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Kraken
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So.. I'm guessing a few people here know how unique and amazing it feels to be on Phenibut or Baclofen. Totally different feeling to Alcohol, Benzodiazapines etc since Phenibut and Baclofen are pretty much the only 2 compounds that agonize GABA-B receptors instead of GABA-A. The GABA-A complex consists of Ligand-Gated Ion Channels in which the receptors are considered "ionotropic". The channels open and close allowing inhibitory and excitatory ions and neurotransmitters to enter. The GABA-A complex is focused on "Classic Neurotransmission". The GABA-B complex is completely different. It's activity is related to signalling pathways rather than direct inhibition or excitation from ions and neurotransmitters. The GABA-B complex is "metabotropic" and focused on neuromodulaiton rather than classic neurotransmission. Instead of having Lingand-Gated Ion Channels, the GABAB complex has 7TM-Receptors coupled to G-Proteins. GABA-B receptors are still obviously agonized by GABA itself; Phenibut being Phenyl-Beta-Gammaaminobuteryric Acid; and Baclofen being Beta-4-Chlorophenyl-Gammaaminobuteryric Acid. It seems extremely hard to selectively agonize the GABAB receptors, but weirdly Phenibut and Baclofen do just that, even though they're synthetic drugs which are just modified molecules containing GABA. 99% of medications that are gabaergic, have a strong affinity only to GABA-A, which makes sense considering that the GABA-A complex synthesizes GABA a lot quicker than the B complex, which seems to rely on a determined signalling pathway (with the exception of those 2 drugs). The unmodified form of GABA, if supplemented won't cross the blood brain barrier. However, the Russians made a synthetic form called Picamilon which consists of GABA and Niacin which can cross the blood brain barrier but binds only to the ionotropic receptors in the A complex. Some people may agree that the feeling of having GABA-B receptors agonized is unique and incomparible to standard GABA-A receptor agonism (ie: getting drunk or taking benzos). Phenibut offers almost a complete euphoria, mood lift, without letting you lose control or motivation; and yeah it's very very addicting because it's almost one of a kind. Upon finding the the G-coupled receptors in the GABAB complex depend on a pathway; I looked into how we could possibly induce more GABAB receptor agonism by finding what this pathway is and what can create activity along the pathway to eventually create metabotropic action at the G-coupled protein receptor sites. And what I've found so far is that it all starts in the GUT! It might just be possible to identify microbes that can produce a form of GABA which can be carried to the B complex rather than to the Ion Channel receptors at the GABA-A site. It seems as if the GABA created by the Lactobacillus and Bifidobacterium microbes is involved in Classical Neurotransmission and is needed at the A complex. However, there's a type of bacteria called Bacteroides Fragilis which is speculated to be responsible for creating a relatively unknown molecule called KLE1738, and KLE1738 may be the key molecule needed to create activity between the gut and the GABAB complex. Still need A LOT of time to make more sense of this but from what I see, it seems like we can create GABA in our gut, or atleast some sort of GABAB receptor agonist which is completely selective to the B complex and not A. Meaning, it looks like we might be able to CREATE Phenibut/Baclofen-like substances, endogenously, by our gut, which would pretty much lift mood, allieviate anxiety, depression and general inhibition if we can somehow alter our microbiome from scratch. Firstly making sure that there is a bacteria responsible for creating a molecule that solely modulates GABAB, then determining what that bacteria is, then rearranging our microbiome by first killing off bacteria with an anti-biotic and then redesigning the microbiome to contain significantly more of the bacteria that's responsible for creating the molecule that modulates the Gut-GABAB axis.
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