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Increase GABA

gaba

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#1 kurdishfella

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Posted 12 June 2018 - 06:21 PM


what are some supplements that increase GABA? from what I have read GABA is the best way to counteract anxiety correct? I notice there are few different GABA's, A and B etc, which one is the best for stress/anxiety?

 

 

is this description correct? 

There are two types of GABA receptors in your brain: GABA(A) and GABA(B) receptors. GABA(A) receptors generally produce feelings of sedation while GABA(B) receptors are responsible for feelings of relaxation and euphoria. 

 

 


Edited by farshad, 12 June 2018 - 06:36 PM.


#2 kurdishfella

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Posted 15 June 2018 - 06:48 PM

is GABA - A more for CRF1(cortisol releasing hormone 1) and GABA-B is more for CRF2?

 

Supposedly both GABA A & B are anxylotic but in different ways? I take it GABA-A is better for anxiety since benzodiazeines target that.

 

also is it true if you use a high enough dosage on   GABA-A drug it will also upregulate B?


Edited by farshad, 15 June 2018 - 07:05 PM.


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#3 Believer

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Posted 16 June 2018 - 06:38 AM

Low dose pregnenolone is excitatory whereas very high dosage (100mg+) is inhibitory via gaba activity.

Keto diet directly increases glutamate to gaba conversion.

Vitamin B5 has strong gabaergic effects via increasing 5-ar activity.

 

Gaba-b can actually produce a specific schizo anxiety but can also alleviate some specific anxiety like the fear of eye contact in autism which is caused by lack of gaba-b activity.

Gaba a is more inhibitory.


Edited by Believer, 16 June 2018 - 06:40 AM.

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#4 kurdishfella

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Posted 16 June 2018 - 08:15 AM

Low dose pregnenolone is excitatory whereas very high dosage (100mg+) is inhibitory via gaba activity.

Keto diet directly increases glutamate to gaba conversion.

Vitamin B5 has strong gabaergic effects via increasing 5-ar activity.

 

Gaba-b can actually produce a specific schizo anxiety but can also alleviate some specific anxiety like the fear of eye contact in autism which is caused by lack of gaba-b activity.

Gaba a is more inhibitory.

I always wonder what the difference was between GABA A and B.

I assume GABA-A  is better for anxiety since most benzodiazepines act on GABA-A? GABA-B I think decreases fear/make you more confidence, and gaba A decrease anxiety, if that makes sense... that is just my thoughts no proof of it.

 

I have tried Lyrica and phenibut which are agonist on GABA B I think and they did make me relaxed but my Anxiety was still there. But GABA-A I have yet to try increase.

 

I have tried pregnenolone and progesterone, they didnt help with my anxiety for some reason, Im guessing I lack the 5-ar enzyme or something for them to convert into allopregnenolone.  I also read somewhere topical progesterone not much of it is converted to allopregnenolone , so progesterone needs to be taken orally to get that conversion.

I saw a thread on  a forum  about a hormone called 5a-dhp which is supposed   to increase   allopregnenolone which increases GABA-A. So im gonna give that  a shot.

 

On reddit lots of people talk about: theanine,taurine none of which worked for me . picamilion is another but i havent tried. Lots of GABA supplements dont work for me for some reason, I guess they dont work as good as hormones or something so 5a-dhp im hoping works .

 

I know GABA-A indirectly decreases Crh(cortisol releasing hormone) but GABA-B I dont know if it does .

 

I read somewhere that if you use a high dosage on GABA B it will increase GABA a too dont know if thats true.


Edited by farshad, 16 June 2018 - 08:48 AM.

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#5 kurdishfella

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Posted 16 June 2018 - 10:47 AM

If anyone has a huge list of GABA agonists please post below



#6 medievil

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Posted 16 June 2018 - 01:13 PM

Picamilon is gaba tied to a vitamin which crosses the BBB and agonises both GABAA and GABAB, its effects are mild, it anecdotially induces some nootropic type effects.

