Final theory of PSSD etiology. Get in here!

This is a place to post research you have done on the topic along with your conclusions.
MisterCharlie
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Re: Final theory of PSSD etiology. Get in here!

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https://pubmed.ncbi.nlm.nih.gov/8131066/
Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization
Breathdeep
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Re: Final theory of PSSD etiology. Get in here!

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MisterCharlie wrote: Fri Jan 21, 2022 6:21 pm https://pubmed.ncbi.nlm.nih.gov/8131066/
Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization
Have you tried lithium, sjw or inositol?
If so what did you experience?
Sertraline 2018-2019
Fluoxetine November 2020
Symptoms low libido and ED
also muted emotions
MisterCharlie
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Re: Final theory of PSSD etiology. Get in here!

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Breathdeep wrote: Tue Feb 22, 2022 2:26 pm
MisterCharlie wrote: Fri Jan 21, 2022 6:21 pm https://pubmed.ncbi.nlm.nih.gov/8131066/
Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization
Have you tried lithium, sjw or inositol?
If so what did you experience?
-Myo-Inositol 2 grams increased erections and libido a bit 30-35%, one day after taking it for another couple days after that. Did this for about 4 weeks (for the weekends) and then got nervous after Tree said it would desensitize the 5ht1a receptor over time. Didnt seem to give permanent improvement or worseneing in the time I took it.
-Lithium orotate 4mg made me feel great at first, pleasant feeling mood wise and less anxious- then seemed to make me a little worse (15%?) with libido, erections but that couldve been other things. Not sure what the high/max dose of lithium for pssd would be or whether lithium carbonate is better
-Havent tried SJW for pssd.
MisterCharlie
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Re: Final theory of PSSD etiology. Get in here!

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Any updates or new trials?
aj89
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Re: Final theory of PSSD etiology. Get in here!

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Tree
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Re: Final theory of PSSD etiology. Get in here!

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guacamo wrote: Fri Dec 17, 2021 8:20 am I do not think that taking reboxetine is the way to go. There are two ways of how desensitization works. There is heterologous desensitization where ligand no longer exert cellular response in the receptor. After this happens receptor becomes internalized. This is what i think is happening in PSSD. The other desesensitization is homologous desensitization where signal transduction exerted by the receptor is broken, like serotonin no longer activates G proteins. They both happen in PSSD, but homologous desensitization in this case is a result of heterologous desensitization caused by extreme serotonin levels in the raphe nuclei. So i think logic would tell us that you cannot make 5-HT1A receptor activate g protein no matter how sensitive g proteins are, because it is simply what internalized receptors do. So to make it work right one should work towards making 5-HT1A receptors not be internalized anymore, that would cause the whole cascade to work again. I think no matter how much GIRK antagonist one will take, it wont overcome the fact that 5-HT1A receptor is internalized and will not activate them no matter what. Anyone more interested in the topic i advice to look on this robust paper on GIRK channel
https://scholarscompass.vcu.edu/cgi/vie ... ontext=etd.
The thing is excess PIP2 levels can instead of activating GIRK2 or GIRK3 in 5-HT1A mediated transduction, go and activate Gqs proteins that go on and activate Protein Kinase C that is a direct inhibitor of GIRK channels by inhibiting their affinity for PIP2 , so one can actually inhibit GIRKs by taking inositol instead of activating it. That is something thats need to be overcomed, and in cases where taking inositol helped there could be that in the brains of these people PIP2 went directly to GIRKs instead of activating PKC. I also found a paper which stated that hypericin from st john wort is Protein Kinase C inhibitor, which can contribute to it's anti-anhedonic effect on PSSD. But surely there is something missing, something that needs to be overcomed in order to change the whole chain of cellular effects. But st john wort is not potent enough inhibitor to overcome the inositol mediated PKC activation if that is the case. I did read on the forum that one person stated that drinking wine provides relief of the symptoms, grape contain miyabenol C that inhibits PKC.
Glucocorticoids can also uncouple 5-HT1A autoreceptors by reducing GIRK2 RNA levels. This explains why stress makes pssd symptoms worse. Your theory is backwards. We have less GIRK2 expression and increased pkc activation. Excess pkc activation causes less sert expression and 5ht1a desensitization. Ultimately I believe microRNA changes are responsible for decreased sert expression which leads to GIRK2 decoupling of 5ht1a receptors.
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