I am going to drop a major bomb soon

This is for hypothesis and even educated speculation.
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guacamo
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Re: I am going to drop a major bomb soon

Unread post by guacamo »

Well my libido is not that bad compared to the other people on this forum so i do not know how to approach this subject here, but i also see improvement in libido, not that big compared to the anhedonia improvement though. The thing is i have extensive idea that would explain how pssd happen and why it induces so many symptoms but this is really complex subject and i do not know when i will be able to write about it. It relates mainly to 5-HT1A, 5-HT1B, 5-HT2B receptors, dopamine receptors, glutamate, GABA, cAMP, protein kinase A and hypothalamus. I may write post about some very interesting studies that i have found recently but i will not dig in this particular topic until i connect the dots fully.
Tree
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Re: I am going to drop a major bomb soon

Unread post by Tree »

Simvastatin upregulates sert via Wnt/β-catenin signaling. Ssri's antagonize wnt signaling, which enhances miR-16 and downregulates sert. Anyone here have any experience with Statins? This is something I'd be interested in trying in an attempt to upregulate sert.
Impermanence
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Re: I am going to drop a major bomb soon

Unread post by Impermanence »

Tree wrote: Mon Oct 18, 2021 8:51 pm Simvastatin upregulates sert via Wnt/β-catenin signaling. Ssri's antagonize wnt signaling, which enhances miR-16 and downregulates sert. Anyone here have any experience with Statins? This is something I'd be interested in trying in an attempt to upregulate sert.
Interesting. This is the pleiotropic effect of statins. Could worth to try it. Don't forget to check your hepatic enzyme one month after using it
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garycooper
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Re: I am going to drop a major bomb soon

Unread post by garycooper »

guacamo wrote: Mon Oct 04, 2021 10:54 am Hey i am currently away from the forum, so sorry for late response. It plateau at like 6 while my basal state is 3.5 in terms of anhedonia.
Any update?
Tree
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Re: I am going to drop a major bomb soon

Unread post by Tree »

Impermanence wrote: Tue Oct 19, 2021 2:09 am
Tree wrote: Mon Oct 18, 2021 8:51 pm Simvastatin upregulates sert via Wnt/β-catenin signaling. Ssri's antagonize wnt signaling, which enhances miR-16 and downregulates sert. Anyone here have any experience with Statins? This is something I'd be interested in trying in an attempt to upregulate sert.
Interesting. This is the pleiotropic effect of statins. Could worth to try it. Don't forget to check your hepatic enzyme one month after using it
It's interesting because it may upregulate sert without raising serotonin or interacting with the 5ht1a receptor unlike Berberine or alcohol. Statins also appear to effect sert through the same pathway as ssri's.
anhedonia
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Re: I am going to drop a major bomb soon

Unread post by anhedonia »

I was thinking about this thread for a while now.

My backstory is taking duloxetine for chronic pain, never had depression or anxiety. Switched to duloxetine from taking low doses of amitriptyline for 4 years, this is where I got PSSD. I had normal sexual dysfunction with amitriptyline, but it was fully reversible by stopping the drug for 1-2 days. The interesting thing is that in the first 4 weeks of taking Duloxetine my libido was much higher than with amitriptyline/No meds. Yes, there was ED and the inability to orgasm, but my libido was really high. After 4 weeks libido was gone and stayed gone till today.

After quitting duloxetine I had a period where I had anhedonia, very strong physical+mental fatigue, no emotions. Today I feel totally fine emotionally, but have almost no libido and have ED+numbness. Before antidepressants, I was super sexual as many here were.

I really think the underlying issue (let me say for me in this case) is 5ht1a autoreceptor downregulation. I experimented with buspirone a bit and had spontaneous bursts of libido. Never took it for more than a few days because I'm scared I will screw the receptors even more. But the 5ht1a theory really explains my symptoms, the increase in libido when starting duloxetine (before 5ht1a autoreceptor was downregulated) and the situation I have now where 5ht1a autoreceptors are in a continuing downregulated state.

Is there not the danger that taking buspirone long-term will desensitize the 5ht1a AR even further, worsening our condition?

tl;dr is there any known way to reliably upregulate 5ht1a autoreceptors?
Duloxetine for TMJ Pain
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arahant
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Re: I am going to drop a major bomb soon

Unread post by arahant »

anhedonia wrote: Fri Oct 22, 2021 4:50 pm I was thinking about this thread for a while now.

