Microdosing dextroamphetamine to reverse tolerance/increase sensitivity

[someguyontheinternet]

Axon->synapse->receptor/dendrite

The term bouton I think covers the connection between an axon and a dendrite, while axons do have receptors those are referred to as presynaptic receptors and postsynaptic receptors are the ones that we traditionally think about in neurotransmission

Presynaptic receptors are usually involved in regulation of vesicle release because those tend to be ion channels or GPCRs that regulate ion channels that modulate Ca2+ in the presynaptic terminal

 

[someguyontheinternet]

https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/attachment/fac012af-e791-4a5e-9a6f-7ea88bb239a6/gr1_lrg.jpg

Here's a decent image showing the tripartite synapse. There are also astrocytes involved in the regulation of synaptic transmission, they help with ion concentration and transmitter concentration maintenance and uptake. The image shows some receptors and channels that may be on a presynaptic neuron as well

 

[Pissed_and_messed]

it is broken

 

[someguyontheinternet]

Yea I just linked the image instead. It works if you click on the link. Maybe Elsevier has BL blocked lol

 

[Neuroprotection]

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?)

Thanks so much for sharing this. yes, those arguments you found on Reddit are very convincing. i’ve also read more about the subject myself and it seems to be that amphetamine sensitisation, if it does occur in humans, would make them much more susceptible to stress, Depression and addiction.

 

[Neuroprotection]

Also, the field of drug reward, though mainly centred around dopamine, is actually very complex with multiple neurotransmitters involved. Though I don’t really have scientific evidence for this, I feel that amphetamine can be rewarding in different ways depending on who is using it, The amount and duration it is used for and the context in which it is used. all these things maybe subject to a form of sensitisation or tolerance that can affect one’s long-term experience.

 

[G_Chem]

What were the lowest doses you took?? are you suggesting that low doses sensitised you or just that you are particularly sensitive to amphetamine?

Hard to say as o wasn’t keeping super close track, but I definitely feel as if my tolerance has gone down. Used to take 10-20mg minimum, now 5-10 is my usual go-to dosage. I often take as little as 1-3mg for a light pick me up.

-GC

 

[someguyontheinternet]

Hard to say as o wasn’t keeping super close track, but I definitely feel as if my tolerance has gone down. Used to take 10-20mg minimum, now 5-10 is my usual go-to dosage. I often take as little as 1-3mg for a light pick me up.

-GC

Do you use amphetamine on a regular basis?

 

[G_Chem]

Do you use amphetamine on a regular basis?

Hmm depends what you define as regular… I’d say on average 8-10 times a year. Sometimes less if I can’t find any… (It’s not easy for me to find these days, they don’t hand em out like they used to.) But usually around there.

-GC

 

[someguyontheinternet]

We can become more or less sensitive to drugs as we age depending on receptor expression or enzyme/metabolism levels so I think with that sort of sporadic use

 

[G_Chem]

We can become more or less sensitive to drugs as we age depending on receptor expression OE enzyme/metabolism levels so I think with that sort of sporad

Yup and I’m also just one guy. Could be a million factors at play that caused this to happen. Whatever the case I’m not complaining lol. This 30mg cap of brand name has lasted me 5-6 sessions now and still got some left.

-GC

 

[snmfmy]

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 have found that limiting the dose to approx 50 mg oral single admin/day, prevents tolerance even if used multiple consecutive days. It enabled long breaks if wanted and actually causes dose reduction b/c sometimes subjective euphoria is heightened on same or lower dose.

OTOH, use exceeding 100mg/day, or any significant smoking induces tolerance same day when compulsive re-dosing occurred, as well as extreme sympathomimetic and locomotor side effects.

Hope that helps.

 

[snmfmy]

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.

I can unequivocally state that using 50mg orally in a every two or three days intermittent pattern WILL RESULT IN SENSITIZATION in approximately 3 weeks. Once a short break is taken and reintroduce.

Sensitization to the point that the same 50 mg will be almost unbelievably stimulating without sympathomimetic negative effects. And the stimulation, cognitive and sexual with an extreme body high is extended from the normal 24 hours to 36 to 48 hours.

It's almost impossible for this not to occur in my case because I do not like to use daily. I use very small doses when I use and the only way I have been able to reverse the sensitization is a very long abstinence. Or several days in a row of several very small doses throughout the day.

