I think i am close to discovering the cure.

This is for hypothesis and even educated speculation.
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guacamo
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I think i am close to discovering the cure.

Unread post by guacamo »

For the most recent info visit this thread: viewtopic.php?f=20&t=4506

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896866/
https://www.tandfonline.com/doi/abs/10. ... 21.1929732
https://www.uniprot.org/uniprot/P41595
https://en.wikipedia.org/wiki/Calcium_channel
https://en.wikipedia.org/wiki/5-HT2B_receptor
https://link.springer.com/article/10.1007/BF01787021
https://academic.oup.com/icb/article/41/4/1009/2046729
https://journals.plos.org/plosone/artic ... ne.0206986
https://pubmed.ncbi.nlm.nih.gov/16688720/
https://www.jbc.org/article/S0021-9258(19)74306-3/pdf
https://onlinelibrary.wiley.com/doi/ful ... /cns.13634 explain corticoids cure
https://onlinelibrary.wiley.com/doi/ful ... 10.06795.x
https://link.springer.com/article/10.10 ... 20-00569-0
https://www.ncbi.nlm.nih.gov/books/NBK92750/
https://www.nature.com/articles/tpj201124
https://www.tandfonline.com/doi/abs/10. ... 21.1929732
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556207/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539076/
https://web.williams.edu/imput/synapse/pages/IIA1.htm
https://pubmed.ncbi.nlm.nih.gov/24854234/
https://www.hindawi.com/journals/jst/2014/593934/
https://www.ahajournals.org/doi/full/10 ... 0.25714.D9
https://hal.archives-ouvertes.fr/hal-01 ... rt0206.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670669/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381222/
https://pubmed.ncbi.nlm.nih.gov/9760040/
https://pubmed.ncbi.nlm.nih.gov/15629140/
https://journals.physiology.org/doi/ful ... 00006.2016
https://www.sciencedirect.com/science/a ... 3418306225
Last edited by guacamo on Thu Jul 15, 2021 11:45 am, edited 19 times in total.
JakeLawe
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Re: I think i am close to discovering the cure.

Unread post by JakeLawe »

I'll tell you what they have in common: they relieve depression and/or anxiety in some people.
ErgogenicHealth
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Re: I think i am close to discovering the cure.

Unread post by ErgogenicHealth »

What are some probes to HIT/Target 5-HT2B receptor?
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guacamo
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Re: I think i am close to discovering the cure.

Unread post by guacamo »

5-HT2B "Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca2+ ions from intracellular stores (PubMed:8143856, PubMed:8078486, PubMed:8882600, PubMed:18703043, PubMed:23519215, PubMed:28129538)."
Things that induce serotonin release are propagated by calcium influx and exocytosis and this phenomena is mediated by 5-HT2B, so roughly speaking every single of these substances touch 5-HT2B in one way of another. In my thread mentioned in main post i explained how PSSD is mediated by 5-HT2B, and now i found direct connection between it and substances that are involved in cured cases. This is what this post is all about. So to get cured u should for sure take inositol(best option at bed time), either with tramadol, berberine, 5-HTP, or SSRI. I cannot tell you which one is correct right now as i still do my research. The problem is that all of these substances mediate serotonin increase via different pathways. Best SSRI would be the one with the shortest half-life. Inositol dosage should be above 18g. SSRI or other serotonin substances should be added after 3 day preload of inositol. Regardless of the mechanism that is the correct one i must say that i am sad that there is no discussion about my theory that i think is groundbreaking. viewtopic.php?f=20&t=4484 please contribute to this topic, which would help in my research later on.
MindChanger
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Re: I think i am close to discovering the cure.

Unread post by MindChanger »

Hey guacamo.

Your ideas are definitely interesting, I have researched 5HT2B by myself,but I do not agree that it is possible to find one cure for all cases. In addition, every drug that increases serotonin would lead to changes in all serotonin receptors (5HT1A, 5HT1B, 5HT1C..., 5HT2A, 5HT2B, 5HT2C..., 5HT7). For example, 5HT1B can also inhibit serotonin release, 5HT3 is a ion channel.

