High dose piracetam therapy to renew NMDA receptors

[kong]

Heavy ketamine user at points. Found piracetam to work well for depression, cognition and resetting my brain in a way. Similar to ketamine in many regards.

Never used either in close proximity to the other.

Can't speak to the reversal of tolerance as the too much time elapsed between piracetam and ketamine binges to know for certain.

 

[Phaxius]

Kind of had a similar thought regarding piracetam and nmda antagonists. While searching for information I stumbled on this old thread along those lines and decided to ressurect it instead of starting a new one.

Is there any evidence that the use of nmda antagonists causes a reduction in nmda receptor density? I have been looking for studies on the mechanisms of tolerance for nmda antagonists for a while now, but seem to only find studies regarding nmda antagonists and the effect on tolerance to opioids and other drugs. Can anyone help elucidate or otherwise point towards information on what causes tolerance to nmda antagonists?

 

[lolwhatzdrugs]

I plugged some noopept with methadone and some 3-meo-pcp the other day. It most certainly did not eliminate the nmda antagonism of the methadone or the low dose 3-meo-pcp. ymmv

 

[Xorkoth]

I have never gotten depressive thoughts on piracetam or any racetam (I've tried piracetam, aniracetam, oxiracetam, and pramiracetam... today I am getting phenylpiracetam too but haven't tried it yet). I do discontinue use for a few months after a month or two on though as I notice it seems to become counterproductive. Also, I find that it often potentiates psychedelics, sometimes greatly. I have never tried it with dissociatives.

 

[lolwhatzdrugs]

I haven't taken enough racetams to commend on depression/suicidality.

 

[SONN]

noopept actually produced the most anxiolytic effect i've ever felt when I combined it with choline(of course), theanine, ginkgo biloba, THC, and .3 grams of psilocybe cubensis

I was giving a class presentation and just wanted to giggle at how much I didn't care what their reactions were.

no depression caused specifically by noopept that I can remember.

 

[dude_87]

According to reply #36 in this thread and this study, "ketamine's primary psychoactive effect is actually caused by the fact that it agonizes AMPA receptors through downstream interactions. In blocking NMDA receptors, it causes the brain to release more NMDA. However, the AMPA receptors remain untouched and therefore get heavily agonized by this excess of unused NMDA. This effect has been found to cause the psychoactive effect as well as the excitotoxicity of ketamine"

Based on this, could extended piracetam supplementation reduce ketamine tolerance?

 

[Cotcha Yankinov]

I would say based on this you wouldn't want to stimulate glutamate receptors, but rather let them up regulate. Long term potentiation might possibly come into play and in that case the long term potentiation boost of stimulating glutamate might outweigh the receptor down regulation, so you would want to use ampakines in that scenario.

The other thing to consider is that ampakines will effect down regulation and up regulation of other types of receptors like dopamine and serotonin that are playing a role in NMDA antagonists intoxication. The specific receptors that glutamatergic activity from an ampakine will down regulate will be the exact receptors responsible for psychedelic action via glutamate, so you might increase tolerance in this way as well, or you could boost LTP and strengthen the connections.