Ray Peat article on progesterone for seizures - thoughts on using for medication tapering, brain healing

[themartian1000]

I 've done more research about this GABA complex and neurosteroids etc. not just for the fun of it, but it interest me to figure out, because of similar GABA issues with a hypothyroid friend that I am assisting.

How do benzo's alter the GABA sensitivity ? read this
Diazepam-induced loss of inhibitory synapses mediated by PLCδ/ Ca2+/calcineurin signalling downstream of GABAA receptors

How do neurosteroids affect the GABA sensitivity? read this
Physiological role for GABAA receptor desensitization in the induction of long-term potentiation at inhibitory synapses
GABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 h following desensitization of GABAARs in response to agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.

What else influences the GABA complex signaling possible implication for alternative treatment? read these
Co-regulation of GABAA receptors by neurosteroids and protein kinases
GABAA Receptor Phosphorylation and Functional Modulation in Cortical Neurons by a Protein Kinase C-dependent Pathway*

Looks like PKC is an alternative mechanism to gaba regulation with possibility of restorative treatment

Stumbled upon this about licorice root and it reducing glutamate via GABA-B and it's effect on PKC.
Natural Product Isoliquiritigenin Activates GABAB Receptors to Decrease Voltage-Gate Ca2+ Channels and Glutamate Release in Rat Cerebrocortical Nerve Terminals.
Reduction in glutamate release is a key mechanism for neuroprotection and we investigated the effect of isoliquiritigenin (ISL), an active ingredient of Glycyrrhiza with neuroprotective activities, on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). ISL produced a concentration-dependent inhibition of glutamate release and reduced the intraterminal [Ca2+] increase. The inhibition of glutamate release by ISL was prevented after removing extracellular Ca2+ or blocking P/Q-type Ca2+ channels. This inhibition was mediated through the γ-aminobutyric acid type B (GABAB) receptors because ISL was unable to inhibit glutamate release in the presence of baclofen (an GABAB agonist) or CGP3548 (an GABAB antagonist) and docking data revealed that ISL interacted with GABAB receptors. Furthermore, the ISL inhibition of glutamate release was abolished through the inhibition of Gi/o-mediated responses or Gβγ subunits, but not by 8-bromoadenosine 3',5'-cyclic monophosphate or adenylate cyclase inhibition. The ISL inhibition of glutamate release was also abolished through the inhibition of protein kinase C (PKC), and ISL decreased the phosphorylation of PKC. Thus, we inferred that ISL, through GABAB receptor activation and Gβγ-coupled inhibition of P/Q-type Ca2+ channels, suppressed the PKC phosphorylation to cause a decrease in evoked glutamate release at rat cerebrocortical nerve terminals.

Yeah, benzos are honestly just pure evil, and my brain didn't like them. But I'm off 16 months. I am not sure how to use this information to help with healing?

 

[themartian1000]

But wait a minute, were you trying these herbals while also using that synthetic modified GABA pregabalin ?

No, actually I tried anything and everything before resorting to the evil pregabalin, including the jujube. My brain was so wrecked, it needed the nuclear bomb to ease the excitotoxicity. Now the aftermath and clean up must begin...

 

[PeskyPeater]

Yeah, benzos are honestly just pure evil, and my brain didn't like them. But I'm off 16 months. I am not sure how to use this information to help with healing?

Good for you. Benzo's scare me too. I'm taking a certain risk with Etizolam for anxiety, a so called thienodiazepine right now, I find it has mild negative withdrawals.

To help with healing: From my perspective, try too look for a holistic treatment to address those epigenetic changes and don't stare yourself blind on one substance that could be the magic bullet.