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Upregulating Gaba in the Amygdala?

anxiety amygdala gaba gaba receptors

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#1 Deartothesun

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Posted 20 March 2018 - 02:49 AM


I am wondering if there are any ways to specifically upregulate gaba in the amygdala. I am looking for a more long-term solution to anxiety and a hyperactive HPA axis. So I am not only looking to INCREASE gaba, but maybe the gaba receptors specifically. And I know having a lot of gaba in certain areas of the brain may not be what I want. But the amygdala seems like a good place to start.



The only thing I know of is Kava. I read that Kava upregulated gaba in the amygdala and hippocampus, but the study was done in rodents.




Any input?



#2 BioHacker=Life

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Posted 20 March 2018 - 02:54 AM

flumazenil should do it.


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#3 Deartothesun

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Posted 20 March 2018 - 02:59 AM

Is there any evidence that Flumazenil will do that? I think I understand your rationale for doing it, antagonizing Gaba so that the brain upregulates it. And I am willing to try something like that, even if feels terrible for a short time. But are there any studies on that specifically?


Edit: I know I don't understand this stuff as well as I would like. And taking anything involves risk. I am hoping to increase Gaba receptor density in my amygdala, but not much elsewhere. I am afraid of developing some kind of chronic tiredness and sedation as a result of increased Gaba globally, if that is even a thing...


Edited by Deartothesun, 20 March 2018 - 03:02 AM.


#4 BioHacker=Life

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Posted 20 March 2018 - 03:12 AM

Is there any evidence that Flumazenil will do that? I think I understand your rationale for doing it, antagonizing Gaba so that the brain upregulates it. And I am willing to try something like that, even if feels terrible for a short time. But are there any studies on that specifically?


Edit: I know I don't understand this stuff as well as I would like. And taking anything involves risk. I am hoping to increase Gaba receptor density in my amygdala, but not much elsewhere. I am afraid of developing some kind of chronic tiredness and sedation as a result of increased Gaba globally, if that is even a thing...

 

Well yeah it it upregs and increases receptors.

 

1. https://www.ncbi.nlm...pubmed/16084060

2. https://www.ncbi.nlm...pubmed/15659288

3. https://www.ncbi.nlm...pubmed/15531382

4. https://www.ncbi.nlm...pubmed/18453026

 

It's studied for more PAWS (long term sides of benzo use induced downregulation of receptors) as it reverses the symptoms by re coupling receptors. Also in hyperinsomnia as a cream or sublingual as they have VERY overactive GABA-A receptors. No studies I've seen show any negative sides in non dependent benzo users.


Edited by BioHacker=Life, 20 March 2018 - 03:14 AM.


#5 Galaxyshock

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Posted 21 March 2018 - 04:00 PM

Kava Kava increases GABA-A receptors in the amygdala and hippocampus.



#6 Daniel Cooper

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Posted 21 March 2018 - 06:50 PM

Kava Kava increases GABA-A receptors in the amygdala and hippocampus.

 

 

I've heard this repeated many times, but are there actual studies that back this up?



#7 Deartothesun

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Posted 21 March 2018 - 10:38 PM

 

Kava Kava increases GABA-A receptors in the amygdala and hippocampus.

 

 

I've heard this repeated many times, but are there actual studies that back this up?

 

 

Like I mentioned, I have only seen one study that mentioned this. And it was done in rats.


It's also the only thing I have personally found, period, that supposedly increases Gaba receptors selectively in the limbic system.



#8 Nietzsche

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Posted 22 March 2018 - 10:11 PM

I understand your goal in theory but selectively upregulating GABA in the limbic system is a goal I can't see you achieving to a level of clinical significance. There are many, many clinicians and researchers who wish we had the clinical capacity to change specific receptor properties in specific brain regions. That Kava study on rodents is unconvincing (but there's no harm in trying it, I suppose).

 

But sure, try flumazenil, why the hell not.

 

Long-term changes in anxiety come from cognitive-behavioral interventions, mindfulness training. Some supplements may be useful as well.

 

Sorry, sometimes it's necessary to question the premise of a question in order to give an evidence-based answer.


Edited by Nietzsche, 22 March 2018 - 10:12 PM.

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#9 Deartothesun

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Posted 22 March 2018 - 10:17 PM

I understand your goal in theory but selectively upregulating GABA in the limbic system is a goal I can't see you achieving to a level of clinical significance. There are many, many clinicians and researchers who wish we had the clinical capacity to change specific receptor properties in specific brain regions. That Kava study on rodents is unconvincing (but there's no harm in trying it, I suppose).

 

But sure, try flumazenil, why the hell not.

 

Long-term changes in anxiety come from cognitive-behavioral interventions, mindfulness training. Some supplements may be useful as well.

 

Sorry, sometimes it's necessary to question the premise of a question in order to give an evidence-based answer.

 

I agree. It was just a shot in the dark I guess. Already taking medication and doing therapy. Just began meditating. Been doing the former two for 5 years. The meds seem to have helped the most. But every year or 2 I have to increase the dosage. Right now I am on the max dose of my SSRI (Zoloft) and had to add Buspar. So I'm looking into other, possibly long-term solutions. Hopefully meditation will help. Even began looking into TDCS.

Thanks for your reply.



#10 Nietzsche

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Posted 22 March 2018 - 10:32 PM

Consider looking into low-level laser therapy (LLLT). Its shown promise in multiple psychiatric and neurological conditions. I don't think there's studies on anxiety yet, but it couldn't hurt and you can buy a suitable IR 810nm light on Amazon for $40 or less.


