How does serotonin inhibit sexuality exactly?

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Jaxx
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Jaxx »

taarn wrote:
Blueturtle wrote:@ Taarn

Yes that seems to be the case, I have heard of people getting PSSD like symptoms from 5-htp and MDMA.


That makes sense try to boost the prosexual stuff rather then try to make your system “less bad” for sex.

Wellbutrin gave me a 40% recovery I’d say I responded more to sexual stimuli and actually felt pleasure but it was still far from what I remembered and the effect wore off.

Have you had success with a particular regiment taarn?
I've tried many things so far but haven't found a regimen that works sustainably to treat sexual dysfunction. Wellbutrin was the best for for sexual dysfunction symptoms, it also helped with emotions. But I only retained the emotional improvements. Dopamine agonists were totally useless btw.

BPC-157 and CDP-Choline were good for cognitive issues and brain fog, I would say 100% relief in this regard. BPC also helped with my mood.

Ipamorelin + Mod-GRF 1-29 helped with sleep and regeneration. My sleep is quite acceptable now. Although anxiety and OCD disappeared when I got PSSD, my sleep was far from perfect and I happened to have issues.
I'm also taking Forskolin daily, I feel it gives me more energy.

These were the most helpful to date, but I will create a detailed log thread soon.
I'm still waiting for meds and some chemicals to arrive, I still have to do a lot of experimenting. I will also meet my psych soon and also a neurologist so I will try to get some prescriptions.

What I think (and hope) to work as a sustainable treatment regimen is the following:
1.) An acetylcholinesterase inhibitor: Donepezil, Rivastigmine or Galantamine
2.) Something to boost tonic dopamine: Rasagiline or Amantadine
3.) Something anti-serotonergic: Metergoline or Ketanserin

I'm still thinking on how to avoid tolerance or desensitization. Likely I will incorporate some Memantine but it's also possible Amantadine don't have such issues with tolerance. I'm also thinking about adding NAC to the regimen but I'm afraid of the glutamate transporter upregulation, I have to research that a bit more.
Any thoughts on Tianeptine? Ive read some contradictive stuff if it really decreases serotonin.
taarn
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Re: How does serotonin inhibit sexuality exactly?

Unread post by taarn »

Jaxx wrote:Any thoughts on Tianeptine? Ive read some contradictive stuff if it really decreases serotonin.
First I also found Tianeptine as interesting but I've also read contradicting stuff. But finally I thought I won't be tinkering with it. If I remember well it enhances SERT binding but can decrease SERT mRNA expression. It also does something like making dopamine receptors more sensitive.

I haven't found anything good to decrease central serotonin. Probably beta-alanine has such effect but I think it's very mild.
If you want to increase/enhance SERT your best bet is Evodiamine and Forskolin, as far as my knowledge goes. Bacopa is also an option but it has more serotonergic effects which I'm not sure are good.

Increasing BDNF can be useful too. (https://www.ncbi.nlm.nih.gov/pubmed/18474368)
Alazocine (SKF-10047) which is a sigma-1 agonist also has the ability to increase serotonin reuptake by SERT.

And there are the TPH inhibitors like Fenclonine and a few others. If you want to do some manipulation with serotonin receptors with the goal of reversing PSSD and getting out of the current bad homeostasis, I think a TPH inhibitor can be useful. The best would be to permanently enhance SERT function, we would need to trial this more. Forskolin and Evodiamine are not that hard to get, also there are many substances that increase BDNF, like beta-alanine which I already mentioned.

And lastly there is the effects of androgens and estradiol on serotonin and SERT. I haven't done enough research on this area but androgens seem to have the ability to upregulate SERT with TPH2 as well. Estradiol also seems to do something similar but research on it is contradicting. Bacopa also upregulates tryptophan hydroxilase so it makes sense to think that most stuff that increase SERT mRNA expression also causes an upregulation in TPH. I'm not sure about the causation but it's something like your brain tries to keep these two in balance and change in the level of each causes the other's level to change too.
In contrast Fenclonine induced serotonin depletion didn't cause a decrease in SERT mRNA expression.
cdraham
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Re: How does serotonin inhibit sexuality exactly?

