desensitization 5ht1a

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JustOnlyHope
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desensitization 5ht1a

Unread post by JustOnlyHope »

Hey guys, quick question.

Everybody says about desensitization 5ht1a which might cause PSSD. So I don’t get it one thing, why Buspar or vortioxetine could be(not saying it is for sure) good as agonist 5ht1a if it lead to desensitization also?

I have no idea how it works that why I am asking, just curious...
finities infinities
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Re: desensitization 5ht1a

Unread post by finities infinities »

It doesn't seem to get any better. I'd say buspirone is worse than some SRIs like clomipramine. My libido was low despite taking clomipramine until I joined buspridone which deepened my PSSD and led me to extreme morality disgust, empathetic state. Vortioxetine is SSRI+5ht1a agonist, this look very dangerous.
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Meso
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Re: desensitization 5ht1a

Unread post by Meso »

JustOnlyHope wrote: Sat Feb 06, 2021 11:08 am Hey guys, quick question.

Everybody says about desensitization 5ht1a which might cause PSSD. So I don’t get it one thing, why Buspar or vortioxetine could be(not saying it is for sure) good as agonist 5ht1a if it lead to desensitization also?

I have no idea how it works that why I am asking, just curious...
Buspirone isn't always good for sexual function. There are some people who got worse on Buspirone. It also has many other mechanisms of action to take into consideration, such as alpha-2 antagonism from its metabolite. Alpha-2 antagonism is pro-sexual as seen with Yohimbine. Its postsynaptic 5HT1A partial agonism (with low intrinsic activity) means it might lower 5HT1A-mediated prolactin and beta-endorphin release, which is another pro-sexual mechanism for a particular set of people but can also trigger anhedonia.

My point is, if you want to test a hypothesis in general, you will need a highly selective ligand so other mechanisms of action are out of the picture.
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JustOnlyHope
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Re: desensitization 5ht1a

Unread post by JustOnlyHope »

Meso wrote: Sat Feb 06, 2021 2:00 pm
JustOnlyHope wrote: Sat Feb 06, 2021 11:08 am Hey guys, quick question.

Everybody says about desensitization 5ht1a which might cause PSSD. So I don’t get it one thing, why Buspar or vortioxetine could be(not saying it is for sure) good as agonist 5ht1a if it lead to desensitization also?

I have no idea how it works that why I am asking, just curious...
Buspirone isn't always good for sexual function. There are some people who got worse on Buspirone. It also has many other mechanisms of action to take into consideration, such as alpha-2 antagonism from its metabolite. Alpha-2 antagonism is pro-sexual as seen with Yohimbine. Its postsynaptic 5HT1A partial agonism (with low intrinsic activity) means it might lower 5HT1A-mediated prolactin and beta-endorphin release, which is another pro-sexual mechanism for a particular set of people but can also trigger anhedonia.

My point is, if you want to test a hypothesis in general, you will need a highly selective ligand so other mechanisms of action are out of the picture.

Thanks a lot for your reply.

So quick story. I got PSSD from bupropion + Trazodone CR.

The funny thing is, I took Buspirone to fix my pssd and I got worse. I didn’t feel my genital, couldn’t reach an orgasm. Then I told to my self fuck it, nothing to lose so I took sertraline 25 mg and Trazodone CR 150 mg for 3 weeks and I recovered somehow. Now I can have an orgasm without any problem and feel me genitals almost normal(maybe totally normal the problem is I can’t remember how was it 6 months ago).

My problem now:
- Very weak pleasure during an orgasm
- can only get erection 20-30% without stimulation, with stimulation 80-90%
- I don’t think about sex at all just like this
- when I cum it was always big shot now it’s floating from penis, but the semen is normal
- I used to sweat a lot, now while working at the gym I almost don’t sweat
- I used to take a shit a lot now I have constipation
- I don’t feel the buzz from alcohol and have derealization

I quit it because I was worried to lost results.

My psychiatrist told me it’s good idea to take Vortioxetine but just only 5 mg.

What do you think? I know you can’t predict but maybe any suggest?

I really appreciate your help.
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Meso
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Re: desensitization 5ht1a

Unread post by Meso »

JustOnlyHope wrote: Sat Feb 06, 2021 2:25 pm My psychiatrist told me it’s good idea to take Vortioxetine but just only 5 mg.
I crashed from Vortioxetine before. I don't think it's a good idea as it would downregulate 5HT1A receptors too much. Are you off of all drugs now?

You might be interested in raising SERT and increasing 5HT1A autoreceptors' sensitivity. Cannabigerol (CBG) is a 5HT1A antagonist. Berberine and Evodiamine upregulate SERT, but Berberine has 5-alpha reductase inhibitory effect. Aside from these, there are research chemicals that work the same but more selectively.

In my opinion, it was the Trazodone inducing your symptoms, not the Bupropion, since SRI reinstatement benefited you a little.
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JustOnlyHope
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Re: desensitization 5ht1a

Unread post by JustOnlyHope »

Meso wrote: Sat Feb 06, 2021 2:46 pm
JustOnlyHope wrote: Sat Feb 06, 2021 2:25 pm My psychiatrist told me it’s good idea to take Vortioxetine but just only 5 mg.
I crashed from Vortioxetine before. I don't think it's a good idea as it would downregulate 5HT1A receptors too much. Are you off of all drugs now?

You might be interested in raising SERT and increasing 5HT1A autoreceptors' sensitivity. Cannabigerol (CBG) is a 5HT1A antagonist. Berberine and Evodiamine upregulate SERT, but Berberine has 5-alpha reductase inhibitory effect. Aside from these, there are research chemicals that work the same but more selectively.

In my opinion, it was the Trazodone inducing your symptoms, not the Bupropion, since SRI reinstatement benefited you a little.

Uhhh... I’m getting crazy, doctor say something else, you say something else. Don’t know what to do. Shit, that’s a nightmare.

How did you recover from vortioxetine crash?
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Meso
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Re: desensitization 5ht1a

Unread post by Meso »

JustOnlyHope wrote: Sat Feb 06, 2021 2:59 pm How did you recover from vortioxetine crash?
After a couple of months it got better but I never recovered from it 100%.
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JustOnlyHope
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Re: desensitization 5ht1a

Unread post by JustOnlyHope »

So, what is your point now? What problems you have? How long, and what did give you pssd?
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Re: desensitization 5ht1a

Unread post by Sb919 »

deleted-(got my answer on another thread)
Last edited by Sb919 on Tue Feb 09, 2021 8:27 am, edited 1 time in total.
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Meso
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Re: desensitization 5ht1a

Unread post by Meso »

JustOnlyHope wrote: Sat Feb 06, 2021 3:31 pm So, what is your point now? What problems you have? How long, and what did give you pssd?
I got PSSD from Venlafaxine + Clomipramine. I no longer have problems except for anhedonia and blunted affect.

The anhedonia was tolerable before I took Vortioxetine. After I crashed, the anhedonia got significantly worse and hasn't improved much. That said, I recovered from all other symptoms within a couple of months of the crash.

There are at least 3 members here who also crashed on Vortioxetine and got anhedonia. You should search the forum for Vortioxetine experiences.
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