• N&PD Moderators: Skorpio | thegreenhand

Amphetamine Neurotoxicity and Tolerance Reduction/Prevention III

I found that 30 milligrams of DXM, at dinner everyday stops tolerance in it's tracks. Not for meth (never tried it), but for amphetamine and Temazepam at least...

Just speaking from experience

When you are an avid meth user you only use meth all day long. You are practically always spun. There no time to take other drugs unless you want to be on it and meth.

I never felt addicted to it but it's a "I am using till it's gone" kind of drug.

Then again in 2011 I managed to have stupid amounts on hand and not use for a whole day. So I dunno. It took a stupid degree of will power.

If you're not on a "constant spun" type of meth use, and can handle infrequent usage of meth, tolerance shouldn't be a problem. The issue is so few people are able to do just that.
 
I didn't know this thread existed. I wrote a big article on this too, maybe we should merge them:
http://www.bluelight.org/vb/threads/699342-Protecting-the-brain-and-body-while-on-amphetamines
I have lots of new info since I wrote that article. Most interesting one is the properties of PQQ. It induces mitochondrial biogenesis. The mitochondria are the most susceptible to free radical attack, and damaged mitochondria is one of the main causes of aging, and I've read reports of people curing their "incurable" neuropathy by taking substances which protect and regenerate the mitochondria.

I found that 30 milligrams of DXM, at dinner everyday stops tolerance in it's tracks. Not for meth (never tried it), but for amphetamine and Temazepam at least...

Really? 30mg is a pretty low dose, do you even feel any effects from the DXM? DXM is a weird one with a complex mechanism of action, but its pretty long lasting so I'd say its a better choice than ketamine. Maybe PCP and related drugs would work better. They cause neurotoxicity of their own, and I believe this is mediated by sigma receptors so taking a mild sigma antagonist should prevent that. Also, just about all forms of drug induced neurotoxicity involve excessive influx of Ca2+ ions and calcium channel blockers are proven neuroprotectants. Vinpocetine is a calcium channel blocker and vasodilator.
 
30mg is the therapeutic dose (for coughs) of course there are effects.
I don't know what makes you think DXM is long lasting as wiki states a half-life of 3-5 hours, though the effects on the brain last longer than the DXM does I can't see why you think it would last longer than ketamine.
DXM is also a Sigma 1 agonist at 205 nM (more than NET)

What makes you think Sigma has something to do with neurotoxicity?
 
30mg is the therapeutic dose (for coughs) of course there are effects.
I don't know what makes you think DXM is long lasting as wiki states a half-life of 3-5 hours, though the effects on the brain last longer than the DXM does I can't see why you think it would last longer than ketamine.
DXM is also a Sigma 1 agonist at 205 nM (more than NET)

What makes you think Sigma has something to do with neurotoxicity?

http://www.bluelight.org/vb/threads...amine-neurotoxic-What-does-it-do-to-you/page3
 
hello guys
in a few days i'm going to do use some meth to have some fun but just for 1 day (so no meth binge or sleep deprivation) i will use it only 2 times (maybe 3) but only during weekend but since i'm concerned about neurotoxicity i decided to buy a bunch of supplements to try to reduce it
so far here is the supplements i will take 3 days before, just prior and after using it
Melatonin 40 mg extended release
selenium 500 mcg
magnesium maleate 1gr (maybe more)
Alpha lipoic acid 3gr
Alcar 10 gr
Coenzyme Q10 1gr
multivitamin
zinc 100mg
Ibuprofen (only prior to use) 1gr
Aspirin (only prior to use) 1gr

so does this combo sound good ?
if there are better antioxidant or neuroprotectant please tell me
thxx!

i very very rarely use drugs
in the past i have used alot of GHB but it has been 3 years since i didn't use anything
i should add that i use Agomelatine which is an MT1/MT2 agonist and 5TH2C antagonist which was shown to have strong neuroprotective quality and even protect again glutamate excitotoxicity
 
Last edited:
i have read the Amphetamine-Neurotoxicity-and-Tolerance-Reduction-Prevention threads and every time someone mention a good antioxidant/neuroprotectant someone else pop a study about how this compound or this compound is not a good idea because it can turn pro oxidant/ increase neurotoxicity ??
Melatonin was said to be a strong anti oxidant that prevent meth(amphetamine) neurotoxicity than someone said it would increase neurotoxicity, same for vitamine C ALCAR magnesium the list goes on....
so what to take ? i'm confused :?
keep in mind that i don't take amphetamine often just from time to time at moderate dose but i would like to take some sort of supplements to decrease neurotoxicity
is there supplements that really reduce neurotoxicity that was PROVEN to not work againt you (antioxidant that turn into pro oxidant for exemple)??
thxx!