Unread post by cdraham »

taarn wrote: Sat Apr 20, 2019 5:28 pm
Jaxx wrote:Any thoughts on Tianeptine? Ive read some contradictive stuff if it really decreases serotonin.
First I also found Tianeptine as interesting but I've also read contradicting stuff. But finally I thought I won't be tinkering with it. If I remember well it enhances SERT binding but can decrease SERT mRNA expression. It also does something like making dopamine receptors more sensitive.

I haven't found anything good to decrease central serotonin. Probably beta-alanine has such effect but I think it's very mild.
If you want to increase/enhance SERT your best bet is Evodiamine and Forskolin, as far as my knowledge goes. Bacopa is also an option but it has more serotonergic effects which I'm not sure are good.

Increasing BDNF can be useful too. (https://www.ncbi.nlm.nih.gov/pubmed/18474368)
Alazocine (SKF-10047) which is a sigma-1 agonist also has the ability to increase serotonin reuptake by SERT.

And there are the TPH inhibitors like Fenclonine and a few others. If you want to do some manipulation with serotonin receptors with the goal of reversing PSSD and getting out of the current bad homeostasis, I think a TPH inhibitor can be useful. The best would be to permanently enhance SERT function, we would need to trial this more. Forskolin and Evodiamine are not that hard to get, also there are many substances that increase BDNF, like beta-alanine which I already mentioned.

And lastly there is the effects of androgens and estradiol on serotonin and SERT. I haven't done enough research on this area but androgens seem to have the ability to upregulate SERT with TPH2 as well. Estradiol also seems to do something similar but research on it is contradicting. Bacopa also upregulates tryptophan hydroxilase so it makes sense to think that most stuff that increase SERT mRNA expression also causes an upregulation in TPH. I'm not sure about the causation but it's something like your brain tries to keep these two in balance and change in the level of each causes the other's level to change too.
In contrast Fenclonine induced serotonin depletion didn't cause a decrease in SERT mRNA expression.
Tianeptine lowered SERT in dorsal raphe nucleus but increase SERT in other brain regions - imo a good option, maybe with something that lowers serotonin and upregulates 5ht1a.
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Delfador
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Delfador »

Y'all still really think excess serotonine causes libido loss... while some of the horniest people I known were on mdma and 5ht agonists... pssd is NOT a state of excess serotonine. Get that idea out of your minds and you will start looking in the right direction
cdraham
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Re: How does serotonin inhibit sexuality exactly?

Unread post by cdraham »

Delfador wrote: Thu Nov 26, 2020 1:53 pm Y'all still really think excess serotonine causes libido loss... while some of the horniest people I known were on mdma and 5ht agonists... pssd is NOT a state of excess serotonine. Get that idea out of your minds and you will start looking in the right direction
I think those serotonergic issues vary from sufferer to sufferer. Yes mdma and 5ht agonist.. They wont chronically downregulate all other serotonin receptors permanently. In pssd, if postsynaptic 5ht1a is desensitized, 5ht2c, 5ht2a etc. All those serotonin receptors will get disrupted and partly cause our symptoms. Im not saying they are the only thing disrupted in pssd. I think why noone really got success or barely anyone is that they werent really able to fix the serotonin feedback loop. It requires lowering central serotonin, upregulating SERT, upregulating 5ht1a at the same time else the down stream receptors wont go back.
Tree
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Tree »

Delfador wrote: Thu Nov 26, 2020 1:53 pm Y'all still really think excess serotonine causes libido loss... while some of the horniest people I known were on mdma and 5ht agonists... pssd is NOT a state of excess serotonine. Get that idea out of your minds and you will start looking in the right direction
Our bodies don't clear serotonin effectively because sert has been impaired. As a result our serotonin receptors have been desensitized causing sexual and cognitive symptoms. Mdma would most likely make our symptoms worse because it would further desensitize serotonin receptors. You can test this hypothesis yourself but if you suffer from severe pssd I'd highly recommend against it. I found out the hard way getting serotonin syndrome from just eating ginger.
arahant
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Re: How does serotonin inhibit sexuality exactly?

