Preventing Amphetamine tolerance

[AlexxRed]

What do people think of the following method of preventing Amphetamine tolerance?



Taken from this study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695574/

 

[4meSM]

So correct me if I'm wrong. The OP is basically saying that if you reduce your dose for a week then you'll feel stronger effects once you take the full amount again?
Well yeah, this is how tolerance works.
If you have a habit of taking 8 shots of espresso every morning and then suddenly cut back to 1 shot of course you're going to feel more stimulated once you go back to slamming your usual 8 shots at once.

The real issue is how long will it take for your tolerance to go back to its previous levels? In most chronic users tolerance will increase pretty quickly, this has to do with tachyphylaxis.

Morover, by drastically reducing your dose you will essentially put yourself in withdrawal, so you might as well take a real break instead (if possible) which will be much more effective, at least when it comes to stimulants such as amphetamines.
Although if you can manage on a much lower amount of amphetamines by all means go for it, in fact one should try to stay on the lowest dose possible (specially for long-term use).

 

[AlexxRed]

So correct me if I'm wrong. The OP is basically saying that if you reduce your dose for a week then you'll feel stronger effects once you take the full amount again?
Well yeah, this is how tolerance works.
If you have a habit of taking 8 shots of espresso every morning and then suddenly cut back to 1 shot of course you're going to feel more stimulated once you go back to slamming your usual 8 shots at once.

The real issue is how long will it take for your tolerance to go back to its previous levels? In most chronic users tolerance will increase pretty quickly, this has to do with tachyphylaxis.

Morover, by drastically reducing your dose you will essentially put yourself in withdrawal, so you might as well take a real break instead (if possible) which will be much more effective, at least when it comes to stimulants such as amphetamines.
Although if you can manage on a much lower amount of amphetamines by all means go for it, in fact one should try to stay on the lowest dose possible (specially for long-term use).

What do you think of supplements like l-tyrosine to assist with reducing tolerance?

 

[4meSM]

What do you think of supplements like l-tyrosine to assist with reducing tolerance?

I would have to look into it but I really doubt it.
Amphetamine tolerance and desensitization is more complex than your brain not having enough dopamine.

The problem is not really dopamine itsef, it has more to do with changes within the receptors. Some receptors will decrease the rate at which they release dopamine into the synapse, while others will decrease in numbers (downregulation), this all happens through multiple mechanisms which aren't even that well understood as far as I know.

I have seen some stuff about NMDA antagonists being able to prevent or even reverse (to a degree) amphetamine tolerance. I personally like to supplement with magnesium if I'm doing amphetamines, I think it's fairly weak as an nmda antagonist but it does have plenty of benefits.
There is some interesting stuff about NAC (N-acetylcysteine) as well, not sure how useful it would be in this case but I think it's worth researching. I mention it because it appears to be pretty safe and it's already used to treat other issues.
It's best to avoid taking random stuff (even "health supplements") as it could do more harm than good, always try to look for reliable sources.


Otherwise, if one can't find a way to prevent tolerance then the best thing to do is to avoid doing things that will for sure make it worse.
For instance, if you wish to continue to use amps therapeutically for a long time then don't take more than you have to, don't use them to get high and definitely don't binge on them for multiple days without sleep.
If you're using them recreationally then I think the only think that actually works is taking regular breaks. But even with breaks, if one gets into the habit of taking very high doses and going on binges sometimes low doses will never work again (at least not like they used to).

 

[thegreenhand]

Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine release in a memantine-like fashion and protect against behavioral sensitization - PubMed

In contrast to what has generally been found using prototypical NMDA receptor antagonists, these data regarding the effect of memantine, nitrous oxide, and xenon support the hypothesis that activation of certain NMDA receptors (possibly those containing the NR1a/NR2D subunit) in the NAcc is...

pubmed.ncbi.nlm.nih.gov

with regards to the NMDA antagonists here is one study claiming that xenon and nitrous oxide can potentially affect the "development of behavioral sensitization to amphetamine"

 

[4meSM]

Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine release in a memantine-like fashion and protect against behavioral sensitization - PubMed

In contrast to what has generally been found using prototypical NMDA receptor antagonists, these data regarding the effect of memantine, nitrous oxide, and xenon support the hypothesis that activation of certain NMDA receptors (possibly those containing the NR1a/NR2D subunit) in the NAcc is...

pubmed.ncbi.nlm.nih.gov

with regards to the NMDA antagonists here is one study claiming that xenon and nitrous oxide can potentially affect the "development of behavioral sensitization to amphetamine"

Yep. The fact that NMDA antagonists can prevent tolerance from developing has been known for 30 years or more, at least when it comes to amphetamines and opioids.
It's just difficult to translate those findings into an actual practical solution.

There are also many testimonies of people using stuff like ketamine, dxm or memantine to keep tolerance at bay.
But for how long?
In many cases you have to take those drugs pretty often so now you end up with 2 different habits, plus many common nmda antagonists hit other receptors as well which might not be ideal.

 

[Gaffy]

How to prevent Haldol induced dopamine receptor desensibilisation and prevent withdrawal issues due to overloaded neurons exchanging too much dopamine without Being able to handle the exchange due to tarification

 

[Gaffy]

How to prevent Haldol induced dopamine receptor desensibilisation and prevent withdrawal issues due to overloaded neurons exchanging too much dopamine without Being able to handle the exchange due to tarification and leasing treatment

Same issues

 

[thegreenhand]

Yep. The fact that NMDA antagonists can prevent tolerance from developing has been known for 30 years or more, at least when it comes to amphetamines and opioids.
It's just difficult to translate those findings into an actual practical solution.

There are also many testimonies of people using stuff like ketamine, dxm or memantine to keep tolerance at bay.
But for how long?
In many cases you have to take those drugs pretty often so now you end up with 2 different habits, plus many common nmda antagonists hit other receptors as well which might not be ideal.

i mean i can definitely say that doing a fat balloon right after nice line of speed is incredible lol

i don't use amphetamine often enough to experiment with this myself though. i agree that this is likely to lead to some sort of poly substance habit rather than reduced tolerance