My theory - Etiology of PSSD and potential treatment.

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guacamo
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Re: My theory - Etiology of PSSD and potential treatment.

Unread post by guacamo »

2000mg of magnesium l-threonate contains more or less 150mg of elemental magnesium.
Meso wrote: Sat Jul 17, 2021 3:36 pm
guacamo wrote: Sat Jul 17, 2021 7:46 am In inositol metabolism and Ca2+ signaling.
I don't think it's that simple. You are onto something here for sure, but it's not the only root issue. There are several factors we must consider. Sex hormone receptors are methylated/silenced. I keep seeing people with normal testosterone levels yet they lack nocturnal erections and morning wood. Also, the genital numbness might be peripheral; a problem affecting the spinal cord, I reckon.

Either way, the only way we can know whether your hypothesis is solid is through good ol` trial and error. I appreciate the fact that you are trying this on yourself. Thank you for that. I always try things on myself to share with other members my reactions before they try it themselves.

That said, several of my patients have found relief with supraphysiological TRT + lithium + progesterone, through trial-and-error, which points towards methylation and sex hormone receptors' malfunction.
I can say as a fun fact that when i reinstate SSRIs after not taking them for quite long time, i have window for like week or two, after which i go worse than my natural baseline, but i if i add inositol, like 50g a day, then i bounce back from crash to the window again. How long would it last i do not know, i suppose it just temporary increases PLC and Ca+2 signaling similar to the way fluoxetine did in the scientific work i linked on my original post.


@edit
It's my fifth day so far, nothing interesting to report as of now. Pay attention to the fact that inositol on average took like 7 weeks to fully work.

#edit
Actually after more research i do not know if SSRI microdose with inositol trial would be more hopeful, i will do more research and come to decision if magnesium trial has to wait after summer and during summer i may try microdose SSRI with inositol, so far with magnesium there is nothing happening, nothing interesting to report, except the fact that i do not have extreme brain fog as i would have, if i took magnesium solo, it is still 5 day though. But initial response to SSRI+inositol was better. So i will try this and come to magnesium later, if this trial will not work. SSRI regulate https://en.wikipedia.org/wiki/SOC_channels function and they are responsible for Ca+2 reuptake, i am curious what will happen if during SSRI-mediated SOCS blockade i will increase cytosol Ca2+ from phospholipase mediated IP3 and RyR3 receptor stimulation. This trial will last 3 weeks, after which i will make an assessment and decide what to do.

Magnesium hypothesis comes from the idea that i tried to interconnect some of the inositol cures with component that is possible to be shared with those group of people who got cured from it, the decision comes from the proposition that what might vary between people is plasma level of various vitamins and minerals, then i researched various substances from that group to find if any of them has any interaction with IP3, DAG or intracellular Ca2+, after research i found that magnesium undergoes various interactions with both IP3 and Ca+2, but it was just a speculation, what was shared with these inositol cures is in fact that in cases where it cured PSSD, inositol was introduced with supplements that either raise serotonin levels, inhibit serotonin reuptake or induce serotonin release, so after extended research i came to conclusion that supplementing with SSRI is more hopefull way to go, as in one of the cured case it was supplemented alongside tramadol, which one of the mechanism is that it inhibits serotonin reuptake. I will write about ongoing sensual experiences during this treatment in this thread on a weekly basis. What is important that my PSSD manifest mainly in anhedonia and lack of emotions and imagination, i thought at some point it is actually my natural state of being, but after reinstating SSRI i experienced 100% relief in those symptoms for a brief moment, before things plateu and i got stuck with those symptoms again, which pointed me that in fact these things come from the fact that i have taken SSRI in the past.
ryjoseph97
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Re: My theory - Etiology of PSSD and potential treatment.

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guacamo wrote: Wed Jul 14, 2021 5:18 pm For what it's worth i will do my trial with l threonate version and we may compare the results, if my way will work and your won't then you may just switch to l-threonate and everything will be fine. Did you take magnesium with inositol? And the second thing is did you experience brain fog?
I switched to Magnesium Glycinate after I saw your post. It's been about a week now. I'll keep you posted. I'm also stacking Lecithin, iron, probiotics, and SJW. I've had a few windows free of depression, including today.
lastround360
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Re: My theory - Etiology of PSSD and potential treatment.

Unread post by lastround360 »

guacamo wrote: Sun Jul 18, 2021 5:04 am inositol was introduced with supplements that either raise serotonin levels, inhibit serotonin reuptake or induce serotonin release
Do you think a serotonin agonist would work since they give the effect of raised seratonin levels? I read somebody cured their PSSD using inositol and a shroom trip. I know psilocybin is a pretty powerful 5HT2A agonist and I have experience microdosing it.
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guacamo
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Re: My theory - Etiology of PSSD and potential treatment.

