Reducing stim (adderall) neurotoxicity/dopamine depletion+MAOIs

[smokester]

See if you follow me and then add your observations:

So amph is a great AD, and I use it in the form of Adderall 30 mg XR, though it inevitably being neurotoxic and coming with a crash (though nowhere near an XTC or meth crash).

Now some of speed's pluses vs. XTC in their neorotoxic roles on the dopaminergic and serotonergic systems, respectfully.

-Since XTC isnt an MAOI inhibitor (like amph), it totally flushes your serotonin, which subsequently is simply oxidized by MAO and depleted, hence the quick loss of magic for at least two weeks (though 1 month is optimal), preceeded of course by a massive crash.

-NOW speed, OTH, is also an MAO, besides a dopamine releaser and reuptake inhibitor, allowing for lots of dopamine to be recycled by DTs. This is pretty obvious in "meth binging", where even massive loads of super-strong meth maintain their (dopaminergic) effects for days, however less and less euphorically- with a CRASH coming at the end.

So we know that amph is neurotoxic, which can be counteracted with oxidants (for me: q-10, 1 g vit c, ginkgo, red grapes+seeds, vit e, or melatonin/5-HTP); my question is: how should they be taken for maximal optimization of neuroprotective effects, given their half-lives, lipid solubility, etc? Remember it's XR, and I have no idea whatsoever when the neurotoxicity is at its most violent (the amph itself or its or dopamine's metabolites).

However, the problem of the amph crash for at least a day or two remains- until the portion of depleted dopamine ("zapped" or MAOIzed) that wasnt recycled is resynthesized.
So- let's brainstorm some options of preventing, the excessive MAOxidation from happening, as the simultaneous DT reuptake and MAO inhibition is weaning with plasma/synaptic levels of amph decreasing, and a stressful, toxic environment for all that synaptic dopamine waiting to be sucked up radically increases, along with its icky hydrogen peroxide metabolites...

1) Pharmaceutical MAOIs to take over amph's attentuating inhibition of the dopamine-destroying, peroxide-producing enzymes.

E-x. I have the rMAOI (80 % -A, 30 % -B) moclobemide (Aurorix) at my disposal, which reportedly equally inhibits dopamine MAO, whether A or B, which is supposedly non-selective come DA breakdown (whereas serotonin is deaminated by the MAO-A subtype, hence moclobemide's theoretical greater utility with MDMA).
-Do you find it feasible to minimize amph's crash+neurotoxicity utilizing a MAOI, and does anybody have some input regarding moclobemide/Aurorix//other MAOIs (A/B) and its/their role in dopamine-specific pharmacology, ie. dopamine salvation?
-So far I took 150 mg MB (starting dose) with my 30 mg XR capsule in the morning, and as of T+6 am experiencing a minor, albeit definitely attentuated, comedown (not crash). Tomorrow I will reasses my DA assets, as Im still in an afterglow, and accordingly try 300 mg divided at T+2 h and t+5 and see if my head feels ravaged.

Together, hopefully, we may tackle and eliminate the mechanism behind the neurotoxicaly affected , DA-depleted brain and its response- the crash, and, in the longer term, cognitive impairment, through MAO/neurotoxically induced dopamine deficiency and dopaminergic degeneration.

...the end.


PS What are the best dopamine precursors, besides broad beans and rx'd L-DOPA, to replenish the unlucky DA that will always be lost, right up until our senior (hopefully not senile!) years, a process chronic stim use only precipitates (though were trying to attentuate it)?

Peace.

 

[hussness]

I might be wrong about this, but I was under the impression using any MAOI with a less than miniscule amount of amphetamine posed a significant chance of death. I would be a little more worried about that an long-term neurotoxicity.

 

[Crimethink]

I know your unit dose (30mg) - is that all you take per day? I ask b/c you mention crashing & I didn't know it was common at the 30mg XR point - plus the body/brain can deal with a seemingly large single dose of Amp. w/ nil neurotoxicity - divide that same dose up as if you were smoking it outa a pipe throughout the day and it's way worse.

As for dopamine depletion - it doesn't have to happen to nearly the same extent with the antioxidant protection you mentioned. MAO inhibitors seem to play a less important role here. Esterified vitamin C is good esp b/c it comes with citrus bioflavonoids, as for vitamin E get the variety with all 8 forms of E - Alpha, Beta, Gamma, Delta - Tocopherol/Tocotrienol.

If you look at the pharmaceutical circular / monograph for Adderall near the end you'll see teratogenicity...mutagenicity - underwhich you'll see the (Bruce) Ames Salmonella assay for mutagenesis - the gold standard. Anyway, Bruce thinks everyone should take acetyl-Lcarnitine and (R)-alpha lipoic acid and so do I. They quench all kinds of radicals, stabilize cell membranes, improve functioning of mitochondria and slow one of 6 aspects of aging.

