We all know that Ethanol alcohol (the type found in beer and other drinks) potentiates GABAergic neurotransmission and inhibitory tone in the central nervous system. The result is intoxication, lack of coordination, slurred speech, general stupidity; we all know the result.

Besides ethanol, you can potentiate GABA by taking GABA supplements, but for me this just puts me in a very calm, almost zombie-like state. Has anyone found GABA supplementation useful at all? What about general GABA potentiation? What other drugs potentiate GABA and what are the effects?

Precursor:
L-Theanine (Gamma Ethyl amino glutamic acid) works pretty well at 400-1,000 mg to induce a calm relaxed yet focused state of mind.

Receptor:
Phenibut 200-1,000 mg works more potently..... not recommended in high doses daily or while driving.

is it possible to target GABA A and GABA B receptors selectively? GABA A receptors are faster in action, whereas GABA B have longer duration and are more modulatory.

GABA A receptors:
(S)-(+)-homo-ß-proline (Homologue of proline. Reported to be a potent agonist at GABAA receptors. Interacts with GABAA-uptake mechanisms. Moderate inhibitor of GABAB receptor binding.)

GABA B receptors:
baclofen
gabapentin (Mimics GABAB receptor activation. )

like most any chemical that involves GABA, phenibut is bad news

http://www.mindandmuscle.net/forum///?act=ST&f=1&t=14199

thanks!

I would disagree GABA is an effective neurochemical to modulate for stress reduction. While there are several ways to effect GABA and certain compounds have to be used carefully (GHB, Phenibut), there are safe ways to use them.

CNS Drug Rev. 2001 Winter;7(4):471-81
Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug.

Lapin I.

Department of Clinical and Experimental Psychopharmacology, Bekhterev's Psychoneurological Institute, Bekhterev Street, 3, St. Petersburg, 193019, Russia. spbinstb@infopro.spb.su

Phenibut (beta-phenyl-gamma-aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA-mimetic, primarily at GABA ( B ) and, to some extent, at GABA ( A ) receptors. It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA), a putative endogenous anxiogenic. The psychopharmacological activity of phenibut is similar to that of baclofen, a p-Cl-derivative of phenibut. This article reviews the structure-activity relationship of phenibut and its derivatives. Emphasis is placed on the importance of the position of the phenyl ring, the role of the carboxyl group, and the activity of optical isomers. Comparison of phenibut with piracetam and diazepam reveals similarities and differences in their pharmacological and clinical effects. Phenibut is widely used in Russia to relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic patients; as well as a pre- or post-operative medication. It is also used in the therapy of disorders characterized by asthenia and depression, as well as in post-traumatic stress, stuttering and vestibular disorders.

it will cause rebounds and withdrawals and your worst nightmere, in some people like me, after a single modest dose. i wouldnt recommend using it daily for a long time and then later discovering it has a severe dependance more than you thought it would have. you can find many phenibut horror stories. it depends on the person so be careful and see if going off it after a short time does anything. i took the modest and supposed non-dependance causing neurontin (GABAPENTIN) for a few days and went off it and i couldnt get off my floor. probably comparable to crack. anyway be careful

Interesting reaction. Phenibut is definitely not my first pick as a compound to effect GABA (Most of what i have heard regarding negative effects is when people were abusing it and taking more than 1G daily).

Personally I find L-Theanine to be quite pleasant.

I notice that you guys talk alot about dosing etc. which frankly I have no idea how you arrive at that information, but anyway, is there any interest in pharmacogenetic typing in relation to dosing?

Experience and research.

In an ideal world but few drug companies are willing to invest.

I don't know about that... Drug companies spend lots of dollas on human studies to get FDA approval.
Have you conducted you own human studies?

But my question relates to genetic variability in pharmacokinetics anyway.

I've been involved in a few and am planning some interesting studies with Nootropics in the future.



What did you think my answer was in regards to?

I was not meaning big pharmaceuticals interest in pharmacogenetics - they are already bringing drugs back they could not get FDA approval on becuase now they can identify in which genographic the drug is efficacious and market it to those.

I was meaning in your area - nootropics. Have you looked into this?

Wow - and your findings?

I have no interest.



Nootropics work what can i say.

have caffeine everyday then quit - youve just potentiated GABA by upregulating GABA receptors with a GABA antagonist

I've tried gaba, theanine and phenibut. I use the phenibut rarely because of the many cautions I've heard regarding it's use. Both it and l theanine are sort of expensive. Gaba is cheap when you buy it in bulk. I've been taking gaba in the evenings as a sleep aid along with theanine sometimes. Are there any contraindications for daily gaba use?

I'm usually don't recommend GABA due to the lack of human studies and poor penetration into the BBB. Phenibut I don't recommend for healthly people as its a pretty potent compound. But I see no problems taking GABA or preferably L-Theanine to boost GABA on a daily basis.

Have you tried Korphedon? It's russian as well and I read it's very powerful, piracetam-like, cyclized GABA molecule (I don't know what that actually means but supposedly it would be fairly easy to manufacture from GABA).

I think Zopiclone targets B receptors, and now has approval for long term use.

Also omega 3 modulates Gaba receptors. I have mixed zopiclone with omega 3 regularly. While i find neither on its own pleasant, The two together are mindblowing. Suggesting this combo to others just results in amused replies. "omega 3, that stuff you buy from the healthstore..titter, titter"...

Anything which goes for Gaba receptors increases demand as the networks are mostly convergent.

The solution to this convergence problem for those in dire need of long term chemical stress management may be to shift between different kinds of Gaba enhancing drugs. that is four weeks on GabaA drugs shifting to four week on GabaB drugs, thereby pushing the receptors to do their own thing on a regular basis.

Of course no drug company would be willing to research, format and sell a treatment which requires moving between one chemical for a period and then another, as it would then result in people deciding to switch brands for the best of either chemical.

Most of the published research on phenibut is in Russian and hence not available to the average Joe Blow. I agree, Phenibut is very strong compound with a reasonably long half-life. A long half-life is typical for most GABAergics.

I have taken it on and off now for perhaps just over a year. For me it's a recreational substance that I use on occasions. Maybe once a month. The largest dosage I have taken is about 4-5 grams. With this amount I didn't really get any negative side effects. I had the usually sound sleep with lucid dreams and woke up on two consecuative days still feeling the phenibut buzz. My mind is pretty sharp and I can still function well even with large dosages.

For me, Phenibut has been nothing but positive