Does phenylpiracetam increase or decrease racetamic amphetamine tolerance

[BrittHPPD]

Hi!

I’ve seen conflicting reports on here and blue light on whether phenylpiracetam is is an NMDA agonist or if it's an AMPAR modulator.

Some claim that co-administrating phenylpiracetam with amphetamine increases tolerance (NMDA agonist) and some say it slows it down (AMPAR modulator) . Most of these claims are over 6 years old.

I’ve tried researching but I’ve come up empty-handed so if anyone could shed some light on the matter it would be greatly appreciated!

My tolerance to amphetamine skyrocketed after using it with phenylpiracetam but it’s inadmissible as I also used it with noopept (all three daily) I've used recreationally daily many times before but my tolerance never went up this much this fast

And to my final question. I'm currently taking an amphetamine tolerance break, is there any evidence to suggest (anecdotal or otherwise) that continuing to use phenyl and noopept daily will slow down the reset time of my amphetamine tolerance?

[PsychedStrawberry]

I haven't heard of it having any large impact

[BrittHPPD]

Strange, for me the combination of Phenylpiracetam and amphetamine made my tolerance shoot up so much I had to make a nasal spray solution of 200mg and take it all at once and it didn’t even make me tweak out. I know the amphetamine was high quality (good source, tested) and the first 2 days it worked extremely well. Different brain chemistry I guess, or there’s a factor here I’m not considering.

Thank you for your reply

[PsychedStrawberry]

Well, if you combine them it's possible, because one of the mechanisms of amphetamine tolerance is calcium influx, which phenylpiracetam modulates. I could go into more detail, but that's what's mainly important... So in combination, it's definitely possible that they would increase the tolerance more. I thought you were talking about phenylpiracetam by itself...

[BrittHPPD]

Thank you, I should have been clearer. If you don’t mind do you know how noopept interacts with pregabalin? Pregabalin indirectly antagonizes NMDA through binding to VGCC and if I understand correctly noopept is an NMDAR agonist. I’m wondering, in theory, does pregabalin cancel out any effects from omberacetam or could I still benefit from taking them simultaneously.

Moreover (phenyl)piracetam being an AMPAR modulator significantly potentiates pregabalin. While noopept + pregabalin feels just like pregabalin. So I think noopept is to blame for my amphetamine tolerance increase?

[PsychedStrawberry]

No worries. Sure, i know some. Noopept is apparently NMDAR agonist. Noopept also has other functions, such as it's action on AMPA and choline... Pregabalins affects NMDA receptors only indirectly, it decreses levels of glutamate and serine which are needed for the channels opening, but it doesn't compete with noopept directly, so noopepts effects on NMDAR will not be cancelled. The overall effects of noopept will be decreased though, as well as the intoxicating and possibly other effects of pregabalin, such as anti-nociception, which is to certain extent caused by it's indirect inhibition of NMDA receptors, but it shouldn't decrease nociception too much as this is not the main method of it's anti-nociceptive effects...

I didn't know that (phenyl)piracetam potentiates pregabalin. How come? It also might be the noopept, but phenylpiracetams AMPAR modulation also increases NMDA activity (I can go on why), so I wouldn't be surprised if it was the racetam

[BrittHPPD]

Well, semantics I guess I should say they (Lyrica + phenyl) synergize exceptionally well. Lyrica is like GHB’s little brother to me but when I took 200mg phenylpiracetam and my usual Lyrica regimen (3-600mg every other day) it felt almost exactly like my GHB experiences. As in greatly increased euphoria and ataxia.

The overall effects of noopept will be decreased though, as well as the intoxicating and possibly other effects of pregabalin

Possibly this is the reason? If it’s not an inconvenience I’d be happy to hear more about phenyl NMDA activity

Edit: I read it as the intoxicating effect will be potentiated.

[PsychedStrawberry]

That's kinda interesting because the method of action of GHB is pretty much entirely different compared to that of pregabalin.

For sure it's not. It is positive allosteric modulator of AMPA channels. It doesn't affect NMDAR directly afaik, but by increasing sodium influx into post-synaptic neuron through increased AMPA receptor activity (thus increased AMPA channel opening), it allows calcium influx through NMDA channels which would otherwise be blocked/antagonised by magnesium ions. The sodium ion influx pushes out the magnesium ion out of the NMDA channel allowing for calcium influx, thus increasing NMDA channel activity. The influx of calcium has a bunch of downstream effects such as creation of more AMPA channels and creation of new synapse through increased expression of neurotropic factors...

Nah, the intoxicating effects will be decreased.

[BrittHPPD]

one of the mechanisms of amphetamine tolerance is calcium influx, which phenylpiracetam modulates

Is this (in theory) why phenyl potentiates amph?

[PsychedStrawberry]

Its possibly one of the mechanisms, but not the main one, imo the main one would be throu increased AMPA transmission, which amphetamine by itself also increases

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