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Supplements to up-regulate GABA release.

gaba release upregulate increase #gabaa

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#1 2 Duckets

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Posted 20 August 2020 - 10:24 PM

I'm looking for supplements to increase the release of GABA.

I think my body isn't producing enough GABA due to past Benzo use.

Maybe a good way to increase GABA would be to boost Glutamic Acid Decarboxylase enzyme? Any natural ways to do this?

I cant take anything that binds to the GABA(a) receptors as these make my symptoms worse.

Thanks for your help

Edited by 2 Duckets, 20 August 2020 - 10:27 PM.

#2 ibtisam_midlet

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Posted 21 August 2020 - 10:14 PM

there Phenelzine that will inhibit the enzyme that metabolise GABA to some crappy metabolism, but those drugs are not strong, you would think of some GABA reuptake inhibitor its very strong, theres Tiagabine and Hyperforin( from sant jons wort you need heroic dose)

GRIs can induce a wide range of psychological and physiological effects, including a general and subjective alteration in consciousness, dizziness, blurry vision, diplopia or double vision, nystagmus or involuntary eye movements, amblyopia or "lazy eye", tinnitus or "ear ringing", sedation, drowsiness or somnolence, narcolepsy, tiredness or weakness, fatigue or lethargy, aches and pains, headache, nausea and vomiting, gastrointestinal disturbances, shakiness, disorientation, diminished awareness, impaired attention, focus, and concentration, decreased drive and motivation, stuttering and slurring of speech, confusion, cognitive and memory impairment, mood lift or drop, depression, anxiolysis, disinhibition, stress reduction, euphoria or dysphoria, irritability, aggression, anger or rage, increased appetite and subsequent weight gain, ataxia or impaired coordination and balance, muscle relaxation, trembling or muscle tremors and spasms, paresthesia or "pins and needles", analgesia, respiratory depression, and dyspnea or shortness of breath, among others.

so its not really that best, increasing GABA mean agonizing all the receptors that will made tolerance to its effect less luckly to accure but some GABA receptors made other effect then anixiolytic.

i know what you think but you might like Flubromazolam its very strong GABA A agonist some people die just from 3mg


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#3 Keizo

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Posted 21 August 2020 - 10:44 PM

The best anti-anxiety agent for me has been Selank. (To some extent cerebrolysin but mostly for it's overall effects, and anti-anxiety is one part of that. However I've seen studies on both Selank and Cerebrolysin indicating allosterinc modulation of GABA receptors being potential mechanism of action (at least one possible mechanism for their effects). Both of these drugs are in my opinion not going to cause withdrawals of any kind. Even tho "allosteric modulator of GABA receptors" might bring ones thoughts to benzodiazepines, these two drugs mechanism must be rather different, just thru my experience (and AFAIK no one has had withdrawal taking these).  And interestingly I find them boost stimulants (anything from caffeine to my prescription stims).)

just some cursory searches I did right now: https://www.ncbi.nlm...les/PMC4757669/ https://www.frontier...2017.00089/full


Either way when it comes to most things (except things that act on dopamine) I'm rather reticent to take anything too powerful, because AFAIK the GABA system seems finicky (as does serotonin). If you push it off kilter it might go rather wrong, at least with the more powerful substances (benzodiazepines) whereas taking stimulants in low dosages seems without much any long term consequence. The dopamine system seems much more flexible. So the mechanism by which Selank (and cere) presumably work thru seem a bit subtle, having to do with neurotrophic factors or rather indirect effects on gene expression or general brain function etc (cere had some effect on an enzyme that involves learned fear responses).


I guess you could try some GABA receptor antagonists, like I don't know, fasoracetam maybe. Tho that'd probably be unpleasant and I'm not really sure it's going to have good effects long-term. Cere for sure has (good) long term effects for me personally, selank maybe a bit less so I'm not sure (but selank seems way better for me short term in producing some anti anxiety effect).

#4 Daxter

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Posted 22 August 2020 - 04:01 AM

What are your thoughts on sarcosine?


#5 Keizo

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Posted 22 August 2020 - 12:35 PM

Also I'm pretty sure GABA binds to GABA(a) receptors. So I'm not sure how you'd get around "binds to the GABA(a) receptors" with your idea 2 Duckets  ;)


#6 Keizo

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Posted 22 August 2020 - 02:36 PM

What are your thoughts on sarcosine?


I haven't tried it myself. I've however taken ordinary glycine for long periods (I take about 5-10 grams per day, try to take it most days, it's very cheap if you buy 1kg bags), which I do think is one of the best supplements for me (in the category of dietary/vitamin/mineral supplements) mostly (as far as anything noticeable) just for a mild sustainable calm, improved sleep but also attention. The "weird" thing about glycine is that it can actually cause (for me anyway) some slight stimulation. Just skimming thru some stuff I would guess that sarcosine is vaguely similar to glycine. So the overall effects might be calming or stimulating...... but perhaps sarcosine is more leaning towards the stimulating side. I've read some anecdotes where people experience some stimulation from sarcosine.


