Hey guys, I have severe PSSD for nearly 2 years now.
My symptoms are similiar to those seen in PFS. Its not just the sexual dysfunction, its cognitive dysfunction, anhedonia, head pressure, too many symptoms to count.
My Theory is that in PSSD there is a increased Allopregnanolone level (in contrast to PFS) leading to constant high GABA signalling (Allopregnanolone is a potent PAM of GABA), this high GABA signalling inhibits glutamate and LTP function aswell as neurogenesis. Its like im on a benzo 24/7.
The brain shifted to a inhibitory dominant type.
Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes (46 fold increase from DHP to allopregnanolone!)
“The efficiency of the enzyme, the ratio of V max to K m, then was calculated. The enzymatic efficiency of rat 3α-HSD, in the conversion from DHP to allopregnanolone, was 3.7 and was 0.003 in the conversion of allopregnanolone to DHP. The enzyme efficiency of the reductive reaction increased ≈46-fold in the presence of fluoxetine. Fluoxetine did not alter the oxidative reaction. Thus, fluoxetine dramatically enhances the efficiency of the enzyme, but only in the conversion of DHP to allopregnanolone.”
There exists a class of so called GAMSAs https://pubmed.ncbi.nlm.nih.gov/26523675/ 1
These would lower GABA signalling by inhibiting the action of the neurosteroids Allopregnanolone and THDOC. https://en.wikipedia.org/wiki/Golexanolone 1
Unfortunately these are RCs and very hard to get.
I wondered if there are other ways to target this high GABA signalling that is blocking. Normal GABA antagonists like flumazenil won’t work in that case as GABA’s activation is coming from the high Allopregnanolone levels.
Maybe one could try to inhibit something upstream,with something like Mifepristone?
Another way I thought of trying was to inhibit 5AR with Zinc or something but that is likely too weak.
The idea was to lower the GABA signalling and simultaneously increase glutamate/LTP/neurogenesis again by using neurotrophic agents like P21 and NSI-189, so once the brain shifts to a more excitatory type the GAMSA will not be needed anymore. Hopefully this would also correct all downstream hormonal changes and make the brain and body respond to hormones again.
Would be grateful for suggestions.
My symptoms are similiar to those seen in PFS. Its not just the sexual dysfunction, its cognitive dysfunction, anhedonia, head pressure, too many symptoms to count.
My Theory is that in PSSD there is a increased Allopregnanolone level (in contrast to PFS) leading to constant high GABA signalling (Allopregnanolone is a potent PAM of GABA), this high GABA signalling inhibits glutamate and LTP function aswell as neurogenesis. Its like im on a benzo 24/7.
The brain shifted to a inhibitory dominant type.
Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes (46 fold increase from DHP to allopregnanolone!)
“The efficiency of the enzyme, the ratio of V max to K m, then was calculated. The enzymatic efficiency of rat 3α-HSD, in the conversion from DHP to allopregnanolone, was 3.7 and was 0.003 in the conversion of allopregnanolone to DHP. The enzyme efficiency of the reductive reaction increased ≈46-fold in the presence of fluoxetine. Fluoxetine did not alter the oxidative reaction. Thus, fluoxetine dramatically enhances the efficiency of the enzyme, but only in the conversion of DHP to allopregnanolone.”
There exists a class of so called GAMSAs https://pubmed.ncbi.nlm.nih.gov/26523675/ 1
These would lower GABA signalling by inhibiting the action of the neurosteroids Allopregnanolone and THDOC. https://en.wikipedia.org/wiki/Golexanolone 1
Unfortunately these are RCs and very hard to get.
I wondered if there are other ways to target this high GABA signalling that is blocking. Normal GABA antagonists like flumazenil won’t work in that case as GABA’s activation is coming from the high Allopregnanolone levels.
Maybe one could try to inhibit something upstream,with something like Mifepristone?
Another way I thought of trying was to inhibit 5AR with Zinc or something but that is likely too weak.
The idea was to lower the GABA signalling and simultaneously increase glutamate/LTP/neurogenesis again by using neurotrophic agents like P21 and NSI-189, so once the brain shifts to a more excitatory type the GAMSA will not be needed anymore. Hopefully this would also correct all downstream hormonal changes and make the brain and body respond to hormones again.
Would be grateful for suggestions.