A succinct, understandable, and complete response is here - 3rd post from the top.
 
I don't think that the instructions are sufficiently cautious. I still think that use of anti-oxidant supplementation and various strategies for tolerance prevention (perhaps including nmda antagonists) would still prove useful. One should also strive to preserve neurological function in the medium term, not just prevent of neurotoxicity-proper.

ebola
 
Found some interesting reading on EA's curcumin and proteasome hypothesis. While I get curcumin does inhibit some very relevant pathways and I can see the logic in the "tolerance break" dosing, acutely it actually gets more complicated.
It appears curcumin inhibits the proteasome at higher doses which is also partly responsible for the neurotoxic effects of amphetamine (looks to be mediated by ROS). Granted curcumin has a lot of pro-survival stuff going for it too.

http://m.jbc.org/content/279/12/11680.short

Also, it turns out me and EA are in the same med class, small world haha. Having beers with him sometime next weekend if you've got anything you want me to ask him about this thread.

What he's told me so far is that curcumin is far too dirty to get clean results from with regards to amphetamine tolerance. He mentioned that he only really thought lipid soluble antioxidants and proper lifestyle will make major differences in most users, but there are a lot of other approaches that seem interesting.
 
MXE/3-MeO-PcP and Kratom

Has anyone els experimented with arylcyclohexylamines like Methoxetamine or 3-MeO-PcP in this area?

I've found small (up to 20mg) of methoxetamine "helpful" if taken end the end of the day when using amphetamine. Definitely takes the edge off for me. 3-MeO-PCP is not something I would take the same day as amphetamine as I find it very "manic" on it's own, but the next day it appears to have some restorative properties in low doses (~3-6mg, no tolerance).

There obviously aren't any studies on these, but the mechanism should be similar to DXM/magnesium, but potentially stronger.
-------------

Another thing I have taken many times the same day as (low dose) amphetamine is kratom. Generally a stimulating strain like Maeng Da or Green Malaysian and usually starting 3-4hr after the last (and generally only) dose of amphetamine. I'm somewhat hesitant mixing things with stimulant properties together, but the results have been quite good.

Normally around 3-4hr after taking 20-40mg amphetamine (not pharmaceutical grade, so keep that in mind) is when I start to feel a bit of a crash setting in, lethargy and some mildly unpleasant physical symptoms. Taking 2-4 grams of kratom seems to bring the effect of the amphetamine back to near where it started and remove the physical discomfort. From that point forward I usually don't take any more amphetamine as I no longer feel it's necessary, but the effects can last a very long time (8-12 hrs vs 3-6) when taking a small (for me) dose of kratom every few hours. There definitely seems to be synergy between the two with highly complimentary effects. As kratom has a wide alkaloid profile I think it would be hard to pinpoint all the mechanisms, but from what I understand some of the alkaloids in kratom have NMDA antagonist effects (which are believed to help mediate kratom tolerance/dependency and also help when using kratom for opiate withdrawal).

Kratom also appears to be high in catechins (similar to green tea), and I was told be a reputable user here that after GCMS analysis it also seems to have a high vitamin E content (which could help prevent the primary alkaloids from degrading over time in the powdered leaf).


So between the NMDA antagonist effects, the antioxidants (vitamin E / Catechins etc.), alkaloids with muscle relaxant (Speciogynine, Paynantheine), anti-hypertensive/vasodilator (Mitraphylline, Rhynchophylline), analgesic, and stimulant alkaloids (that likely work via a different mechanism than amphetamine itself), kratom has a lot of potential ways to be beneficial for amphetamine users.

Maybe those who are better in the pharmacology area could elaborate/speculate?



**Btw, this information should be taken with a grain of salt and caution should be exercised should anyone wish to try the combination. Kratom shares some alkaloids with yohimbe which is not something I think should be mixed with amphetamines, and I know there has been at least one report of a seizure mixing kratom with modafinil, so keep that in mind. While my experiences have been wholly positive, I'm not using large recreational doses of either substance and what works well for me in low doses could be dangerous for someone else with a higher dose of either substance, taking them at the same time, or when taking kratom prior to amphetamine etc.

