I’d like to share with you all this article I came across. This research demonstrated the effect allopregnenalone has on GABAA receptor gene expression.
jpet.aspetjournals.org/cgi/conte … 303/3/1014
"In addition to potentiating GABAA receptor function, allopregnanolone modulates the expression of genes encoding various GABAA receptor “subunits.”
“Moreover, the changes in GABAA receptor gene expression induced by ganaxolone withdrawal suggest that discontinuation of chronic treatment with this drug may result in a withdrawal syndrome, the severity of which remains to be established with behavioral studies in appropriate animal models.”
…Ganaxolone being the allopregnenalone agonist used in the study. The fact that withdrawl from the agonist (much like, say, an abrupt withdrawl from the steroid itself) caused symtoms of a “withdrawl sydrome” may be telling.
Does this then explain our issue with brain fog? But then what about the fact that finasteride-induced brain fog seems, in many cases, to be irrelersibly long-term? While using the drug, allopregnenalone concentrations must have dropped causing this decrease in GABAA receptor expression. But after discontinuing, you would think receptor densities would have returned to normal.
That is, unless progesterone expression had been altered, perhaps due to the increase caused by finasteride, which in turned resulted in increased corticosteroid concentrations that called for regulation? (Pure conjection though, would need to find research that demonstrates that progesterone expression operates on a negative-feedback loop of some kind)…
So if the problem is GABBA receptor downregulation, then I imagine the solution would be somehow coaxing upregulation to occur. For this, I found evidence that a supplement called Kava might provide the solution. Here’s a citation of a citation:
“Sedative and hypnotic effects: Kavalactones increase GABA receptor density in specific areas of rodent brain (especially hippocampus and amygdala) suggesting GABA-a receptor mediation of the sedative effects of kava, although earlier studies did not find GABA or benzodiazepine receptor binding. German EEG studies have confirmed the limbic structures, especially the amygdylar complex, mediate the sedative effects of kava.”
(Holm E, et al. Arzneimittelforschung 1991 Jul;41(7):673-683.)
And this information was found here: home.caregroup.org/clinical/altm … hystic.htm
So, the mechanism by which finasteride acts decreases allopregnenalone, which in turn reduces expression of GABAA receptor genes. But is this change in receptor density long-term? Is there a way to stimulate receptor gene expression back to previous level (e.g. kava)?