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I really do not know, all i know that in cases where inositol cured PSSD it was stacked with other supplements that affect in one way or another serotonin.
ErgogenicHealth
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Re: My theory - Etiology of PSSD and potential treatment.

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Male rats lacking the serotonin transporter (SERT–/–) display a robust genotype that has a lower basal ejaculatory performance than wildtype rats (SERT+/+) or heterozygous serotonin transporter knockout (SERT+/–) rats (Chan et al., 2011; Esquivel-Franco et al., 2018). More specific, due to the lack of the serotonin transporter SERT–/– rats have a nine-fold increase in extracellular 5-HT levels (Homberg et al., 2007), decreased number of ejaculations and an increased ejaculation latency (Chan et al., 2011) compared to SERT+/+ rats.
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guacamo
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Re: My theory - Etiology of PSSD and potential treatment.

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Such drastic intervention as removing SERT has to result in broad changes of behavior, including sexual ones. However i do not believe that this is correlated directly with our case.
I believe in calcium (Ca2+) theory because it is involved in every case cured case, it explains certain phenomenas like SSRIs reinstatement relief, it is researched and it is known that SSRIs work via 5-HT2B receptor, this theory does not have holes in it like 5-HT1A theory, which not only does not explain certain phenomenas but also contradicts them, which is illogical.

About 5-HT2B it comes like this: serotonin connects with it's receptor 5-HT2B, which then activates phospholipase C, which creates inositol 1,4,5-trisphosphate (IP3) and and diacylglycerol (DAG) from phosphatidylinositol 4,5-bisphosphate (PIP2). Lithium that some people benefit works via blocking Inositol phosphate-phosphatase, which can result in accumulation of IP3, the research here provided mixed results hovewer, so it's hard to state definite answer. "Either inositol supplementation or inhibition of inositol monophosphatase leading to inositol depletion can, concomitantly, result in IP3 accumulation." https://www.nature.com/articles/tp2016217

IP3 goes to connect with IP3 receptor inside cell, which causes eflux of calcium from endoplasmic reticulum into cytosol, where it performs various functions including exocytosis of serotonin and dopamine etc, even d-serine that is necessary for activation of NMDA receptor, this process is interrupted with SSRIs.

Ca+2 that goes outside the cell is reabsorbed by store-operated channels(SOCS), but SOCS are downregulated during SSRIs treatment.

Then you have action potential when Ca+2 connects with L-Type calcium channel CaV1.2 subtype, channel that is blocked during taking SSRIs, i think this hovewer is less important than the previous statements, i may be in wrong here thinking that though.

It is possible that not one but few of these mechanisms is what SSRIs is all about. It is basically astrocytes in the brain are in shut-down mode because they do not have the tolls that are necessary for them to function. Taking serotonin precursor end up with a crash, but it is not the opposite of relief crash where all the symptoms have increased, it is other type of crash where you feel like shit but it is not inverse version of window neurobiologicaly speaking. What do i mean is that PSSD symptoms let's say can be increased by taking antipsychotics, but it does not mean that PSSD is about dopamine neurotransmission, it's just that blocking dopamine will always induce sexual problems, the same is with taking serotonin precursors, this is not inverse version of window, it's just that increasing serotonin via taking precursor usually ends up with sexual problems and laziness and it's normal, it does not mean that purely increased serotonin is the whole problem, one has to have introspection to sense it and understand what i am talking about. i know i need to understand the whole process on deeper level to understand why some people got cured and others did not. But some of the things that would be helpful to know are only disputed, and research about them is ongoing. The other troubling point is because the cases written long ago have limited amount of information, it is hard to extrapolate anything they wrote for our benefit, these people no longer are a part of community and contact with them is impossible, therefore all we have is but a few pages of information and the end result that it helped.
ryjoseph97
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Re: My theory - Etiology of PSSD and potential treatment.

Unread post by ryjoseph97 »

Is it possible that trpm7 is simply deficient and not malfunctional? I ask because, if that were the case, perhaps a trpm7 agonist could be helpful. There is a list of them in this study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276914/.
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guacamo
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Re: My theory - Etiology of PSSD and potential treatment.

Unread post by guacamo »

Do not take TRPM7 theory as an absolute fact. I wrote how i did came to this conclusion, added by the fact that i messaged the person from reddit who got cured by inositol https://www.reddit.com/r/PSSD/comments/ ... _inositol/
and he wrote to me that he combined it with magnesium, but as you can see it was more or less speculative compared to the Ca2+ theory that was based on solid research. TRPM7 needs magnesium to be expressed, I do not know if agonist would be helpful here if protein expression is already low, due to low intracellular magnesium.
scripy3
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Re: My theory - Etiology of PSSD and potential treatment.

Unread post by scripy3 »

You are onto something. When i go on low calcium diet it complete erases all of mine PSSD and get very high sexual like before PSSD. But only works when vitamin d is medium or low and is not lasting.
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