Also, I think if someone is just looking to use kratom for the come down phase (rather than for stimulant synergy), most of the negatives could probably be avoided by sticking to red vein strains (Borneo/Bali) which are much lower in the stimulating alkaloids.

YMMV.
 
Last edited:
I don't think that the instructions are sufficiently cautious. I still think that use of anti-oxidant supplementation and various strategies for tolerance prevention (perhaps including nmda antagonists) would still prove useful. One should also strive to preserve neurological function in the medium term, not just prevent of neurotoxicity-proper.

ebola
Didn't notice this reply earlier.

NMDA antagonists aren't really that necessary to control tolerance- tolerance can be completely controlled, or even reduced, by doing daily, moderate to high intensity aerobic exercise. Increasing #hours exercising/week will lower tolerance on its own.
Besides, if you do endurance exercise while on it, like distance running, you'll often experience euphorias, sometimes very intense euphoria. ;)

I've used amphetamines for slightly over 14 years now, and I've never routinely used NMDA antagonists like DXM outside of infrequent use of sleep aids containing it. Even so, I do suggest using supplemental magnesium when bruxism or muscle cramps routinely occur as side effects though. A high enough dose (100% DV in a bioavailable form can alleviate those effects fairly rapidly; even higher depending on the severity) assuming amphetamine is the cause. Also happens to reduce tolerance.
 
Last edited:
In regards to above post, I find Magnesium Glycinate ~1500mg to work wonders for helping to reduce muscle tension while on stimulants.
 
Lactulose may reduce methamphetamine neurotoxicity by reducing ammonia levels

I've been trying to find as many ways to limit meth neurotoxicity before my next party... I came across this & wanted to share this possibly useful method for reducing neurotoxicity. This study suggests that the laxative lactulose might reduce neurotoxicity of meth (and likely other amphetamines) by reducing ammonia levels.

sum-up http://www.neurorexia.com/2012/10/20/methamphetamine-packs-a-one-two-punch/

The full text of the actual research paper is http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464918/

Two US researchers were investigating whether ammonia buildup in the body and the brain during meth 'binge' use contributes to neurotoxicity effects They theorized that ammonia buildup may be a factor in neurotoxicity because meth may also reduce liver processing and excretion of toxins, thereby raising ammonia levels (see the paper for a thorough explanation). the researchers set out to test if this buildup of ammonia in the brain contributed to to meth-induced neurotoxicity. They first showed that a meth-binge of 4 injections in a day was enough to induce liver toxicity, and that this correlated with an increase in ammonia measured from both blood and the brain. They then showed that lactulose, a drug that can help the excretion of ammonia out of the body, can inhibit the increase in ammonia, but not the amount of meth that eventually ends up in the brain..

They found that surprisingly, neither meth nor ammonia alone produced significant dopamine and serotonin neuron loss; however, when both were infused into the brain together, the rats lost a significant amount of these nerve terminals. They also showed that when rats were pre-treated with the laxative lactulose, the rats had lower ammonia levels, lower glutamate levels (a key cause of neuron exotoxicity), and also experience reduced neurotoxicity. In particular, i was quite excited about the result that there was reduced damage to serotonin and dopamine neurons, because i worry most about the permanent damage using amphetamines may cause, more so than the dopamine depletion (which can eventually be recovered.)

What the research suggests is that if we can inhibit the liver damage caused by meth, we can reduce ammonia levels and at least partially reduce some of the damage to the brain. This is important as the liver is much more readily accessible to drug treatments than is the brain. While the precise mechanisms behind meth-induced liver damage is not yet known, the researchers think that pathways involved in hyperthermia-induced liver damage may be involved.

Lactulose reduces overall ammonia levels via increasing excretion of ammonia from the body. Its laxative properties make food leave the intestines faster, especially protein, which breaks down to produce ammonia. (this is discussed thoroughly in the paper). For this study, rats received lactulose (5.3 g per kg of body mass) every 12 hours for 2 days before meth treatment.

