Tryptophan Hydroxylase:
Methamphatamine has been shown to result in decreases in the activity of both tyrosine and tryptophan hydroxylase, which may be one of the reasons for acute to long term tolerance. Some studies have shown SSRI's and melatonin to help prevent meth induced decreases in the activity of these enzymes. There is also the issue of reduced tyrosine hydroxylase expression in at least cases of massive abuse, which goes into genetics that I won't discuss in the OP, but suffice to say that melatonin may prevent/reverse amphetamine's effects on tyrosine hydroxylase expression though I haven't worked out the dosages or if the effect carries over to humans.

http://jpet.aspetjournals.org/content/214/2/257.short
http://jpet.aspetjournals.org/content/286/2/1074.full
http://www.fasebj.org/content/17/13/1775.full
http://www.ncbi.nlm.nih.gov/pubmed/19409439
doi:10.1016/j.neulet.2008.03.053

I'll get more into it later when I don't have a playful dog tugging at my sock.
Any contributions will be appreciated

Mods do with this what you will.

 

[[skrillex]]]

nice i really like the first link.

you might wanna add something about using methylcobalamin, in one of my books it talks about how it can help prevent/reduce the risk of parkinson's. and i believe it induces neurogenisis at higher levels.

 

[Epsilon Alpha]

nice i really like the first link.

you might wanna add something about using methylcobalamin, in one of my books it talks about how it can help prevent/reduce the risk of parkinson's. and i believe it induces neurogenisis at higher levels.

You're right about this form of B12, it does show more promise in preventing Parkinson's than the cyanocobalamin which is found in most multivitamins. Unfortunately, I believe that it would be one of the "key" supplements for the prevention of neurotoxicity beyond adequate levels, though I might be missing some info.
http://www.jns-journal.com/article/S0022-510X(07)00054-8/abstract
It does have a lot to do with neurodegeneration in older people (who are generally B12 deficient), but I couldn't find anything about neurogenesis with a quick google search. If you could post anything relating it to neurogenesis that would be great

- ~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.

PQQ and very low dose lithium seem promising and I will add on them as I learn about their implications. MAO-B inhibitors may potentate amphetamines and reduce harm, but I would not recommend their use to anyone outside a medical setting.

The above recommendations are mainly for AD(H)D treatment usage patterns, so they may have to be adjusted for abuse/recreational use.

Do you guys think I should do a intro to the mechanisms of amphetamine neurotoxicity?

 

[DrunkardsDream]

Take low doses of Dexedrine or Adderall and AVOID meth and high doses of said prescription amphetamines.

Also don't let yourself get dehydrated-drink water, and force yourself to eat food.

 

[nj754]

Resveratrol looks like it might prevent the neurotoxicity. It's an antioxidant and has some other properties that may make it neuroprotective.

 

[rakketakke]

Lovely

First link is very useful!

 

[Epsilon Alpha]

Resveratrol looks like it might prevent the neurotoxicity. It's an antioxidant and has some other properties that may make it neuroprotective.

It does have some properties that would make it seem like a promising candidate: apoptosis inhibitor, mitochondrial support, and antioxidant among other things. However, my main concern isn't that it wouldn't work but rather its half life in the body. If you could work a way around that it would be a stellar substance though.

It would also deal with nNOS and possibly iNOS activation in the brain, which produces reactive nitrogen species (RNS). Currently I'm having trouble looking for specific inhibitors or RNS scavengers which are safe and easily available, but it does seem that dark fruits and vegetables would exert some sort of protective effect by this pathway.

However, PQQ does seem to act as effective RNS scavenger with a decent amount of safety data behind it. It also seems that it upregulates several aspects of cell metabolism (something that amphetamine kind of rapes), though its activation of CREB may induce a slightly faster tolerance build up to some of amphetamines effects. The last bit is conjecture on my part. However, the anecdotal reports in the first thread were very promising.

Lithium seems to have a effect in the NMDA/NOS pathway as well, but seeing as my journal access is cut off during the summer I can't go much more into it. But, it had a rave review by a fairly knowledgeable poster.