And sometimes switching drugs helps. Viibryd may be a good next choice ... could potentially replace the Zoloft and the buspar.


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#11 Daniel Cooper

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Posted 23 March 2018 - 12:21 AM

Consider looking into low-level laser therapy (LLLT). Its shown promise in multiple psychiatric and neurological conditions. I don't think there's studies on anxiety yet, but it couldn't hurt and you can buy a suitable IR 810nm light on Amazon for $40 or less.


And sometimes switching drugs helps. Viibryd may be a good next choice ... could potentially replace the Zoloft and the buspar.

 

Could you tell us more about LLLT for these applications?  Studies?  How are they applying it?  To the scalp?  Nasal passage?

 

 

 


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#12 Nietzsche

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Posted 24 March 2018 - 08:12 AM

Most studies I'm familiar with are administering it to the scalp. Intranasal is a good option as well (there are some such devices on the market already), but scalp application is logistically easier for clinical research purposes.

 

There have been several promising human studies on LLLT/photobiomodulation in traumatic brain injury, strokes, and at least two that I'm aware of in depression.

 

Two good review papers to get you started:

https://www.ncbi.nlm...les/PMC5066074/

 

https://www.ncbi.nlm...les/PMC4777909/



#13 Nietzsche

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Posted 24 March 2018 - 08:17 AM

And I must something from my first post: I reviewed one of the depression studies, and they did indeed find decreases on anxiety measures as well. So, could be worth a shot.

 

I use it myself for depression and cognitive enhancement using a DMetric IR Illuminator, 810nm, that I bought off Amazon. It seems to do something. There's some topics on it in the Nootropics forum here I think.


Edited by Nietzsche, 24 March 2018 - 08:19 AM.


#14 normalizing

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Posted 12 May 2018 - 04:26 PM

flumazenil is impossible to get unless you overdose on benzos and even then the stupid people at the emergency will probably not even know about it to give it you. i asked my doctor about many types of meds including this one and they dont even know they exist, that is unless you are in europe where they actually know more than the american doctors *face slap*

 

anyway, about kava, it doesnt do shit for me in high doses only causes mild hornyness perhaps related to some of its dopamine influence? just like theanine, same type of function at least in me.

 

im so happy how limited are things that can help with GABAA!!!!!!!!!!



#15 BioHacker=Life

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Posted 17 May 2018 - 02:01 AM

flumazenil is impossible to get unless you overdose on benzos and even then the stupid people at the emergency will probably not even know about it to give it you. i asked my doctor about many types of meds including this one and they dont even know they exist, that is unless you are in europe where they actually know more than the american doctors *face slap*

 

anyway, about kava, it doesnt do shit for me in high doses only causes mild hornyness perhaps related to some of its dopamine influence? just like theanine, same type of function at least in me.

 

im so happy how limited are things that can help with GABAA!!!!!!!!!!

 

Rc companies sell it and I've been using it. 



#16 Daniel Cooper

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Posted 17 May 2018 - 01:51 PM

The problem with flumazenil is that it has very short half life .... about 15 minutes.  My suspicion is that if you want it's NAM properties to upregulate or recouple GABA receptors you really need it in your system nearly continuously.   Aside from an implanted pump I'm not sure how you do that.

 

 

 

 



#17 grubbo

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Posted 19 May 2018 - 01:37 PM

I'm very interested in this too because when I first discovered it about 10 years ago I found clonazepam just the most remarkable, euphoric, life-affirming stuff I've ever come across even at 1mg (which I think is an unusual reaction). These days it hardly seems to do much but sedate, alas even though I haven't taken it regularly for about 5 years. So my tolerance has never reset, yet I know flumazenil has been used successfully for that purpose in cases of epilepsy where they had become tolerant to clonazepam and it wasn't having an anticonvulsant effect anymore. 

 

I think it would be easy enough to knock up a nasal spray, you might have to administer at low doses many times a day for maximum effect, it's not clear. In the study I just mentioned they were using 1.5mg IV flumazenil and although it precipitated a mild withdrawal response there weren't seizures. The paper is interesting (PMID 1670787). 

 

I've read elsewhere that flumazenil is rectally active too. Perhaps a nebulizer could work too.



#18 normalizing

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Posted 19 May 2018 - 05:45 PM

alright, how does one get it though? it seems to be only administered in ER



#19 kurdishfella

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Posted 12 June 2018 - 05:39 PM

allpregnenolone increases GABA-A. So you can take precursors like pregnenolone or Progesterone (progesterone has to be taken orally high dosage since topical very little is converted to allpregnenolone)

There is also a direct precurstor to allpregnenolone called 5a-dhp which works best (pregnenolone > progesterone > 5a-dhp > allpregnenolone).



#20 normalizing

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Posted 13 June 2018 - 04:58 PM

never heard of 5a-dhp



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#21 kurdishfella

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Posted 03 November 2020 - 03:56 AM

too much GABA and CB1 Can be dangerous because it slows down the brain to the point of no excitatory activity which lead to brain stop working and unless quickly increase youll be dead if not immediatly. Too little GABA Can also be dangerous in the amygdala mostly causing seizures

Edited by kurdishfella, 03 November 2020 - 03:57 AM.






Also tagged with one or more of these keywords: anxiety, amygdala, gaba, gaba receptors

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