An Excellent Explaination of How SSRI's Inhibit Sert

This is a place to post research you have done on the topic along with your conclusions.
MisterCharlie
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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Answers wrote: Mon Dec 13, 2021 6:55 am The question is how do you increase WNT signalling and suppress mir-16?
Dont you mean an upregulation of mir-16? in the locus ceruleus
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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MisterCharlie wrote: Sat Dec 25, 2021 4:55 am 1. From a search: "Melatonin, icariin, and ghrelin, which activate Wnt/β-catenin signaling, have been shown to rescue Ti particle-impaired cellular function in MSCs and MC3T3-E1 cells in vitro"
https://www.researchgate.net/publicatio ... ng_pathway
(doesnt have the full text)

2. Inhibition of GSK3 by lithium, from single molecules to signaling networks
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282483/
I partially fast every day because lack of hunger sensation and it subtly relieves my symptoms. It's rare that my stomach growls. Ghrelin must be suppressed which explains lack of appetite and stomach growling, as ghrelin is released on an empty stomach to induce hunger. This wasn't an issue before crashing.

Lithium would be an interesting substance to explore, as there is one user on here that reports being cured by it. The issue is lithium also increases serotonin, so if you have a severe case of pssd, you risk getting serotonin syndrome. You could mitigate those risks by micro dosing over a long period of time and see if symptoms subtly improve.
Last edited by Tree on Sat Dec 25, 2021 6:06 am, edited 1 time in total.
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

MisterCharlie wrote: Sat Dec 25, 2021 5:06 am
Answers wrote: Mon Dec 13, 2021 6:55 am The question is how do you increase WNT signalling and suppress mir-16?
Dont you mean an upregulation of mir-16? in the locus ceruleus
Most importantly you want to inhibit mir-16 in the dorsal raphe. Coincidentally, the dorsal raphe is part of the brain where 5ht1a pre-synaptic receptors are most abundant. Serotonin seems to be flooded in the raphe from sert loss which desensitizes heteroreceptors and causses these downstream effects in the locus coeruleus.
ytho
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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@Tree

I do have fatigue and some trouble with my memory, but besides that no cognitive problems I’d say. Not sure if that’s considered cognitive, but I have seen a huge loss in my ability to visualize things / scenarios in my mind. Like I could see pictures in my mind with full details and all, but nowadays it’s more a blurry mass when I try to imagine something.
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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ytho wrote: Sun Dec 26, 2021 3:00 pm @Tree

I do have fatigue and some trouble with my memory, but besides that no cognitive problems I’d say. Not sure if that’s considered cognitive, but I have seen a huge loss in my ability to visualize things / scenarios in my mind. Like I could see pictures in my mind with full details and all, but nowadays it’s more a blurry mass when I try to imagine something.
So you don't have any emotional bluntness or lack of pleasure from hobbies? I have the same problem with not being able to visualize. It's like a blank mind feeling. Do you have trouble with your memory? I have trouble recalling information because of foggy brain and less desire/energy to recall information. I'm like a zombie.
ytho
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by ytho »

I do not have emotional bluntness or lack of pleasure from doing things. I feel a bit down because I suffer from PSSD, but PSSD itself is not giving me this lack of enjoyment, if that makes sense. I have some slight memory issues since stopping the SSRI, but not too bad. The foggy brain hits me every other day for a few hours, but in no way 24/7. During those hours I feel very fatigued and my mind goes to crap. The rest of the time, when I’m not foggy / fatigued, my mind / cognition works fine.
MisterCharlie
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by MisterCharlie »

Tree wrote: Sat Dec 25, 2021 6:01 am
MisterCharlie wrote: Sat Dec 25, 2021 5:06 am
Answers wrote: Mon Dec 13, 2021 6:55 am The question is how do you increase WNT signalling and suppress mir-16?
Dont you mean an upregulation of mir-16? in the locus ceruleus
Most importantly you want to inhibit mir-16 in the dorsal raphe. Coincidentally, the dorsal raphe is part of the brain where 5ht1a pre-synaptic receptors are most abundant. Serotonin seems to be flooded in the raphe from sert loss which desensitizes heteroreceptors and causses these downstream effects in the locus coeruleus.
So what drug does that? anything worth testing?
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

ytho wrote: Tue Jan 04, 2022 5:07 am I do not have emotional bluntness or lack of pleasure from doing things. I feel a bit down because I suffer from PSSD, but PSSD itself is not giving me this lack of enjoyment, if that makes sense. I have some slight memory issues since stopping the SSRI, but not too bad. The foggy brain hits me every other day for a few hours, but in no way 24/7. During those hours I feel very fatigued and my mind goes to crap. The rest of the time, when I’m not foggy / fatigued, my mind / cognition works fine.
What are your sexual symptoms and do you consider them severe? It seems to me that genetics play some role in the type and degree of symptoms. Also what was the reason for taking meds? I took ssri for mild depression. I was feeling sad everyday because of past health trauma and being stressed out from college. There are some people on this forum who took ssri's and they weren't even depressed. This could be why some suffer cognitive symptoms and others don't. At the end of the day, though, if you're experiencing persistent withdrawal symptoms, it's most likely caused by sert down-regulation.
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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MisterCharlie wrote: Wed Jan 05, 2022 5:06 pm
Tree wrote: Sat Dec 25, 2021 6:01 am
MisterCharlie wrote: Sat Dec 25, 2021 5:06 am

Dont you mean an upregulation of mir-16? in the locus ceruleus
Most importantly you want to inhibit mir-16 in the dorsal raphe. Coincidentally, the dorsal raphe is part of the brain where 5ht1a pre-synaptic receptors are most abundant. Serotonin seems to be flooded in the raphe from sert loss which desensitizes heteroreceptors and causses these downstream effects in the locus coeruleus.
So what drug does that? anything worth testing?
I'm not sure. There seems to be a few Wnt activators but I don't know if they activate wnt in the raphe. I'm going to microdose zinc then try simvastatin. Lithium is also something that may provide benefits because it's a potent gsk3b Inhibitor. Wnt is activated by gsk3b inhibition.

At this point, I'm desperate for some relief, I've been suffering extreme symptoms for years. This is so fucked up.
MisterCharlie
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by MisterCharlie »

Tree wrote: Sun Jan 09, 2022 10:14 pm
MisterCharlie wrote: Wed Jan 05, 2022 5:06 pm
Tree wrote: Sat Dec 25, 2021 6:01 am

Most importantly you want to inhibit mir-16 in the dorsal raphe. Coincidentally, the dorsal raphe is part of the brain where 5ht1a pre-synaptic receptors are most abundant. Serotonin seems to be flooded in the raphe from sert loss which desensitizes heteroreceptors and causses these downstream effects in the locus coeruleus.
So what drug does that? anything worth testing?
I'm not sure. There seems to be a few Wnt activators but I don't know if they activate wnt in the raphe. I'm going to microdose zinc then try simvastatin. Lithium is also something that may provide benefits because it's a potent gsk3b Inhibitor. Wnt is activated by gsk3b inhibition.

At this point, I'm desperate for some relief, I've been suffering extreme symptoms for years. This is so fucked up.
Antabuse and dapsone for potential lyme disease has been great for me. Might not just be PSSD. For PSSD im trying tianeptine, bacopa, and forskolin which studies show can increase SERT expression.
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