EDIT: forgot to add that NMDA antagonists do have some proven efficacy in tolerance prevention and in dealing with neurotoxicity. But, we've already got a thread going on that so I'll stick to other topics suffice to say majorly altering your ion balance and getting massive intracellular concentrations of free Ca2+ is bad mmmkay?

 

[Epsilon Alpha]

Curcumin: or how yellow dye E100 saved my genes

Curcumin is probably the single most promising compound I have found as far as amphetamine tolerance and toxicity goes. On the tolerance prevention side of things it inhibits CREB, which is one of the major pathways for tolerance to many drugs, through a possibly downstream mechanism from that it acts on histone acetylation (which may also be due to its potent antioxidant effects). What this means: curcumin has been shown to inhibit some of the pathways involved in changes in gene expression, which has potentially massive implication as far as tolerance development goes.

doi:10.1016/j.brainres.2006.09.009
doi:10.1016/j.bcp.2005.01.014
http://www.jneurosci.org/content/14/9/5623.full.pdf
http://www.cell.com/neuron/abstract/0896-6273(95)90225-2

Now for its antioxidant goodness: curcumin has been shown to protect against 6HODA induced Parkinson's in rats and has a very potent antioxidant effect. Antioxidants have generally shown a protective effect in amphetamine neurotoxicity.

doi:10.1016/j.brainres.2010.10.023
http://www.springerlink.com/content/n6280l8h17282630/
doi:10.1016/j.cbi.2008.05.003

It also has a ludicrous amount of other effects such as MAO inhibition, iron chelator, stimulator of trophic factors and others I discussed in the earlier thread.

Its also proven to be safe at dosages up to 10g a day in cancer studies.

 

[Fyasko.]

yeah curcumin increases BDNF levels.

would it be okay if i just went to the store and picked up a bottle of the actual spice and just put it in gel capsules? it seems like it'd be much cheaper that way.

and what doses would you recommend? for days on and off amphetamines.

 

[Epsilon Alpha]

yeah curcumin increases BDNF levels.

would it be okay if i just went to the store and picked up a bottle of the actual spice and just put it in gel capsules? it seems like it'd be much cheaper that way.

and what doses would you recommend? for days on and off amphetamines.

The spice itself only contains ~5% curcumin so I'd definitely go with the capsules. As far as doses go, the average Indian consumes about 200mg curcumin a day so I'd start there if you're sure you've got a bioavailable formulation.

I really can't give a "abuse" level dosage as I'm not comfortable recommending people to consume over a gram of a (weak) non-selective MAO inhibitor then binging. If you slowly increase your dose from 200mg you'll probably know when you hit your body's sweet spot.

 

[Fyasko.]

^alright. ill go pick up a jar of curcumin (the capsuled stuff) soon.
do i need to use it the week of amphetamine use or can i use it only on the day of?

 

[Epsilon Alpha]

If someone with bluelighter status could send this message to "Altered Perception" that would be great.

Hello,

I'm currently compiling evidence on how amphetamines and their derivatives can affect gene expression and was wondering if you had any specifics from your case. I'm currently working on my BSc honours pharmacology, and I'm hoping to gather some evidence on the topic so that one of the profs in my department will throw me some expertise on the topic.

If you could share some of the details on your condition I think it could help point me in the right direction for further research into amphetamines and gene expression.

Thanks
-Epsilon Alpha

 

[specialspack]

T
I really can't give a "abuse" level dosage as I'm not comfortable recommending people to consume over a gram of a (weak) non-selective MAO inhibitor then binging. If you slowly increase your dose from 200mg you'll probably know when you hit your body's sweet spot.

A weak MAOI as in it would be safe to predose before recreational d-amp/methamphetamine?

 

[Epsilon Alpha]

A weak MAOI as in it would be safe to predose before recreational d-amp/methamphetamine?

Yeah, its very weak but I would rather err on the side of caution. I think 200-500mg should be a good starting range if you do plan on using it with recreational doses but this stuff on paper looks like it would potentate amphetamine. With that said it would probably best to test it out with a very low dose of amphetamine and see what happens.

Also, it seems like it should be taken 2-4 hours before amphetamine with food from some of the discussion on Mind and Muscle.

I'm not a doctor so I can't guarentee everything I say here applies perfectly to the real world, but its where the research I've read points me.

 

[Fyasko.]

