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Microdosing dextroamphetamine to reverse tolerance/increase sensitivity

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Neuroprotection

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Apr 18, 2015
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Apologies if this has been discussed before, but I can’t find anything on it anymore. The idea is that very small doses of dextroamphetamine (2.5 mg) taken by mouth on a daily basis for a few days to a week alters one’s response to a higher dose. apparently, these small doses, whilst barely psychoactive, strongly sensitise the brain. it is then advised to stop the drug for sometime, preferably between one week and one month. once a normal dose of amphetamine(10 mg) is taken, The subjective effects are massively amplified.
I’ve heard many people refuting this on sites like reddit but I can’t help think that there must be something to it if so many people swear by it. I once came across a scientific study that suggested this phenomena was true.
What are your thoughts?
This is important to me because I’m really considering starting psychostimulants to help me get through work.
 
I can't recommend it. It is said that it changes the ratio of different dopamine receptors. I have read reports that people get very uncomfortable state chronically sober after trying it.
 
Pissed_and_messed said:
I can't recommend it. It is said that it changes the ratio of different dopamine receptors. I have read reports that people get very uncomfortable state chronically sober after trying it.
Click to expand...


If possible, can you elaborate on what you mean by uncomfortable? are you talking about people becoming super sensitive to dopamine in the sober state, becoming unusually sensitive to reward/motivation etc? also, I’d be really interested if you had any information on how exactly this could affect dopamine receptor ratio and function.
 
I found A post on Reddit claiming this ultra low-dose amphetamine regimen for reverse tolerance was a hoax but there were so many anecdotes of people claiming to have done this either accidentally or purposely with great effect.
 
someguyontheinternet said:
Honestly that just sounds like waiting for tolerance to go down
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As I said previously, I have no idea if this method works. however, I doubt it’s anything to do with waiting for tolerance to diminish, instead, it’s about inducing chronic sensitisation of dopamine receptors and dopamine signalling. I posted a Study above which suggested sensitisation can occur in humans, with repeated low doses of amphetamine.
 
Whether this method of deliberate sensitisation works in humans is very controversial, this is why I want the experiences of anyone who might have tried it.
 
What is the biochemical mechanism and why is a period without amphetamine necessary if it really is the low doses that are doing it
 
someguyontheinternet said:
What is the biochemical mechanism and why is a period without amphetamine necessary if it really is the low doses that are doing it
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I really have no idea and that’s why I created this thread. nevertheless, sensitising regimens of amphetamine used in animals generally use small doses which may be progressively escalated.
 
If you're trying to find ways around tolerance, you're trying to cheat a system that exists for a good reason in the first place.

Tolerance is our body telling us when enough is enough.

Don't ignore your body.
 
Neuroprotection said:
www.nature.com

Human Response to Repeated Low-Dose d-Amphetamine: Evidence for Behavioral Enhancement and Tolerance - Neuropsychopharmacology

Previously, we reported progressively greater behavioral responses to repeated d-amphetamine in human subjects that represented a potential model of behavioral sensitization. To extend this work, 59 healthy volunteers were randomly assigned to one of three protocols: (1) placebo administered on...
www.nature.com www.nature.com
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That study is not about low doses, they give 0.25mg/kg which means 25mg for a 100kg person. The average human is 70kg
 
I’ve taken low doses a fair amount and do feel more strongly rather low doses of amphetamine compared to most people for what it’s worth.

-GC
 
G_Chem said:
I’ve taken low doses a fair amount and do feel more strongly rather low doses of amphetamine compared to most people for what it’s worth.

-GC
Click to expand...

What were the lowest doses you took?? are you suggesting that low doses sensitised you or just that you are particularly sensitive to amphetamine?
 
someguyontheinternet said:
What is the biochemical mechanism and why is a period without amphetamine necessary if it really is the low doses that are doing it
Click to expand...
there is mechanism and explanation was internally coherent but I don't remember its name and details. I am no sure how proven mechanism is, but it is apparently applied to some other things too.
Neuroprotection said:
If possible, can you elaborate on what you mean by uncomfortable? are you talking about people becoming super sensitive to dopamine in the sober state, becoming unusually sensitive to reward/motivation etc? also, I’d be really interested if you had any information on how exactly this could affect dopamine receptor ratio and function.
Click to expand...
people reported they were tweaking and paranoid sober, then.
 
en.wikipedia.org

Hormesis - Wikipedia

en.wikipedia.org en.wikipedia.org

BTW I wonder if this is not myth ultra-low dose of amphs can cause sensitization of sort, how widely users of street drugs are affected of it. They sometimes get shit that delivers them only ~1 mg of amphetamine or something on one line, then they forget the stuff because it is so shit. But now they have allegedly started hypersensitization.

Well, street drug users have all kinds of clinical and non-clinical weird stuff going on, so, maybe it happens but people don't realize it.
 
Pissed_and_messed said:
en.wikipedia.org

Hormesis - Wikipedia

en.wikipedia.org en.wikipedia.org

BTW I wonder if this is not myth ultra-low dose of amphs can cause sensitization of sort, how widely users of street drugs are affected of it. They sometimes get shit that delivers them only ~1 mg of amphetamine or something on one line, then they forget the stuff because it is so shit. But now they have allegedly started hypersensitization.

Well, street drug users have all kinds of clinical and non-clinical weird stuff going on, so, maybe it happens but people don't realize it.
Click to expand...


Thank you for sharing that. of course, I’ll do a lot more research before I ever try this myself, I was looking to increase reward sensitivity.
 
I read some more about this, and someone on Reddit stated, among other arguments, that if low-dose amphetamine could cause some kind of sensitization, we would be sensitized anyway, because we have endogenous PEA, that is TAAR1- and VMAT-2 agonist, modulating amounts of post-synaptic dopamine, norepinephrine, serotonin and acetylcholine, circulating in our systems all the time, in constantly fluctuating levels. PEA is core phenethylamine, proto-amphetamine.

I can not argument against that. It should mean that sensitization effect is rather modest and limited, or non-existent.

(Ain't post-synaptic correct way to refer what I tried to refer there, BTW?)
 
Pissed_and_messed said:
I read some more about this, and someone on Reddit stated, among other arguments, that if low-dose amphetamine could cause some kind of sensitization, we would be sensitized anyway, because we have endogenous PEA, that is TAAR1- and VMAT-2 agonist, modulating amounts of post-synaptic dopamine, norepinephrine, serotonin and acetylcholine, circulating in our systems all the time, in constantly fluctuating levels. PEA is core phenethylamine, proto-amphetamine.

I can not argument against that. It should mean that sensitization effect is rather modest and limited, or non-existent.

(Ain't post-synaptic correct way to refer what I tried to refer there, BTW?)
Click to expand...
Synaptic rather than postsynaptic because postsynaptic usually refers to the receiving neuron as in the postsynaptic density. The synapse is the area between the neurons but I think you've got the right idea
 
whaaat I've got it all wrong. Wait a minute.

receptor--->axon--->????--->synapse

what is going on here
 
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