Unread post by arahant »

Tree wrote: Thu Nov 26, 2020 8:14 pm
Delfador wrote: Thu Nov 26, 2020 1:53 pm Y'all still really think excess serotonine causes libido loss... while some of the horniest people I known were on mdma and 5ht agonists... pssd is NOT a state of excess serotonine. Get that idea out of your minds and you will start looking in the right direction
Our bodies don't clear serotonin effectively because sert has been impaired. As a result our serotonin receptors have been desensitized causing sexual and cognitive symptoms. Mdma would most likely make our symptoms worse because it would further desensitize serotonin receptors. You can test this hypothesis yourself but if you suffer from severe pssd I'd highly recommend against it. I found out the hard way getting serotonin syndrome from just eating ginger.
Serotonin syndrome is a life threatening situation, how did you resolve it? Did the doctors recognize it at the ER? Cyproheptadine?
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)
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Delfador
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Delfador »

The nerves on these ones... I'm telling him 5ht is not chronically elevated and in his defense he tells me 5ht2a and 5ht2c are downregulated in pssd sufferers... which not only is false, but totally irrelevant because 5ht2 up and downregulation has little to do with 5ht levels in the first place...

And no, you did not get serotonine syndrome from ginger because an agonist wont give you serotonine syndrome even with very elevated serotonine levels. You wont get serotonine syndrome even with 10× the normal synaptic serotonine concentrations... you need something like 50× or 100× for that, which you will only get with a reuptake inhibitor and a MAOi or similar enzymatic enhibition pathways.

Saying you got serotonine syndrome with an agonist is like saying you overdosed on lsd. Sorry buddy, it's not happening.

But you had high serotonine side effects, no doubt.
cdraham
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Re: How does serotonin inhibit sexuality exactly?

Unread post by cdraham »

Delfador wrote: Fri Nov 27, 2020 12:34 am The nerves on these ones... I'm telling him 5ht is not chronically elevated and in his defense he tells me 5ht2a and 5ht2c are downregulated in pssd sufferers... which not only is false, but totally irrelevant because 5ht2 up and downregulation has little to do with 5ht levels in the first place...

And no, you did not get serotonine syndrome from ginger because an agonist wont give you serotonine syndrome even with very elevated serotonine levels. You wont get serotonine syndrome even with 10× the normal synaptic serotonine concentrations... you need something like 50× or 100× for that, which you will only get with a reuptake inhibitor and a MAOi or similar enzymatic enhibition pathways.

Saying you got serotonine syndrome with an agonist is like saying you overdosed on lsd. Sorry buddy, it's not happening.

But you had high serotonine side effects, no doubt.
What do you think happened in pssd to serotonin and the serotonin receptors then?
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Delfador
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Delfador »

5ht2a and 5ht2a are upregulated. Those are the receptors that inhibit dopamine firing. Those receptors also don't even need an agonist to be activated. They have an intrinsic constitutive activity. And their high activity therefore does not reflect serotonine levels.

5ht2c, the worst of all, upregulates in response to stress and to glucocorticoid receptor agonists.

Other than that, some of us have high and some of us have low serotonine but serotonine level is definitely not what unites us in pssd.

Some of us even recovered after sjw usage. And some feel great while on it. There is no way sjw lowers serotonine levels. Whereas some tried fenclonine and felt like rubbish. And that is the most potent serotonine suppressor.

You know why? You need highish serotonine levels to have a high libido. No man in human history has had erectile dysfunction and asexuality from being generally content with his life (highish serotonine).
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