In the paper, 'binge' meth use meant 4 administrations of 20mg/kg of meth to the rats every two hours over one day. Keep in mind this is a shitload of meth! For me it would mean .5 every 2 hours in one day! In real life, I would usually use only .1 over 2 days.
By my calculations, to repeat the lactulose treatment on myself following this methodology, I would need to take 275g of lactulose per dose if i wanted to try myself. My local chemist stocks 'Actilax" which is pure lactulose in solution. The recommended dose for adults is 15-30ml of 3.3g/ml (so thats 45-60gs per recommended dose). I think i may try it this weekend and see how things go, but i will stick with the recommended dose, seeing is i use a fraction of the amount of meth used in this study. i dont think it'll harm my experience because the research suggests that lactulose decreases overall ammonia in your body, but did not affect the amount of amphetamine reaching the brain. the only impact i can see is if it changes urinary pH and therefore excretion rate....

other notes:
I was only able to find a little information about ammonia and its relation to amphetamine neurotoxicity on bluelight here, and it was quite limited. I think it is also important to share the mechagism by which ammonia levels may be increasing neurotoxicity. (http://www.bluelight.org/vb/threads...eurotoxicity?p=5969235&viewfull=1#post5969235).

I also found the PHD thesis of one of the researchers, which may contain additional useful info as it is on this topic. i have not read it yet though. https://etd.ohiolink.edu/rws_etd/document/get/mco1370868834/inline
 
Last edited:
My local chemist stocks 'Actilax" which is pure lactulose in solution. The recommended dose for adults is 15-30ml of 3.3g/ml (so thats 45-60gs per recommended dose). I think i may try it this weekend and see how things go, at worst i dont think it'll harm my experience because the research suggests that lactulose decreases overall ammonia in your body, but did not affect the amount of amphetamine reaching the brain. the only impact i can see is if it changes urinary pH and therefore excretion rate....

Consuming that much lactulose sounds like a good way to have massive amounts of gas and diarrhea.

Also: what works for rats may not readily transfer to humans. Especially in the brain care department. Somehow I doubt that ammonia is exclusively responsible for causing axonal loss in meth users; I think there's a variety of factors working together.
 
Yeah i certainly won't have as much as the study. I actually dont normally take laxatives, so yeah it might be a bit intense to take it every 12 hours leading up to the party. I may try it still at a lowish normal adult dose if i do not get negative impacts (i would stop if i got uncomfortable gas or diarrhea. i hadnt thought much about the practical impacts of trying this haha). There definitly is no way to know it'll work the same way for humans (hmm is that why i haven't found anything about having lactulose and meth with goggle?).

i already take a number of supplements with amphetamines to reduce tolerance and neurotoxicity. Now I am also a regular GHB user on weekends (1,4b) so i already take milk thistle extract, as a liver protectant since 1,4B processes through your liver like alcohol. These may already help my liver health, and thus detoxification and ammonia levels, though no way to know.

to share: my current supplement stack when i take amphetamines.

-piracetam + choline
- magnesium citrate (tolerance, reduce muscle tightness)
-l-theanine (tolerance, reduce anxiety/edginess, antioxidant)
-fish oil
-b vitamins (mitochnodrial support. i also want to add in coq10)
-panax ginseng (helps mitochondria, reduces oxidative stress and reduces neurotoxicity)
-ginkgo (take whenever i use G+amphs because it protects against ecotoxicity from high glutamate levels, which both these drugs impact http://www.ncbi.nlm.nih.gov/pubmed/13130395)
-milk thistle extract with tumeric (from iherb) (liver protection/detoxification).
-vitamin c
I also regularly consume superfood smoothies when i have a big weekend. i make them in bulk and take along to ensure i get good nutrition in a easy to consume form when staying up. My smoothies generally contain oats, fresh fruit fruit, goji berries, leafy veggies, flax seeds, psylium, kefir, sesame oil, coconut oil, coconut solids, almonds or cashews, taurine, sometimes a bit of l tyrosine, and probiotics.

afterwards
-sleep
-b vitamins
-magnesium
-l tyrosine
-5-htp
-rhodiola rosea

I have been using magnesium and l-theanine religiously every time i take amphetamines for the past year (for tollerance effects)....so far i think it has worked amazingly for me. i have always had a very low amphetamine tolerance compared to my friends, and it has barely changed since i started using amphetamines regularly for uni and more frequently when partying. I highly reccomend this strategy for avoiding tolerance build.

I use amphetamines once very few weeks (amphetamine or dexies, rarely staying up more than 24 hrs)....i use meth less frequently..perhaps 5 or 6 times a year. Meth seems to take a much bigger impact on my mental health than speed, giving me crazy mood swings and depression for at least a week after a bit weekend. This is why i want to do everything i can to reduce the impact it has on my brain and body when i do choose to use it. Its been very interesting reading through the different threads and information people have found re reducing neurotoxicity.


