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Fasoracetam and gaba receptor recovery

cdin

cdin

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Ok, so from what i understand literature wise https://www.wikigenes.org/e/chem/e/198695.html that fasoracetam can cause upregulation of gaba-b receptors.
having been on somewhat of a multi-year booze, benzo, g, phenibut and gabapentin gabagoround I was starting to get a little.... jumpy. Anyhow, after an
extended period of time I got sick of it, ordered several grams of fasoracetam and in my personal experience found it wonderful for both helping a taper
along and "restoring the magic" of PB, which i intend to keep by using it very sparingly. It also seems to mitigate somewhat the immediate withdrawal response
of both PB and G. This is pretty great in my book, and additionally gets me thinking: are we on the verge of a slew of compounds that upregulate receptor systems????
what a boon it would be to have selective upregulation of specific systems! Thoughts, additional information anyone?
 
I'm glad this drug has been beneficial for you, but a priori, receptor upregulation is no more of a boon than downregulation, which, in the presence of the right stimulus, homeostasis has taken care of since the days of yore. I suspect most drugs upregulate something in the course of their actions, just not the target receptor (in the case of agonists), or often with unpleasant effects (in the case of desired upregulation of an antagonised target).

In the case of fasoracetam, it isn't particularly surprising that increased excitatory activity (AMPA receptor-mediated) results in a compensatory boost in inhibition, and substrates for all those things you like. :)
 
The mechanism of action of valproic acid is unknown. Effects of the drug may be related, at least in part, to increased brain concentrations of the inhibitory neurotransmitter GABA. Animal studies have shown that valproic acid inhibits GABA transferase and succinic aldehyde dehydrogenase, enzymes which are important for GABA catabolism. Results of one studY indicate the drug inhibits neuronal activity by increasing potassium conductance. In animals, valproic acid protects against seizure induced by electrical stimulation, as well as those induced by pentylenetetrazol (McEvoy, 1991).

Sadly it's toxic to the liver aswell.
 
well, it's only a boon if you've fucked yourself up the opposite direction obviously, though in the case of somone like myself that suffers from anxiety problems the general gaba-b upregulation is kindof something i've been looking for. So more specifically now, are there known agents that upregulate other systems? I just did some casual googling and didn't come up with much
 
NMDA antagonists can result in the upregulation of NMDA receptors (if dosed chronically: http://www.jneurosci.org/content/16/7/2172.full.pdf) and serotonin 1A receptors (after a single dose: http://www.sciencedirect.com/science/article/pii/S0006899397001595).

On the GABA receptor upregulation front, there is indirect evidence for the effectiveness of Bacopa monnieri (reduced epilepsy was used as a proxy; http://www.jbiomedsci.com/content/19/1/25), which might be worth a try, and bicuculine (http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.1988.tb04848.x/abstract) which you probably don't want to try. There are GABA receptor antagonists out there that might be expected to produce the same effect, but don't. Flumazenil, for example, prevents upregulation of alpha-4 subunits of the GABA-A receptor (http://www.ncbi.nlm.nih.gov/pubmed/17403139). It's probably not much fun while you're on it, though.
 
Jonneh said:
NMDA antagonists can result in the upregulation of NMDA receptors (if dosed chronically: http://www.jneurosci.org/content/16/7/2172.full.pdf) and serotonin 1A receptors (after a single dose: http://www.sciencedirect.com/science/article/pii/S0006899397001595).

On the GABA receptor upregulation front, there is indirect evidence for the effectiveness of Bacopa monnieri (reduced epilepsy was used as a proxy; http://www.jbiomedsci.com/content/19/1/25), which might be worth a try, and bicuculine (http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.1988.tb04848.x/abstract) which you probably don't want to try. There are GABA receptor antagonists out there that might be expected to produce the same effect, but don't. Flumazenil, for example, prevents upregulation of alpha-4 subunits of the GABA-A receptor (http://www.ncbi.nlm.nih.gov/pubmed/17403139). It's probably not much fun while you're on it, though.
Click to expand...

Bacon does NOT upregulate gaba at all, it normalizes gaba in epilepsy, that bullshit spreads everywhere like crazy after one guy posted this on imminst.

Kava Kava can reverse phenibut toleramce, magnolia bark has an anecdote of extreme potentiation however that can be in a PA way so not a long term tolerance solution but I haven't done work behind any of these like my past memantine project.

cdin said:
Ok, so from what i understand literature wise https://www.wikigenes.org/e/chem/e/198695.html that fasoracetam can cause upregulation of gaba-b receptors.
having been on somewhat of a multi-year booze, benzo, g, phenibut and gabapentin gabagoround I was starting to get a little.... jumpy. Anyhow, after an
extended period of time I got sick of it, ordered several grams of fasoracetam and in my personal experience found it wonderful for both helping a taper
along and "restoring the magic" of PB, which i intend to keep by using it very sparingly. It also seems to mitigate somewhat the immediate withdrawal response
of both PB and G. This is pretty great in my book, and additionally gets me thinking: are we on the verge of a slew of compounds that upregulate receptor systems????
what a boon it would be to have selective upregulation of specific systems! Thoughts, additional information anyone?
Click to expand...
Memantine pretty much was the solution for everything except gaba agonists this one would fill the gap.