Phenelzine, a MAOI that has a metabolite which induces reuptake of GABA, supposedly makes it a superior MAOI and highly effective for SA, as it also acts on all other implicated neurotransmitters.

GABOB, also agonises both gaba receptors, is a mild anticonvulsant.

Tiagabine, a gaba reuptake inhibitor, I made a overview of the therapeutic effects it has for the treatment of mental illness.

GHB, acts as a GABAB and GHB receptor agonist, therapeutically used for alcohol addiction, in some people it caused ppl to get addicted to it but the addition of naltrexone took away the addictive rewarding effects according to a few case reports, making it a potential therapeutic drug for a lot of mental illnesses.

Phenibut, feels like a mild version of GHB, anecdotes report potent anxiolytic effects but rapid tolerance occurs and there are hororstories of terrible withdrawal after taking it longer then 3 days, but a few days of baclofen or clonazepam/diazepam abloriates the withdrawal painlessly and easily, according to anecdotes including my own.

Baclofen, lacks the potent anxiolytic effects of GHB and phenibut but works effectively for promoting rational decision making and addiction according to several anecdotes, many anecdotes confirm it completely removes alcohol addiction during taking it, craving and withdrawal making it a painless agent for the treatment of alcoholism, several books are written on it.

Muscimol, is a potent gabaa and gabab agonist with mild hallucinogenic effects.

KAVA KAVA, upregulates GABAB

Magnolia bark, a herb as potent as a low dose of diazepam and according to a anecdote dramatically potentiates phenibut by some mechanism.

Nefiracetam, increases GABA in the brain.

Fasoracetam upregulate GABAB

 

I'm sure I'm forgetting a couple, but this should get your research started.


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#7 medievil

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Posted 16 June 2018 - 01:26 PM

This is my research topic on tiagabine for the treatment of mental illness..



#8 Galaxyshock

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Posted 17 June 2018 - 06:59 AM

Gotu Kola increases GABA biosynthesis through induction of GAD enzyme, and Gotu is also a selective GABA-B agonist.


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#9 kurdishfella

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Posted 17 June 2018 - 05:35 PM

Guys... Which GABA is better for decreasing CRH(cortisol releasing hormone)? I saw these 2 studies but my english is limited I have hard time understanding.

 

GABA B - https://www.ncbi.nlm...pubmed/21236282

 

GABA A - https://www.ncbi.nlm...pubmed/10723009

 

What do they say? should I go for GABA A or B? 



#10 kurdishfella

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Posted 18 June 2018 - 11:36 AM

Would Fasoracetam be a good option to increase GABA-B? Im not sure it increases GABA-B? 

cause i need a better alternative then.


Edited by farshad, 18 June 2018 - 11:38 AM.


#11 Galaxyshock

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Posted 21 June 2018 - 07:52 AM

Magnolia bark, a herb as potent as a low dose of diazepam and according to a anecdote dramatically potentiates phenibut by some mechanism.

 

I didn't notice any significant potentiation of Phenibut from Magnolia bark, but it's pretty decent anxiolytic herb.

 

Licorice on the other hand may potentiate PB as it seems to contain a GABA-B modulator:

https://www.ncbi.nlm...pubmed/18495107

 

A teaspoon of Licorice extract gets me a bit high, but this could also be through other mechanisms.



#12 Nate-2004

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Posted 22 June 2018 - 06:54 PM

I've done a lot of reading about both GABA and glutamate lately. So far there aren't any GRAS supplements being sold that boost GABA levels specifically, not without also boosting glutamate, taurine for example. There are a number of ways to boost GAD, i.e. Gabapentin, which can help boost GABA indirectly, though this may not have the effect you're looking for depending on what you're aiming at. 