I suggest you take your antioxidants 45 mins before the adderall. If any of them have really short half lives you may need to re-dose. The stress of amphetamine follows a complex and variable time course for perhaps up to 48 hours after admin. (This probably is more signifigant for higher doses)

Most amphetamine neurotoxicity is mediated inside the cell by DA-Quinones and hydroxyl radicals. (This should help you in selecting antioxidants too - Brain penetrant, cell membrane/mitochondrial penetrant, fat and water soluble, cover different radicals - but you've allready got some great ones that qualify.)

As for Dopamine... about all I can recommend is Acetyl-L-Tyrosine & phenylalanine - with BH4/Tetrahydrobiopterin is way better. Maybe someone who knows chemistry can tell you if those blue artifical sweeteners will work as a source for phenylalanine (you may get aspartate and a drop of methanol too.)

 

[theWorldWithin]

Honestly I think taking an MAOI with amphetamine is really not in the interest of harm reduction. You may have some short term theoretical protection but no one knows the long term effects of MAOI use. In my opinion its quite a sketchy proposition and can get you into some serious trouble. What if you pin down a safe MAOI/AMp combo then eat a food that is contraindicted without knowing it? You are fucked! Its not worth the risk in my opinion.

Chronic use of MAOI's may (and more than likely do) present their own set of serious risks.

 

[MeDieViL]

I might be wrong about this, but I was under the impression using any MAOI with a less than miniscule amount of amphetamine posed a significant chance of death. I would be a little more worried about that an long-term neurotoxicity.

there is no evidence for that combination being dangerous, and both can be used safely

 

[vecktor]

DO NOT MIX AMPHETAMINE WITH CERTAIN MAOI'S
the combination of adderall for example and MAOI's is contraindicated for 14 days after the cessation of maoi use as hypertensive crisis can arise. due to the enhanced pressor action of amphetamine.

subtype selective maoi's like moclobemide and amphetamines might be possible but this is dangerous territory and certainly not one to explore without proper medical guidance and support.

 

[fastandbulbous]

there is no evidence for that combination being dangerous, and both can be used safely

What! There are plenty of documented reports of the interaction of amphetamine & relatives (phentermine etc) with MAOI causing severe , sometimes fatal, hypertensive crisis. Although that was mainly with the non-competetive (irreverisible) inhibitors such as phenelzine, potent reversible(competetive) inhibitors like harmala alkaloids can cause potentially life threatening situations to occur.

This really seems, in terms of harm reduction, a case of 2 steps forward & 3 steps back

 

[zrawdog]

DO NOT MIX AMPHETAMINE WITH CERTAIN MAOI'S
the combination of adderall for example and MAOI's is contraindicated for 14 days after the cessation of maoi use as hypertensive crisis can arise. due to the enhanced pressor action of amphetamine.

subtype selective maoi's like moclobemide and amphetamines might be possible but this is dangerous territory and certainly not one to explore without proper medical guidance and support.

what about st john's wort? is it strong enough to be dangerous as well?

 

[theWorldWithin]

^That all depends upon your dosage of amphetamine and St Johns Wort, but really is it even at all worth it?

Just take your ALA and multi vitamin if you are worried about neurotoxicity. I would not want to be on any MAOI long term anyway. And if you are thinking about using them for single high dose amp protection then you are in major trouble.

 

[Hammilton]

I assume that selegiline would be safer at <10mg doses, since MAO-A does everything MAO-B can do, right? MAO-A will be able to catch up with the increased monoamine levels, it'll just take a while.

If my thinking is right, this explains why selegiline+phenethylamine produces a short lived, instead of long term stimulation, correct?

 

[The Monkey Mantra]

As a merely anecdotal report: Selegiline has, in the collective experience of a group of friends and I, an attenuating effect on both central and peripheral effects of amphetamine and methamphetamine. I've tried it with both desoxyn and dexedrine at sensible doses of each (10 and 10).

This monkey found it to be safe, with little evidence of change in effects except for a noted dulling of euphoria and stimulation, as noted. It had a reputation around the circles I ran in as having a lengthening but peak-reducing effect on MDMA, too. Smoother comedown, minimal hangover. Never tried it myself, as I've never really been into MDMA other than a few odd trial runs.

I'm also gonna have to say, as I believe I said in another thread, that selegiline had an extraordinary effect on 2c-t-2, increasing central effects to an *amazing* degree (something like 5x or more, I'd say) while reducing peripheral effects. Or, rather, really changing the ratio of central to peripheral effects and producing an incredible afterglow. Please don't try it at home. I'd been taking selegiline for about a week at like 10 mg of liquid a day. My friend had 10 mg just that day and didn't get much effect. If by some chance you're dumb enough to follow my lead, don't exceed about 3 mg of 2c-t-2 the first time.

Sorry for that aside!