Either way I know of a ton of chemicals that completely end tolerance and withdrawal issues more interesting then mem but didn't have any time to start a project on them like I did with mem

MeDieViL said:
Memantine pretty much was the solution for everything except gaba agonists this one would fill the gap.

Either way I know of a ton of chemicals that completely end tolerance and withdrawal issues more interesting then mem but didn't have any time to start a project on them like I did with mem
Click to expand...

lol bacon, I meant bacopa, I turned a broken tablet into a full computer by connect a tv, USB keyboard and mouse to it, need to turn off this autocorrect this, and also copying text is annoying if you use a tablet as a computer.
 
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I suppose racetams may actually make benzodiazepine withdrawal worse by increasing glutamatergic neurotransmission. Benzodiazepine withdrawal is mostly due to the glutamate system being over-active, i.e. when you increase GABA action through benzodiazepines, then your body produces more glutamate trying to maintain homeostasis. When you stop taking benzodiazepines, your body is still producing a lot of glutamate, way more than needed and your GABA receptors are downregulated as a result of benzodiazepine use. What you want is indeed GABA receptors upregulation and it makes sense that a racetam would cause it indirectly, but first it will make your withdrawal worse.

I actually used piracetam at a dose of 1,200mg a day for a few weeks, I guess, but I realised that it was making me more depressed and irritated. Earlier I had also taken DXM for benzodiazepine withdrawal, which worked well as long as I was taking it, but then I suffered from some rebound effect and piracetam could augment it.
 
adder said:
I suppose racetams may actually make benzodiazepine withdrawal worse by increasing glutamatergic neurotransmission. Benzodiazepine withdrawal is mostly due to the glutamate system being over-active, i.e. when you increase GABA action through benzodiazepines, then your body produces more glutamate trying to maintain homeostasis. When you stop taking benzodiazepines, your body is still producing a lot of glutamate, way more than needed and your GABA receptors are downregulated as a result of benzodiazepine use. What you want is indeed GABA receptors upregulation and it makes sense that a racetam would cause it indirectly, but first it will make your withdrawal worse.

I actually used piracetam at a dose of 1,200mg a day for a few weeks, I guess, but I realised that it was making me more depressed and irritated. Earlier I had also taken DXM for benzodiazepine withdrawal, which worked well as long as I was taking it, but then I suffered from some rebound effect and piracetam could augment it.
Click to expand...


I think it'd be better in that case to take a GABA antagonist, if you are willing to get worse before better, a GABA antagonist is going to do pretty well, Thujone is prolly a good option. Wouldn't recommend caffeine, as that can antagonize GABA at the cost of adenosine. Then again one can try raising their levels of other inhibitory transmitter receptors (adenosine for example). DXM I would imagine might cause things to get worse... NMDA antagonism -> NMDA upregulation -> bad. Thujone will cause upregulation of GABA, while relaxing you through 5-ht3 antagonism. You may rebound a bit with some nausea and slight anxiety, but it will surely be negated by the relief offered by the thujone.
 
MeDieViL said:
Bacon does NOT upregulate gaba at all, it normalizes gaba in epilepsy, that bullshit spreads everywhere like crazy after one guy posted this on imminst.
Click to expand...

Well, 'normalise' is synonymous with 'upregulate' under those conditions, which is why I called it indirect evidence. Perhaps 'circumstantial' would have been more accurate.
 
Jonneh said:
Well, 'normalise' is synonymous with 'upregulate' under those conditions, which is why I called it indirect evidence. Perhaps 'circumstantial' would have been more accurate.
Click to expand...
in epilepsy this has no relevance to well anything...
 
DO NOT take ghb in conjunction with fasoracetam.

I repeat do not..

When taking fasoracetam ghb effects are totally blunted and with knowing how GHB behaves and the dose response curve of possible neurotoxicity it is safe to conclude this is a dangerous combination if it can strongly abate the cognitive dysfunction (sedative /amnesia action) of lower, / higher dose ghb(also benzos/alcohol). Due to ghbs proposed neurotoxicity on extrapyramidal neurons (clinically demonstrated in grip control tasks) mediated by glutamatergic transmission it is best you all avoid this combo. (based on current knowledge)

Also many believe dxm memantine etc dramatically improve their brains...and or prevent tolerance... Antagonism leads to increased Receptor synthesis in order to normalize the antagonism. If you stop them then there are excess receptors that were actively being used but now many are phosphorylation and worthless as they can bind the drug ligand but they cannot complete the signal cascade because the phosphorylation enzyme or Receptor drug complex cannot transfer the phosphoryl group easy and also because the transferee is down regulated as a result of high demand for this. Effectively leading to inability to recycle these through endocytotic means..

Google endocytosis Receptor phosphorylation mu opiate receptors and look at any of the examples your mind may be blown if you let it happen.
Zedsdead
 
Is it bad in that it could promote people to use more despite neurotoxic effects, or bad in another way?
 
