An Excellent Explaination of How SSRI's Inhibit Sert

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Integra
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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MisterCharlie wrote: Mon Jan 10, 2022 4:45 pm
Tree wrote: Sun Jan 09, 2022 10:14 pm
MisterCharlie wrote: Wed Jan 05, 2022 5:06 pm

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.
U cured lyme?
MisterCharlie
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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15 years of lyme treatment, off and on. Antabuse and "double dapsone" protocol (dont do at the same time) over the last year were game changers. Start at TINY dosages.
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

MisterCharlie wrote: Mon Jan 10, 2022 4:45 pm
Tree wrote: Sun Jan 09, 2022 10:14 pm
MisterCharlie wrote: Wed Jan 05, 2022 5:06 pm

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.
There are other substances that increase sert but I'm focused on upregulating sert through wnt activation. I believe sert has been permeantly silenced through changes in it's sert mrna transcription.
MisterCharlie
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by MisterCharlie »

Tree wrote: Mon Jan 17, 2022 1:39 am

There are other substances that increase sert but I'm focused on upregulating sert through wnt activation. I believe sert has been permeantly silenced through changes in it's sert mrna transcription.
Trialing tianeptine, bacopa, forskolin for sert. Doing 1500 hcg today since estradial (from testosterone being aromatase'd) has been shown to increase Sert mrna

Still occassionally doing dopamine antagonists (to upregulate), and going to trial Gaba agonists A and B to downregulate inhibitory Gaba.
Any idea for good Gaba A and Gaba B agonists to take frequently? I was thinking 1 gram phenibut for moderate term Gaba A agonism, and have noticed a bit more horniness the next few days after

Love the simvastatin idea, for wnt activation, since statins are also being shown to be antiviral (with the current viral situation going on around the world, its a plus)
MisterCharlie
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by MisterCharlie »

@Tree
This says simvastatin inhibits wnt: https://www.mdpi.com/1420-3049/24/9/1782/htm
"Simvastatin was found to attenuate H2O2-induced human umbilical vein endothelial cells (HUVECs) dysfunction and inhibit the Wnt/β-catenin pathway"
This says simvastain activates wnt: https://app.dimensions.ai/details/publi ... 1120265609
"Western blot analysis further demonstrated that simvastatin promoted the phosphorylation of low‑density lipoprotein receptor‑related protein 6 (LRP6) and activated the Wnt/β‑catenin pathway"

I guess either way, I want to try it, but what do you think Tree?
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

MisterCharlie wrote: Tue Jan 18, 2022 10:48 am @Tree
This says simvastatin inhibits wnt: https://www.mdpi.com/1420-3049/24/9/1782/htm
"Simvastatin was found to attenuate H2O2-induced human umbilical vein endothelial cells (HUVECs) dysfunction and inhibit the Wnt/β-catenin pathway"
This says simvastain activates wnt: https://app.dimensions.ai/details/publi ... 1120265609
"Western blot analysis further demonstrated that simvastatin promoted the phosphorylation of low‑density lipoprotein receptor‑related protein 6 (LRP6) and activated the Wnt/β‑catenin pathway"

I guess either way, I want to try it, but what do you think Tree?
We want to try to activate wnt in the brain, particularly in the dorsal raphe, but can't find anything that does yet. I'm going to microdose simovastin when it arrives which will probably be sometime later this month or February. It activates wnt in the hippocampus so it might activate in the raphe too. Who knows. It's worth a try. "Moreover, simvastatin can promote Wnt/β-catenin signaling in the hippocampus of adult mice, and enhance neurogenesis both in cultured adult neural stem cells and the mouse hippocampus".


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894260/
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

Tree wrote: Wed Jan 19, 2022 3:03 am
MisterCharlie wrote: Tue Jan 18, 2022 10:48 am @Tree
This says simvastatin inhibits wnt: https://www.mdpi.com/1420-3049/24/9/1782/htm
"Simvastatin was found to attenuate H2O2-induced human umbilical vein endothelial cells (HUVECs) dysfunction and inhibit the Wnt/β-catenin pathway"
This says simvastain activates wnt: https://app.dimensions.ai/details/publi ... 1120265609
"Western blot analysis further demonstrated that simvastatin promoted the phosphorylation of low‑density lipoprotein receptor‑related protein 6 (LRP6) and activated the Wnt/β‑catenin pathway"

I guess either way, I want to try it, but what do you think Tree?
We want to try to activate wnt in the brain, particularly in the dorsal raphe, but can't find anything that does yet. I'm going to microdose simovastin when it arrives which will probably be sometime later this month or February. It activates wnt in the hippocampus in mice so it might activate in the raphe too. Who knows. It's worth a try. "Moreover, simvastatin can promote Wnt/β-catenin signaling in the hippocampus of adult mice, and enhance neurogenesis both in cultured adult neural stem cells and the mouse hippocampus".


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894260/
Impermanence
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Impermanence »

MisterCharlie wrote: Mon Jan 17, 2022 4:39 am
Tree wrote: Mon Jan 17, 2022 1:39 am

There are other substances that increase sert but I'm focused on upregulating sert through wnt activation. I believe sert has been permeantly silenced through changes in it's sert mrna transcription.
Trialing tianeptine, bacopa, forskolin for sert. Doing 1500 hcg today since estradial (from testosterone being aromatase'd) has been shown to increase Sert mrna

Still occassionally doing dopamine antagonists (to upregulate), and going to trial Gaba agonists A and B to downregulate inhibitory Gaba.
Any idea for good Gaba A and Gaba B agonists to take frequently? I was thinking 1 gram phenibut for moderate term Gaba A agonism, and have noticed a bit more horniness the next few days after

To potentialise Gaba transmission you could try Topiramate which is an anti épileptique wich help with many conditions (epilepsy, migraine, bipolar disorder, tics...)

Love the simvastatin idea, for wnt activation, since statins are also being shown to be antiviral (with the current viral situation going on around the world, its a plus)
ytho
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by ytho »

Tree wrote: Sun Jan 09, 2022 9:53 pm
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.
Yo, sorry for the late reply, i was off for a few days. My sexual symptoms are missing morning wood or poor rigidity morning wood, loss of spontaneous erections and those that are triggered by visual / though stimulation only, nowadays I’m only able to get an erection through physical stimulation, loss of libido and premature ejaculation.

Are these symptoms severe? I’d say no, not as severe as other peoples symptoms as I’m lucky enough to not have genital numbness. Some lack of pleasure from touching it yes, but by far no numbness. So my symptoms are not severe but still life altering in a very bad way. I used to get erections from thoughts multiple times a day and now I can only get one if I force it up and then it’s weak and fades within seconds if I stop the stimulation.

I took the ssri basically as a trial. Doctor said it might be a mild depressive episode but it later turned out that the cause of my symptoms back then (fatigue, drowsiness, lack of energy) are caused by sleep apnea. So after all, I was never depressed. That’s why I was asked to stop the SSRI. The sleep apnea gets treated by the way.
MisterCharlie
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by MisterCharlie »

Tree wrote: Wed Jan 19, 2022 3:03 am
We want to try to activate wnt in the brain, particularly in the dorsal raphe, but can't find anything that does yet. I'm going to microdose simovastin when it arrives which will probably be sometime later this month or February. It activates wnt in the hippocampus in mice so it might activate in the raphe too. Who knows. It's worth a try. "Moreover, simvastatin can promote Wnt/β-catenin signaling in the hippocampus of adult mice, and enhance neurogenesis both in cultured adult neural stem cells and the mouse hippocampus".


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894260/
Thoughts?

https://pubmed.ncbi.nlm.nih.gov/8131066/
Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization
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