For example, 50 to 60 mg in five or six divided doses throughout the day for a week will abolish the sensitization and institute slight tolerance.

 

[snmfmy]

Yup and I’m also just one guy. Could be a million factors at play that caused this to happen. Whatever the case I’m not complaining lol. This 30mg cap of brand name has lasted me 5-6 sessions now and still got some left.

-GC

I think you might be getting sensitized because of your intermittent and low dose usage.

 

[Neuroprotection]

I can unequivocally state that using 50mg orally in a every two or three days intermittent pattern WILL RESULT IN SENSITIZATION in approximately 3 weeks. Once a short break is taken and reintroduce.

Sensitization to the point that the same 50 mg will be almost unbelievably stimulating without sympathomimetic negative effects. And the stimulation, cognitive and sexual with an extreme body high is extended from the normal 24 hours to 36 to 48 hours.

It's almost impossible for this not to occur in my case because I do not like to use daily. I use very small doses when I use and the only way I have been able to reverse the sensitization is a very long abstinence. Or several days in a row of several very small doses throughout the day.

For example, 50 to 60 mg in five or six divided doses throughout the day for a week will abolish the sensitization and institute slight tolerance.

I would really like to sensitise myself to amphetamine deliberately, after I was traumatised by an episode of anhedonia last year. however, just want to check a few things first.
Does sensitisation affect normal life when not using amphetamine?
for example, are sexual and food reward affected.
What is your opinion on taking tiny doses of amphetamine, e.g. 2 mg per day for about seven days and then taking a few weeks break before taking a proper therapeutic or recreational dose.

 

[snmfmy]

I would really like to sensitise myself to amphetamine deliberately, after I was traumatised by an episode of anhedonia last year. however, just want to check a few things first.
Does sensitisation affect normal life when not using amphetamine?
for example, are sexual and food reward affected.
What is your opinion on taking tiny doses of amphetamine, e.g. 2 mg per day for about seven days and then taking a few weeks break before taking a proper therapeutic or recreational dose.

I think that low of a dose is not going to work.

The heightened erogenous zone sensitivity and libido stays somewhat elevated for days after use and it wasn't like that when I'm not sensitized.

Was not exaggerating about the subjective effects the ones that we like being extended to 36 to 48 hours. It is absolutely unbelievable.

Now I have a very strange physiology. I took somewhere between 500 and 1,000 MDMA tablets, with absolutely no loss of the magic. And I would eat Scooby snacks Thursday, Friday, Saturday and sometimes Sunday. And week after week after week for a couple of years without any negative side effects. So perhaps that is related to the extreme sensitization.

 

[emkee_reinvented]

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.

10 mg Amphetamine is 5 mg dextro-Amphetamine. So I assume you mean 10 mg dextro right. Cause doublin your dextro dose won'make the difference.

That's not a recreative dose but a therapeutic dose. I was on 15-10-10 mg which remained effective, so what the need for micrdosing or raises.

Btw dextro-Amphetamine wasn't that recreative to begin with. It need's l-Amphetamine and dosages 10 x therapeutic doses, talking bout the dextro. DL-Amp probably less then that.

 

[Neuroprotection]

Great answers from everyone so far.
For any of you who have experienced amphetamine sensitisation, would you say it was a good thing?
Are there any bad aspects to it?

 

[klfiend]

Long-lasting effects of escalating doses of d-amphetamine on brain monoamines, amphetamine-induced stereotyped behavior and spontaneous nocturnal locomotion - PubMed

The repeated intermittent administration of relatively low doses of amphetamine (AMPH) produces an enduring hypersensitivity to the motor stimulant effects of AMPH (behavioral sensitization), and this is accompanied by enhanced mesotelencephalic dopamine (DA) utilization/release. In contrast...

pubmed.ncbi.nlm.nih.gov

 

[Neuroprotection]

Long-lasting effects of escalating doses of d-amphetamine on brain monoamines, amphetamine-induced stereotyped behavior and spontaneous nocturnal locomotion - PubMed

The repeated intermittent administration of relatively low doses of amphetamine (AMPH) produces an enduring hypersensitivity to the motor stimulant effects of AMPH (behavioral sensitization), and this is accompanied by enhanced mesotelencephalic dopamine (DA) utilization/release. In contrast...

pubmed.ncbi.nlm.nih.gov

Thank you for posting this. i’ve actually read these studies before, but I just don’t know how this will translate to human behaviour. do you have any ideas?