 

[Hammilton]

Holy shit, you're combining MAO-A inhibiting doses of selegiline with MDMA? That's a recipe for disaster.

 

[The Monkey Mantra]

They all seemed to like it. Lots of samples, too! Probably 50 trials in a population of, oh, 20? Again, I never tried it, but there were no problems reported.

 

[Hammilton]

I was thinking about this today. What about using nepicastat (sp?) a dopamine hydroxylase inhibitor. With primary releasers, would this prevent major declines in dopamine levels?

If nothing, it ought to reduce peripheral effects.

I don't know much about the drug beyond that.

 

[The Monkey Mantra]

Disulfiram is the classical (and much more easily available) DBH inhibitor. It does a bunch of weird things with cocaine:

First, it makes ya more sensitive to the psychomotor effects. That's *not* a good thing.

Second, it makes you more sensitive to the rewarding effects.

Third? More sensitive to the aversive effects.

https://etd.library.emory.edu/view/record/pid/emory:16nrf
It should be mentioned that Disulfiram is undergoing study for cocaine dependence.

Now for the amphetamines: First off, disulfiram is undergoing open-label studies for methamphetamine dependence. There's a study that caught my eye, though. It mentioned that disulfiram in schizophrenics markedly increased psychotic symptoms. In cats, disulfiram in combination with amphetamine was used to model these symptoms:

http://www.ncbi.nlm.nih.gov/pubmed/1241912

It also, however, enhances the subjective effects in humans, be it "high" or "anxious" or "want more" or "bad drug effect" measures. Sounds exactly like the cocaine!

Exercise caution.

 

[SpunkySkunk347]

See if you follow me and then add your observations:

So amph is a great AD, and I use it in the form of Adderall 30 mg XR, though it inevitably being neurotoxic and coming with a crash (though nowhere near an XTC or meth crash).

A speed crash can be just as bad if not tremendously worse. The reason being that there is MUCH more noradrenergic activity with Adderall, because adderall has the levo isomer of amphetamine (which is more peripheral but the small amount that does somehow manage to reach the CNS causes norepinephrine release) and also because amphetamine is less dopaminergic than meth and MDMA in nature.

Now some of speed's pluses vs. XTC in their neorotoxic roles on the dopaminergic and serotonergic systems, respectfully.

just for future reference, it is a much more understandable choice of wording if you say "MDMA" instead of "XTC" because really "XTC" is not only slang, but it is slang for an already slang word, even worse it is a nonsensical abbreviation.
Really, think about it... Methylenedioxymethamphetamine was discovered, and in human ingestion it was reported to cause "euphoria and ecstacy" -> Some druggy chemist found out how to synthesize it, then he began selling it but no one wanted to buy "Methylenedioxymethamphetamine which causes euphoria and ecstacy" because by the time he had finished pronouncing the second syllable the potential buyer had already lost interest -> The druggy chemist found it would be better to simplify "Methylenedioxymethamphetamine which causes euphoria and ecstacy" by dumping all those words and just keeping the last word "ecstacy" which not only is easier to say, but also sounds funner and sexier -> People did not know how to spell "ecstacy", so it turned into "extacy" -> Years later, with the advent of the internet, some fat drug user's fingers became tired when he had to type out "extacy", so he dropped half the letters to make it "XTC". This term quickly caught on because it looked cooler having an "x" at the begining of it, and people could when looking at the term for the first time could go "What's XTC? wait a second.... ecks.... tee..... see.. OH I C WAT U DID THAR!!!"

-Since XTC isnt an MAOI inhibitor (like amph), it totally flushes your serotonin, which subsequently is simply oxidized by MAO and depleted, hence the quick loss of magic for at least two weeks (though 1 month is optimal), preceeded of course by a massive crash.

I'm not certain, but I believe that the lack of serotonin after a single MDMA dose should last only about 2 weeks at max for a healthy individual.
Also, serotonin is not completely "flushed out". If it was, then not only would varying doses have the same effects but people would be dying left and right from serotonin syndrome.

-NOW speed, OTH, is also an MAO, besides a dopamine releaser and reuptake inhibitor, allowing for lots of dopamine to be recycled by DTs. This is pretty obvious in "meth binging", where even massive loads of super-strong meth maintain their (dopaminergic) effects for days, however less and less euphorically- with a CRASH coming at the end.

Meth shouldn't be causing significant stimulation for more than a day or two at most.

So we know that amph is neurotoxic, which can be counteracted with oxidants (for me: q-10, 1 g vit c, ginkgo, red grapes+seeds, vit e, or melatonin/5-HTP); my question is: how should they be taken for maximal optimization of neuroprotective effects, given their half-lives, lipid solubility, etc? Remember it's XR, and I have no idea whatsoever when the neurotoxicity is at its most violent (the amph itself or its or dopamine's metabolites).