I also generally smoke methamphetamine when i use it, but after doing a bunch of research want to try orally this time....it sounds less neurotoxic, less moreish, and possibly more enjoyable. I have recently purchased an e-cigarette which is a lot of fun to smoke, and i think using this at a party may help me avoid the desire to smoke a pipe (an action i really enjoy), because i get a lot of enjoyment out of playing with the vapor from the e cigarette.
 
Last edited:
Hey, i'm back with my experiences from trying my supplement stack as well as the lactulose thing i posted.

I had 2 1/2 days of partying this past weekend. I stayed up for 40 hrs, went through a little less than a point of meth over the two days.....ended up smoking it all cos all my mates were too. I did have a lot of fun though. the second night i got about 5 hours sleep. Plan was to behave after that but were still people partying at my boyfriends house and i ended up smoking alittle more over the day though not heavily. Then called it a day at 4pm, took it easy, got a full 8 hours sleep the next night.

I was pretty religiously with my supplements, especially magnesium, l theanine, selenium, and ibuprofen. I was dosing ibuprofen at the max dose every 5 hours or so. Ate at least 4 small meals a day and drank lots of water (eating on amphetamines isn't a problem for me..i get hungry regularly and cant imagine not eating). also took b vitamins, milk thistle, vitamin c, gingseng, and fish oil throughout. I have an e ciggarette and was smoking nicotine (~6mg/ml) throughout the party too.


I did try the lactulose thing: started taking a 15ml dose (lower end of adult dose) 36 hrs before the party. i had two more 15ml doses before the party, 12 hr intervals like the paper did. then i took two more smaller (12ml) doses during the weekend (ran out..should have brought the whole bottle with me). It encouraged my digestive system to move a little faster before the weekend, though i was never uncomfortable and did not get diarrhea. once the weekend started i didnt have any bowel movments till near the end despite the laxatives.

next time, i think i will try 20 ml doses 4x over 48 hrs before party time. Possibly continue to take it every 12 hrs at the party though if i'm not getting bowel movements when taking stuff it may be pointless (and could increase dehydration because it draws water into your intenstines? hmm)


Did it make any difference to how i felt/feel now?
i felt pretty clear headed throughout...never felt very 'fried' like i sometimes do after partying for that long. But that is just a judgement call ad the fact i havent partied in ages probably affects this too.

My boyfriend who was taking most of the supplements but wasn't trying lactulose got quite a bit of hallucinations towards the end..while i didnt get any visual hallucinations, even after being up for ages.

i felt a bit sketchy, exhausted, and somewhat emotional for two days after....managed to do some things i needed to get done without too much struggle. Today i'm feeling pretty good. I'm not getting strong emotional responses to music etc yet which to me is a sign my neurotransmitters havent returned to normal, but i dont feel depressed. i feel pretty clear headed and not scattered. So far it certainly hasn't negatively impacted my brain and it may have helped, i'm glad i feel fairly functional right now. i will need to see how i feel toward the end of the week, if i get any more mood swings or depression.

I would try this regime again next time i have a big weekend.
 
Does the timing of taking these supplements matter? I am thinking of a stack like this

1g Vit C
1500ui Vit E
300mg Selenium
200mg ALA
1500mg Acetyl Carnitine

Should I take this during, after, or before the meth goes in? Or repeatedly?
 
I dont know about the Vit E and the Selenium but the others seem like a good Idea for a Pre (so before) load!
 
Does the timing of taking these supplements matter? I am thinking of a stack like this

1g Vit C
1500ui Vit E
300mg Selenium
200mg ALA
1500mg Acetyl Carnitine

Should I take this during, after, or before the meth goes in? Or repeatedly?

Selenium and other minerals also have prooxidative effects, take only on off days. Zinc and magnesium are the minerals I would take while on.

What do you guys think about Glisodin and C60 olive oil? From what I have gathered they seem to be two of the most effective radical scavengers todate.
 
I have to ask...I read threw all of this and it's obviously informative but I still am unsure of how to get the most out of my adderall 20mg XR ...

let's say tolerance isn't the issue etc etc ..

besides sodium bi. And empty stomach , alkaline diet? ...anything else and only hydrate with water avoiding acidic acid/critic/etc ?
 
Top