My backstory is taking duloxetine for chronic pain, never had depression or anxiety. Switched to duloxetine from taking low doses of amitriptyline for 4 years, this is where I got PSSD. I had normal sexual dysfunction with amitriptyline, but it was fully reversible by stopping the drug for 1-2 days. The interesting thing is that in the first 4 weeks of taking Duloxetine my libido was much higher than with amitriptyline/No meds. Yes, there was ED and the inability to orgasm, but my libido was really high. After 4 weeks libido was gone and stayed gone till today.

After quitting duloxetine I had a period where I had anhedonia, very strong physical+mental fatigue, no emotions. Today I feel totally fine emotionally, but have almost no libido and have ED+numbness. Before antidepressants, I was super sexual as many here were.

I really think the underlying issue (let me say for me in this case) is 5ht1a autoreceptor downregulation. I experimented with buspirone a bit and had spontaneous bursts of libido. Never took it for more than a few days because I'm scared I will screw the receptors even more. But the 5ht1a theory really explains my symptoms, the increase in libido when starting duloxetine (before 5ht1a autoreceptor was downregulated) and the situation I have now where 5ht1a autoreceptors are in a continuing downregulated state.

Is there not the danger that taking buspirone long-term will desensitize the 5ht1a AR even further, worsening our condition?

tl;dr is there any known way to reliably upregulate 5ht1a autoreceptors?
I am taking buspirone since 2019, and I have experimented up to 60 mg/day, theorizing is interesting but I was already experiencing continuous improvements when I first read about this "desensitization of 5HT1a", and after reading about it, nocebo tried to bring me to square one but I said, "fuck off". Bottom line, I am still waiting for the "long term doom desensitization even worsening further" but it's been difficult to happen and I have no plans to quit taking it soon.
There's another member here, @alteredhomeostasis that takes it alongside Prozac and has no complaints and I think he has no plans to quit either.
You didn't take it consistently and had "spontaneous bursts of libido", maybe it is already working "as needed" for you. Like the new med Lybridos (buspirone+testosterone) is being tested "as needed" for women with low libido. in this regimen hypothetical desensitization seems even more unlikely
Wellbutrin (2007 - 2018)
Wellbutrin + Sertraline (2015)
Wellbutrin + Ritalin (2016 - 2018)
Wellbutrin + Ritalin + Sertraline (3 months in 2018)
Buspirone (Feb 2019 - Today)
Ritalin + Buspirone (Nov 2019 - today)
anhedonia
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Re: I am going to drop a major bomb soon

Unread post by anhedonia »

Yeah your experience suggests that this desensitization scenario doesn't necessarily have to happen. Additionally, the off-label use of buspirone for sexual dysfunction might mean that your experience is the rule and not the exception. Otherwise, there should be a lot more people taking buspirone (for anxiety, etc.) that suddenly get sexual dysfunction after desensitization.

In line with this, I found a (rat) study that demonstrates buspirone does not desensitize 5ht1a autoreceptors, even though stronger agonists may have this effect.
However, when buspirone, a weak partial agonist at 5-HT1A receptors, was administered chronically for 14 days, 5 or 10 weeks, no desensitization of 5-HT1A autoreceptors was observed (Sharp et al., 1993; Söderpalm et al., 1993).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013794/
Duloxetine for TMJ Pain
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Jaxx
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Re: I am going to drop a major bomb soon

Unread post by Jaxx »

guacamo wrote: Fri Oct 08, 2021 9:16 am Well my libido is not that bad compared to the other people on this forum so i do not know how to approach this subject here, but i also see improvement in libido, not that big compared to the anhedonia improvement though. The thing is i have extensive idea that would explain how pssd happen and why it induces so many symptoms but this is really complex subject and i do not know when i will be able to write about it. It relates mainly to 5-HT1A, 5-HT1B, 5-HT2B receptors, dopamine receptors, glutamate, GABA, cAMP, protein kinase A and hypothalamus. I may write post about some very interesting studies that i have found recently but i will not dig in this particular topic until i connect the dots fully.
Will be interesting to hear more why you mention serotonin syndrome as a risk, also in your other thread (methylfolate and inositol). Dont get me wrong, i appreciate the safe approach but as inositol has been researched in combination with ssri’s i wonder how big the risk is, or if people with pssd are more at risk somehow in your view.
Also, you mentioned some benefits decreased for you. How would this work if desensitization is not the issue?
Impermanence
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Re: I am going to drop a major bomb soon

Unread post by Impermanence »

Guacamo I hope you're fine. I think we were severals/many waiting for your news and promising trial. You were mystery, that was your right but maybe now you could explain a little more what happened for you in your trial and what is your theory about mixing methylfolate and inositol?
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