ANTI-oxidants, not oxidants. I'm also fairly certain that melatonin and 5-HTp are not anti-oxidants.

1) Pharmaceutical MAOIs to take over amph's attentuating inhibition of the dopamine-destroying, peroxide-producing enzymes.
E-x. I have the rMAOI (80 % -A, 30 % -B) moclobemide (Aurorix) at my disposal, which reportedly equally inhibits dopamine MAO, whether A or B, which is supposedly non-selective come DA breakdown (whereas serotonin is deaminated by the MAO-A subtype, hence moclobemide's theoretical greater utility with MDMA).
-Do you find it feasible to minimize amph's crash+neurotoxicity utilizing a MAOI, and does anybody have some input regarding moclobemide/Aurorix//other MAOIs (A/B) and its/their role in dopamine-specific pharmacology, ie. dopamine salvation?
-So far I took 150 mg MB (starting dose) with my 30 mg XR capsule in the morning, and as of T+6 am experiencing a minor, albeit definitely attentuated, comedown (not crash). Tomorrow I will reasses my DA assets, as Im still in an afterglow, and accordingly try 300 mg divided at T+2 h and t+5 and see if my head feels ravaged.

NOW you are crossing the lines of being simply wrong to spewing out dangerous advice disguised as fact. Using an MAOI with amphetamine could easily KILL YOU. PLEASE ANYBODY READING THIS, DO NOT TAKE AMPHETAMINE OR METH WITH AN MAOI

Together, hopefully, we may tackle and eliminate the mechanism behind the neurotoxicaly affected , DA-depleted brain and its response- the crash, and, in the longer term, cognitive impairment, through MAO/neurotoxically induced dopamine deficiency and dopaminergic degeneration.

...the end.

However "in the mood to type shit" you are, it is not an excuse for you to spew out such false and dangerous "advice" in a factual tone.
You are throwing around terms very loosely, often mixing them up in the process. The crash and side effects after amphetamine are caused mostly by fatigue, not the death of brain cells via monoamine oxidase. "Neurotoxically induced dopamine deficiency and dopaminergic degeneration" does not make sense on so many levels. Just because "neurotoxicity" sounds cool, does not mean it is the most appropriate word to use.
Amphetamine is metabolised by CYP2D6, not MAO. However, dopamine is metabolized by MAO, and inhibiting MAO's action would cause a dangerous level of side effects. Even if it didn't kill you when you mixed an MAOi with amphetamine, a large portion of brain cells are more than likely dead due to your spike in body temperature.
The majority of neurotoxicity caused by amphetamine is mostly due to an increase in body temperature, and a smaller fraction of neurotoxicity is caused by oxidation.

When a moderator see this, please put a disclaimer or something at the top of this thread so some moron doesn't go out and kill himself by mixing meth and an MAOI... shit like this is bound to cause trouble if left floating around, especially since it is stated so factually as if he knows what he is talking about.

 

[SpunkySkunk347]

COME ON PEOPLE, it doesn't take more than a simple search on google to come up with numerous death reports from an MAOI-induced hypertensive crisis from mixing them with stimulants, and literally HUNDREDS of sites giving huge cautionary disclaimers saying "DO NOT TAKE AMPHETAMINE IF YOU ARE ON AN MAOI"

Since apparently the numerous warnings from countless sites was not enough, here is a picture which displays the situation:

 

[Hammilton]

You may not know this, but psychiatrists are much more commonly prescribing selegiline + stimulants today. With selegiline at sub-10mg/day doses, only MAO-B is significantly inhbited. Because dopamine may be metabolized by MAO-A, there still remains a functional metabolic route making the described issues much less likely than with something like Nardil or Parnate.

With selegiline it would seem that it can be safely done, but I would imagine that the dosing would have to be significantly reduced.

 

[filenet]

...NOW you are crossing the lines of being simply wrong to spewing out dangerous advice disguised as fact. Using an MAOI with amphetamine could easily KILL YOU. PLEASE ANYBODY READING THIS, DO NOT TAKE AMPHETAMINE OR METH WITH AN MAOI....

ahoy there Captain Generalisation! do you believe all your google search results and apply them across the board? 8)

its not uncommon for professionals to prescribe moclobemide with various stims like d-amp or mph. surely your google time told you that not all MAOIs are the same.

i've personally had no issues over the years, not even a slight rise in bp, when combining moclobemide (prescribed & non-prescribed) with d-amp, mph, d-methamp, 4mar, coke and so on...

sure there are the ones which must be avoided so perhaps google them

 

[Hammilton]

I'd definitely be mostly concerned about irreversible, nonselective MAOIs. RIMAs are unlikely to be dangerous because they don't inhibit the main pathway for DA, which is MAO-B.

I'd be mostly concerned about those that irreversibly inhibit A and B because they leave none of the intended routes for dopamine metabolism available.