If someone with bluelighter status could send this message to "Altered Perception" that would be great.

alright i sent it to him, just because of how helpful you're being:D

 

[Epsilon Alpha]

Does anyone know if there would be an interaction with taking adderall during the day and at night when the medication wears off supplementing:

-spoonful of curcumin, spoon tip of pepper, spoonful cayenne pepper dunked into coconut milk and then chugged gruesomely. (is this efficient/effective?)
-100mg trans- reservertrol
-1 gram of cat's claw root (said to be a weak maoi?)
- 400 mg magnesium citrate
-10-20 mg memantine (after titrating)
-400mg of L-Theanine
-5mg lithium orotate
-100mg na-rala
-260mg of actual dmae
-foodbased multivitamin

do you guys think this cocktail = good combination for lowering tolerance/ preventing damage? Does any of the dosage need adjusting?

I realize this is advanced drug discussion, and advanced I am not. Based on my reading and reading, this is what I have procured.

I also take other adaptogens: ashwaganda, bacopa, lion's maine, etc but am more unsure of those then the supplements listed.

-DMAE isn't something I would supplement mainly because there isn't strong evidence it does much.
-Na-RLA is probably a good thing but the dosage might be a little high(depends on your chemistry)
-I'd start at 1 or 2.5mg lithium just because of J.Galt's mention of a steep dose response curve.
-Resteverol is generally a benign compound so it should be fine.

-I'd just have some curry for breakfast rather than chugging that compound, a lot of the ingredients are the same and it seems far more palatable haha, curcumin seems like it should be taken in the morning with food from my understanding.

-Memantine seems fairly promising, but I'd only suggest it if you could get a script (however if we're talking about amphetamine abuse here I'd say it could be beneficial, extended release DXM has shown some of the same promise as well).

-Cat's claw should be something you slowly titrate after starting curcumin as too much MAO inhibition kind of equals bad.

-The magnesium citrate is a good choice and dosage, though perhaps taking it in two doses with meals would be better.

- Theanine I really don't know much about, as well as the other adaptogens (save bacopa) so perhaps adding them in as temporary additions to see if they do anything subjective could lead to some interesting info.

But, are we talking about abuse or AD(H)D dosages here? It kind of changes what you should do and when.

My personal suggestion is to add in some melatonin at night as well simply as a precaution and maybe some CoQ10.

 

[MeDieViL]

Interesting thread, keep up the good work.

 

[Epsilon Alpha]

I just wish I could get fairly close to being inbetween buzzed and drunk without blacking out. I always black out. Adderall saved me from that and made it impossible, no matter how much I drank. I can easily say, without a doubt, if I didn't get an adderall script when I did I would have been dead by now. No lie. So whatever adderall might do to my system: premature aging, balding, lower testosterone, etc doesn't really matter as I wouldn't still be here without it.

Maybe drinking just isn't for you then, but I do know the temptation in college especially in the states.

As far as the supplements go, try to be aware of possible interactions especially with adaptogens. But, if I had to give a daily essentials list for amphetamine users at below binge doses it would be this: a multivitamin, CoQ10, magnesium, and melatonin.

Of course a responsible lifestyle plays a big role as well.

 

[bben]

Maybe drinking just isn't for you then, but I do know the temptation in college especially in the states.

As far as the supplements go, try to be aware of possible interactions especially with adaptogens. But, if I had to give a daily essentials list for amphetamine users at below binge doses it would be this: curcumin, a multivitamin, CoQ10, magnesium, and melatonin.

Of course a responsible lifestyle plays a big role as well.

I would add NAC to that, it attenuates methamp damage in some models.

 

[Fyasko.]

Maybe drinking just isn't for you then, but I do know the temptation in college especially in the states.

As far as the supplements go, try to be aware of possible interactions especially with adaptogens. But, if I had to give a daily essentials list for amphetamine users at below binge doses it would be this: curcumin, a multivitamin, CoQ10, magnesium, and melatonin.

Of course a responsible lifestyle plays a big role as well.

i think imma go with this, the product that i want is curcumin+bromelain, thats good right?8)

im gonna switch out CoQ10 for fish oil,
and maybe add some tyrosine in the mix.

are we talkin magnesium taurate or any kind?