 

 

There's a list in Table 1 of this pharmacological review on essential tremor, a glutamate/GABA related condition, here's a direct link:

 

https://www.ncbi.nlm...port=objectonly

 

 

 


Edited by Nate-2004, 22 June 2018 - 06:55 PM.


#13 Daniel Cooper

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Posted 26 June 2018 - 03:13 PM

Vagus Nerve Stimulation seems to increase GABAA receptor density in drug resistant partial epilepsy:   

 

 

https://www.research...artial_epilepsy

 

Now, this study is of implantable vagus nerve stimulators, but one might surmise that a similar effect is possible with transcutaneous vagus nerve stimulation (tvns).  

 

Implantable VNS patients have reported decreased anxiety and remission of seizures even after the stimulator was turned off or removed, so the increase in GABA receptor density may be persistent.  

 

I would think this would be relevant to both anxiety and essential tremor.

 

 

 

 

 


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#14 Rocket

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Posted 29 June 2018 - 10:48 PM

I think it's time you change your name to Robert Rackstraw!  :)


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#15 Daniel Cooper

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Posted 30 June 2018 - 01:56 AM

Shhhhhh!   ;)



#16 Galaxyshock

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Posted 02 June 2023 - 10:51 AM

Tiagabine, a gaba reuptake inhibitor, I made a overview of the therapeutic effects it has for the treatment of mental illness.

 

I would like to see that overview. I'm interested in Tiagabine as possibly sustainable anxiety treatment if my anxiety doesn't respond to the current things I have in mind. But Tiagabine seems to have similar side effects as benzos like memory impairment and somnolence? So is it any better than taking Lorazepam regularly?


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#17 gamesguru

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Posted 03 June 2023 - 02:26 AM

GABAB receptors are up-regulated by chronic treatment with lithium or carbamazepine. GABA hypothesis of affective disorders?
https://www.scienced...014299989906870

 

It's available in ionic liquid form on the US Amazon site. It has a mild sedating effect, best taken a few nights a week at 1/4 to 1/3 of the 500 mcg dose. It also modulates (mildly down-regulates) glutamate & dopamine function. But has mitochondrial boosting properties, so can also have stimulating undertones. A lot of evidence around its neuroprotective properties. A lot of studies on low-dose lithium, and different forms even.

 

Besides cobalt and molybdenum (and possibly vanadium) it's the least abundant essential trace mineral in the human body ( see: https://en.wikipedia..._the_human_body ). According to the wiki page, it's used by enzymes and hormone pathways. I find the recommended dose too high, but in small amounts it is very calming almost like an adaptogen.

 

Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual conditioned fear
https://www.scienced...014299914007857


Edited by gamesguru, 03 June 2023 - 02:51 AM.


#18 Galaxyshock

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Posted 03 June 2023 - 10:23 AM

Interesting finding. Anything that upregulates GABA-B sounds good to me. Lithium Orotate is the form sold as supplement, is it effective?

 

I wonder if any pharmaceutical increases the biosynthesis of GABA. I think that would be the best way for purely increasing GABA levels instead of agonizing or modulating the receptors.

 

Hmm then there's Passion flower which I believe inhibits GABA transaminase (GABA-degrading enzyme) activity. 



#19 gamesguru

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Posted 03 June 2023 - 01:31 PM

Interesting finding. Anything that upregulates GABA-B sounds good to me. Lithium Orotate is the form sold as supplement, is it effective?

 

I wonder if any pharmaceutical increases the biosynthesis of GABA. I think that would be the best way for purely increasing GABA levels instead of agonizing or modulating the receptors.

 

Hmm then there's Passion flower which I believe inhibits GABA transaminase (GABA-degrading enzyme) activity. 

 

Yes, I think the orotate form works similar to ionic/elemental lithium. Again, don't get caught thinking more is better. Lithium is a potent one, and I'm not sure about SNRI interactions. In orotate form, 1.25 mg two nights a week will do you well to start.