Anyway, I'd be interested to contact you and discuss several ideas with you closer. That is why I actually created this account.
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guacamo
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Re: I think i am close to discovering the cure.

Unread post by guacamo »

I believe every PSSD shares the same etiology, no matter what SSRI was taken. It is dysfunction of exocytosis in serotonin neurons. presynaptic 5-HT1 receptors 1A, 1B, 1D mediate serotonin inhibition but it is not the cause of PSSD. There is data that states that 5-HT2B (which is also presynaptic autoreceptor) mediates some of the ssri effect. Actually the theory that SSRI lag by few weeks is result of presynaptic 5-HT1A receptors has no scientific data to support it, there is causation but not correlation. Some scientist refuse to believe that their research disproves the thesis they wanted to prove or provides no correlation is very misfortunate, because they bend the data to fit the thesis, but when you tune into the paper and read it from start to finish u can come to conclusion by yourself, let's say they introduce substance A that has pleiotropic function and then atribute it's effect on certain mechanism of the drug without explanation why, because this drug actually works by many different ways and other effects could actually take place. There is no explanation for this gross incompetence. To find paper that is actually done correctly without conflict of interest or confirmation bias or correctly use logic to atribute correlation between different parts of the data is not easy. And when it is done it is very often a paper on specific matter whose autors have deep knowledge on the nervous system. But they more often than not contribute to very special cases, and they have little to no use for our research. There are mutant mices with low expression of 5-HT1A and with high expression of 5-HT1A and effects of SSRIs therapy between them produces not much of a difference. The most actual data about SSRIs mechanism is that they inhibit l-Type VGCCs, because combining it with Ca2+ inhibitors wastly improves the treatment. Other theory says that SSRI works via interaction with g-protein coupled receptors placement, but it is very novel theory and understanding of how this works and why it helps is something that has to be researched more in the future, i do not support this idea anyway. 5-HT2B is involved with IP3, exocytosis and has influence on serotonin transporter (which produces calcium influx via L-Type VGCC too)as well as L-Type VGCC. It fits the mechanism of every cured case, there always was interaction between 5-HT2B and inositol triphospate. SERT interacts with L-Type VGCC. L-Type VGCC interacts with 5-HT2B, 5-HT2B interacts with IP3, IP3 interact VGCCs too, same as mushrooms , mdma, sjw and others.. I do not try to invent the circle again. It is right there between the eyes. That is the only interaction shared by every cured cases. Some people take substances that have affinity for 5-HT1A receptors and are surprised by the effects, either happy or not, but it is like adding water to the barrel that has hole in it.
Last edited by guacamo on Fri Jul 09, 2021 6:36 am, edited 3 times in total.
finities infinities
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Re: I think i am close to discovering the cure.

Unread post by finities infinities »

This is very interesting theory because I have mianserin induced PSSD. And 5ht1a activation, alpha 2 activation or very strong 5ht2 blockade masked this PSSD symptoms, also cholinergic activation, calcium channel blockade masking my PSSD symptoms and induce vasodilation.
I'd love to talk you!
link11
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Re: I think i am close to discovering the cure.

Unread post by link11 »

I took inositol and I'm still paying the price. It's almost made me dyslexic and totally ruined my cognition. Did nothing beneficial for me at all.

It's changed something but I don't know what exactly
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guacamo
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Re: I think i am close to discovering the cure.

Unread post by guacamo »

At what time of the day did u took inositol and how much did u took and for how long? Did u mix it with other supplement or medicine?
Sb919
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Re: I think i am close to discovering the cure.

Unread post by Sb919 »

I am currently on day 6 of 18g inositol. Am taking 9g in the morning and 9g before bed to avoid any potential stomach upset, but haven't experienced that yet. I do feel like it's disrupting my sleep though. Haven't combined with anything other than CBG I have been taking.

Why is it better to take the full dose before sleep? I am considering trying it tonight.

Also how long do you think it should be taken for?
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