Glutamate as a possible precursor for GABA in the brain?

[Limpet_Chicken]

I read a couple of publications a while back, that experimented (in rats/mice, can't remember which) that showed that GABA itself DID cross the BBB, but only in tiny, tiny quantities of a few percent. They were experimenting on GABA esters coupled to long-chain fatty acids as esters as potential anaesthetics/anti=anxiety agents, some of which did indeed cross over in significant amounts (I.e sufficient to produce a LD:50 measurement) and found that at least a few percent of enterally/parenterally administered GABA itself did indeed cross the BBB. Not much, but some.

I imagine, given the reports of oral GABA use, that the seemingly anxiogenic effect of activation of peripheral GABA receptors (anecdotal reports from users) might well counteract any anxiolytic effect of activation of central GABAaRs.

Add to that the efflux demonstrated in the cited reviews, that 3H-GABA gets pumped right out again quite quickly via efflux pumps when microinjection of tritiated GABA is done into rat brains, radioactivity is demonstrated with a fairly fast excretion into the periphery, I can't see how GABA (per os) will do much.

 

[ebola?]

ebola, ive also read GABA does not cross BBB but many people who have taken it do comment on being more relaxed.

The brain is closely linked to the body, so certain psychological expectations coupled with sensations of peripheral activity can create feedback loops that fulfill expectations of pharmacological effect.

but you dont give a shit about personal experience type of arguments

I "give a shit about them" insofar as they are used to undergird an argument of scope appropriate to the evidence.

how come it still sells for all those years and people i talked to, or reviews i read claim it does work in combinations or different ways of taking it like sublingual ?

The placebo effect can be very strong and multifaceted, especially when it comes to anxiolysis. Hell, I've gotten clearly discernible, neon geometric visuals from placebo effect alone before.

ebola

 

[asecin]

ebola?, you are absolutely 100% positive GABA doesnt work at all ? even if done sublingual (as most reported its effects) or what about IV ? or, i have read some journals claiming GABA can be adjusted or coupled with other molecules in order to get passed by BBB, im sure there is such occurrences right ? im just mind blown its absolutely useless to ever take GABA for anything. what do you take in place of GABA that affects GABA receptors then ? im not speaking of benzos or alcohol, something besides those ??

 

[Alcyone]

^ GHB, GBL, gabapentin, pregabalin, picamilon, phenibut, baclofen?

 

[sekio]

I'm amazed that people take GABA but they actively avoid MSG. I mean, think about it. The two are the same damn thing except ones got an amine on it and one has a sodium ion.

I'm with ebola on this one, the placebeo effect is strong indeed.

 

[ebola?]

ebola?, you are absolutely 100% positive GABA doesnt work at all ? even if done sublingual (as most reported its effects) or what about IV ?

Route of admin will not affect BBB penetration. Look over Limpet Chicken's post...any central effects of GABA will be extremely minor.

or, i have read some journals claiming GABA can be adjusted or coupled with other molecules in order to get passed by BBB

Then it is no longer GABA.

what do you take in place of GABA that affects GABA receptors then ?

Any GABA agonist, direct or indirect. Gabapentin and pregabalin also affect the character of endogenous synthesis of GABA.

ebola

 

[Renz Envy]

With OP's logic, it seems as if taking a stimulant (which raises glutamate levels) would cause a greater production of GABA, yet stimulant abuse can cause anxiety in individuals. With the example being a burnt-out methamphetamine user. While the cause of their anxiety may be through a different cause, it would not make sense, in my opinion, to theorize that increased glutamate can lead to GABA production.

Because glutamate is the primary excititory neurotransmitter, raising levels of intracerebral glutamate with the goal of increasing levels of gaba is counterproductive. Also, there are likely other bottlenecks to increased intersynaptic gaba than available precursor.

ebola

Makes sense to me

 

[asecin]

^ GHB, GBL, gabapentin, pregabalin, picamilon, phenibut, baclofen?

all RX pills that i dont want or have limited ability to get. i was asking for natural sources that can affect GABA, beyond most popular natural component alcohol. :s

 

[asecin]

I'm amazed that people take GABA but they actively avoid MSG. I mean, think about it. The two are the same damn thing except ones got an amine on it and one has a sodium ion.

I'm with ebola on this one, the placebeo effect is strong indeed.

yeh but such minor changes can alter a lot. ive witnessed it in lots of molecules that look exactly the same but do not have same affects. not that ive studied much chemistry but i have been checking all molecules i have tried and noticed such extreme minor changes can alter things for better or worse do not really understand why.

but what i have to say is, if placebo affect is so strong then i guess discussing pills, producing them and taking them is useless. you can always imagine it works if you just chug juice full of sugar.

 

[Renz Envy]

Valerian root, phenibut

 

[asecin]

dunno why but valerian root does nothing for me. i will take grams of standardized extract, still wtf.

 

[ebola?]

all RX pills that i dont want or have limited ability to get. i was asking for natural sources that can affect GABA, beyond most popular natural component alcohol. :s

Phenibut may be readily ordered as a supplement, and baclofen and gabapentin are unscheduled, and thus easily ordered.

ebola

 

[asecin]

Phenibut may be readily ordered as a supplement, and baclofen and gabapentin are unscheduled, and thus easily ordered.

ebola

i dont recomend baclofen to anyone. few years back i made a thread of me taking it and it almost killed me. do not mix it with even little alcohol, and withdrawl is severe.

 

[Alcyone]

all RX pills that i dont want or have limited ability to get. i was asking for natural sources that can affect GABA, beyond most popular natural component alcohol. :s

Boy, are you hard to please.

 

[dip12]

What do you take instead of GABA that effects GABA receptors then?

If in doubt NOTHING....there are MANY gabaergic drugs with MANY different mechanism of actions - i.e you can't group them together or be in a state of "requiring a drug effecting gaba". You might require an anxiolytic, a sedative, a hypnotic, a muscle relaxant etc etc...but more likely than not you will require NOTHING.

but what i have to say is, if placebo affect is so strong then i guess discussing pills, producing them and taking them is useless. you can always imagine it works if you just chug juice full of sugar.

Because the placebo response will only happen in approx 30% of patients (actual figure can vary) meaning 70% will NOT get an effect. Importantly however without KNOWING who the responders are you, me, the neighbour are all equally potentially susceptible to strong placebo responses. If you tried marketing a sugar pill as pain relief then likely more people than not in a population would identify it as false (also clever LCMS, GCMS, NMR would verify this) resulting in a backlash....or at best (say for example if you decided to create your own brand of false made up physics alongside placebo distribution) you could create your own homeopathic medicine. Also 'you can always imagine it works' doesn't work - why? You can't give yourself a placebo - unless somehow you can erase the memory of ever knowing it was/is a placebo.


This is one of the most peculiar threads in ADD. **adds teaspoon of salt to drink for my hypernatraemia**!!8( (a joke just to confirm!)