Hi, even though it told me to read a bunch of stuff before I could post, and I read those items, I still can not post in "other drugs" about fasoracetam questions. This thread is the closest to what I want to know so let me please ask my questions here.
First off, even the vendors do not provide any information about whether this is a water soluble racetam that works best on an empty stomach, or a fat soluble, racetam, which works best with food.
Another question is this-- I've spent the last month kicking a nasty phenibut addiction, and the fact that this acts differently on the gabba b receptors and is not expected to cause addiction is a light of hope, that I can get something close to that experience. From what I have read it allows more of the gabba that is in your brain to make it into those gabba b receptors, and from my first tests, it certainly produced some familiar sensations, although not as strongly as I had hoped. My question is if I used picamilon, which provides a novel, but barely noticable gabba enhancing effect, to stack with fasoracetam, would this feel more like that wonderful buzz I used to enjoy on phenibut?
Secondly, I'd like to know if fasoracetam would be useful in fighting Phenibut withdrawals. Much of what I have found online sounds very encouraging, but I have a life and death reason for asking this. My wife and I both got addicted to phenibut before she got pregnant. I was "pushing the edge" by taking it three times a week instead of two, and she was absolutely stupid and took it daily, raising her dose up to three times before admitting to me that she did this. She knew how addictive it is-- but she was depressed. When I did some research and told her drug withdrawals during pregnancy can result in premature birth or stillbirth she freaked out, so she is remaining on a maintenance dose and trying to taper. I have found sparingly few of the things I used to help my own withdrawals are safe to take during pregnancy. taurine, twinlabs gabba plus, which has niacinamide and inosutol to help GABA cross the BBB (I have also read some theories that GABBA will cross the BBB, if your brain actually needs it badly enough-- in any case, it has a useful enough effect on the GABBA receptors outside of the brain. Of the herbs I use chamomile and skullcap are the safest, and I have found bailcalin, an extract of skullcap, to be very useful. How about fasoracetam? It is a drug for which there is little information, but the body seems to tolerate these drugs well... I am literally weighing the risks of stillbirth, doing nothing, or birth defects using a novel compound about which little is known. DXM is good for withdrawals, if you don't get hooked on that as well, also known to be safe during pregnancy. Also not known about fasoracetam is onset and duration. We also used amanita muscaria during the last pregnancy, and it is a useful gabaergic drug that seems not to harm the baby.
 
Since someone bumped this old thread I figured I'd add this anecdote: I was able to stop phenibut cold turkey after going through 50 grams in a week or so with zero withdrawal. Normally this amount in such a short time would have me inside of a 72-hour sleepless panic attack. The only supplement I was using at the time was 100mg/day of fasoracetam. Take that for what it's worth.. there have been many other anecdotes of others having similar results. It would seem that this nootropic/drug indeed has some interesting effects at GABAB.
 
I'm bumping this as I'm currently trying to withdraw from a two year daily Phenibut and Gabapentin addiction. This all happened due to ignorance and a scary disease I have. Both have been very helpful for nerve pain. But I want to try and get off now to see if the disease process is healing. I've been using Fasoracetam and Aniracetam as a stack as I decrease my Phenibut dose. I've come down from 3400mg per day to as of today 1050. I'm doing a 10% taper per week right now although I went much faster before I got this low. So far I've had no issues and in fact I feel better than I have in quite awhile.

So I'm hoping anyone else that's trying this may have some input here. I need all the encouragement and advice I can get.
 
I was under the impression that fasoracetam up regulates GABA b receptors because it's an antagonist. By the way, it's been disproven thoroughly that Gabapentin is a GABA b agonist. Most people withdraw from it without issue.
 
It is a Gaba b receptor antagonist, it's supposed to be an anxiolytic as well and seems to function as such but I have read of a couple adverse reactions to it actually causing anxiety. An increase in glutamatergic action as well as GABA b antagonism seems like this would be a likely result. I will be trialing this soon, I was hoping to use it as an anxiolytic but we will see how I react to it. It seems to provide favorable results for most.

Aniracetam and Coluracetam seem to be much better and more dependable anxiolytics. GABA b antagonism during acute withdrawal from GABAergics seems like it would make things worse. If I were in that situation I would just do a slow taper to whichever GABAergic I was using and then try the fasoracetam during the post acute withdrawal phase. The guy that posted this on longecity didn't seem to experience a miracle cure and just ended up using it with Phenibut. It's really difficult getting past the acute withdrawal phase especially if GABAergic drugs are what they were using to self medicate their pre existing anxiety with. It's a crapshoot. GABAergic drugs are great at releiving anxiety but once you are dependant it becomes nearly impossible to get off of them as the anxiety problems are many times worse than when they started off. It is a special kind of hell.
 
How can a GABA antagonist be anxiolytic? It causing anxiety would be quite obvious, but it's very interesting that seemingly only a fraction gets anxiety from fasoracetam - when it is able to up-regulate GABA-B, it must be quite potent and actually I haven't read a single report of it causing intense anxiety. Well, haven't read much reports overall though, but if it was like a GABA-A antagonist, I think nobody would take it repeatedly because it would cause horrible anxiety and we'd know that ... either there's something special about GABA-B, or it acts indirectly - both options make it quite intriguing.
 
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