The main reason I take glycine is as a health supplement, the idea that if consuming a modern diet with lots of fine meats we might not get enough glycine (collagen, etc) and this might have various somewhat bad effects that the supplementation might reduce. 


I'd also assume that both glycine and sarcosine, since they are chemically very much related, would have more of a short term effect. So for that reason I wouldn't be too worried about trying it, at least not as far as causing any permanent damage with some modest dosages (whatever that is). 


here's just some other random links:



Edited by Keizo, 22 August 2020 - 02:43 PM.

#7 2 Duckets

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Posted 22 August 2020 - 04:40 PM

Thanks for all your replies..


Also I'm pretty sure GABA binds to GABA(a) receptors. So I'm not sure how you'd get around "binds to the GABA(a) receptors" with your idea 2 Duckets  ;)


Right, Gaba does bind to Gaba(A) receptor. Here's the problem. I think from past Benzo use, I get down-regulated GABA release anytime I take anything that is a GABA(A) agonist. Maybe in the mRNA gene expression like GAD65 or GAD67.


Anytime I take anything that PAMs(activates) the Gaba(A) I feel great for a few hours, but then over the next 5 days I get hit with a wave of symptoms. Symptoms include: Anxiety, tremors, insomnia, burning skin, mind racing, Benzo belly, sore muscles, brain fog, lack of reward (lack of dopamine activity in NAc and VTA), anhedonia, ect....


I stopped taking Benzos (diclazepam, etizolam, flubromazepam, ativan, klonopin) over 5 years ago, and I still have withdrawal symptoms anytime after I take anything that tickles the Gaba(A) receptors in a PAM(agonist) fashion. Even taking a 500mg GABA supplement (that is not suppose to cross the BBB) makes me feel great for a few hours but then I get thrown into a horrible wave of symptoms that last 3 to 5 days.


Towards the end of my Benzo use, the Benzos stopped working. No matter how much I took I would be stuck with horrible symptoms.


Things Ive tried post benzo use..






Magnolia Bark





Lithium orotate


and tons more...


All of these things throw me back into a horrible wave of symptoms after they wear off because they all activate GABA(A) receptors..


I even tried GABA(A) receptor Antagonists like..


Ginko Biloba

Incarvillea Sinensis

St. John's Wort


but still I suffer..


So I stay away from GABA(A) agonist, but STRESS also throws me into a bad wave of symptoms that lasts for days! And you cant stay away from stress!


Could it be that Benzo use changed the Gaba(A) subunits and there still not right after 5 years?

Benzos bind to the Alpha 1,2,3,5, and Gamma subunits. Maybe my body stopped making these subunits?


No pharmaceuticals recomendations please. I dont have health insurance.










Edited by 2 Duckets, 22 August 2020 - 04:50 PM.

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#8 Keizo

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Posted 22 August 2020 - 05:25 PM

Yeah I think I know what you mean more or less. For example some months after I completely quit benzos I took Magnolia extract, and that seemed to work very similar to a benzo actually, just way less potent, but effects stopped very quickly. And there did seem to be a slight withdrawal even after just taking it for a few days. Then a bunch of other stuff that was mostly failures.

I think the problem with most herbs and supplements in general (some pharmaceuticals as well) is that they don't have long term effects or they aren't potent enough to notice improvements beyond the days someone takes it.

But with some stuff that is very mild and basically a nutrient I don't see why you shouldn't be able to take it every day, like Magensium or glycine, in some modest dosage.


As far as Selank or Cerebrolysin I'm pretty sure you can't get that on a prescription in the US, or most parts of Europe (someone went to mexico to get cere infusions when they had Alzheimers) but you can buy it from Russia and I'm pretty sure most customs don't care.

A bottle of Selank that lasts ~10 days is like 20 USD. These two the way they work probably mostly relates to more long term changes, or indirect mechanisms where they improve brain function, I'd assume, or at least there shouldn't be any withdrawals beyond at worst returning to baseline. Now I have most confidence to say that about cere because I actually used tons of cere when I had actual benzo PAWS, whereas Selank is more a recent thing, and my baseline now is so good that I maybe can't tell a worsening. But I really don't think Selank produces withdrawals, for me anyway. 


Cere is rather expensive tho, 50 bucks for 5x 10ml (which would be 10 intramuscular doses roughly), but I think the effects actually last a long time once I've taken it for a while. Besides my speech problem Cere also really cleared up my foggy thinking back in the day. These days I take it more occasionally for like 1-2 months every year more for general brain function and I suppose for a modest anti-depressant effect. Also have to inject it, intramuscular injections are rather easy tho, esp. since this stuff is basically like water so you can use very thin (like 25, 26 or 27g needles assuming they are long enough). I've literally used like 1000ml+ of cerebrolysin over the last several years, can't say it has caused me any harm, yet. :) 


I'm not saying I think you should definitely try this stuff, but I just think most supplements that aren't pharmaceuticals suck. (And most pharmaceuticals suck too, but for different reasons.) Tho I don't know if there's anyone else besides me that has had good success with Cere for PAWS from benzos, can't remember anyone. 


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