 

According to Science Guy you want to upregulate receptors, not ligand. If you increase GABA neurotransmitter long-term, you only decrease receptor levels which causes the feedback loop at the presynaptic site which we know so well as tolerance and addiction. Kava is the obvious suggestion that everyone knows, which is supposed to increase receptor levels, but which is still regulated in your country. Then there's magnesium which has a complicated set of mechanisms which we don't understand[ https://www.reddit.c...gaba_receptors/ ], but which seem to avoid the issue of classical tolerance.

 

So if you're going to up-regulate GABA biosynthesis, it needs to be in a very mild way, or only one which compensates for the deficiency of some co-factors, rather than consistently boosting to supraphysiologic doses.

 

Rosmarinic acid inhibits GABA breakdown, so it's similar.  I tried the LEF extract back in the day, and while it was definitely psychoactive and unique in terms of effects, I immediately also knew it was not something that could be used on a daily basis (at least for me).

 

I found something that upregulates glutamate decarboxylase (GAD65), apparently it's pinellia. But again, I doubt this would actually help long-term. And the dose required seems to be large.

https://www.research..._Epileptic_Rats

 

Compared with the epilepsy group, PTA increased the levels of GABA (both doses P<0.01) and GAD65 (mRNA, 800 mg/kg, P<0.01), and suppressed the levels of GAT-1 (mRNA, 800 mg/kg, P<0.01; 400 mg/kg, P<0.05), GABA-T (mRNA, both doses P<0.01), and GABAAR δ subunit (protein, 800 mg/kg, P<0.05) and γ2 subunit (protein, both doses P<0.01).

 

 

Interestingly, I also found this about a reversible MAO-B inhibitor potentially normalizing GABA better. It might also explain why so many people taking selegiline on the DAILY are reporting a negative change in response around the 2nd week, and may need to back off a bit.

 

Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer’s disease

Monoamine oxidase–B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer’s disease (AD) because of its association with aberrant γ-aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC50 = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.



#20 Galaxyshock

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Posted 03 June 2023 - 02:18 PM

According to Science Guy you want to upregulate receptors, not ligand.

 

Well according to Science Guy, chamomile is as bad as benzos when it comes to the GABA system. I know he means well but in my opinion the GABA system isn't THAT delicate that you can't give it a little boost without getting in trouble. Yes I've bombed my GABA receptors with alcohol and Phenibut - and experienced bad withdrawals, but saying things like GABAergic herbs being as bad as benzos is just nonsense.

 

Looks like Pregabalin increases GABA biosynthesis:

 

However,pregabalin has been found to produce a dose-dependent increase in the brain expression of L-glutamic acid decarboxylase (GAD), the enzyme responsible for synthesizing GABA, and hence may have some indirect GABAergic effects by increasing GABA levels in the brain.[80][81][82]

→ source (external link)

 

I've tried Pregabalin couple of times and liked the anxiolysis, it helped with public speaking. But this drug is something that can lead to addiction/tolerance/withdrawals.



#21 gamesguru

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Posted 03 June 2023 - 03:58 PM

Yes but I think there's truth to them only working short term. If you take, say valerian, for anxiety.. it's just going to cause tolerance and rebound anxiety. This is documented for many of the herbs and compounds he calls out in his thread.



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#22 Galaxyshock

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Posted 03 June 2023 - 04:35 PM

Yes but I think there's truth to them only working short term. If you take, say valerian, for anxiety.. it's just going to cause tolerance and rebound anxiety. This is documented for many of the herbs and compounds he calls out in his thread.

 

Some caution is surely adviced if taking them for long term. Personally I've managed to mega-dose things like Gotu Kola and Valerian even for somewhat long time periods without ever feeling a thing when it comes to withdrawals. Tolerance does develope and at some point I kinda just start to feel like stop taking them and switch to something else. If these GABAergic herbs were getting people into trouble, well, they would be banned at least in Finland  :laugh:


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