Wellbutrin and 5HTA1

This is for hypothesis and even educated speculation.
PsychoGenesis
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Re: Wellbutrin and 5HTA1

Unread post by PsychoGenesis »

sovietxrobot wrote: Mon Nov 02, 2020 12:52 pm
PSSD_Throwaway28 wrote: Tue May 05, 2020 5:44 pm Hi guys,

Browsing the forums, it seems that the most popular theory regarding PSSD is that, in certain cases, use of SNRI's/SSRI's causes desensitization of the 5HTA1 receptors that persists even after the drug is discontinued. However, I'm having a little bit of trouble squaring this hypothesis with the fact that: (1) Wellbutrin typically resolves the sexual side effects of SSRI's that occur while people are taking them and (2) Wellbutrin seems to be the most promising drug in terms of improving the condition of people with PSSD - either temporarily or permanently.

The reason I have trouble squaring these two things is that Wellbutrin has also been shown to cause desensitization of the 5HTA1 receptor early on. In fact, this is part of the reason why it is sometimes recommended as an adjunct therapy to increase the effectiveness of SSRI's. Given this, if sexual side-effects were caused by 5HTA1 desensitization, wouldn't Wellbutrin tend to make things worse?

Am I missing something here?
someone else made this claim and I couldn't find any good evidence that Wellbutrin effects 5HT1A. its a dopamine reuptake inhibitor, I dont see how it would interact with 5HT1A. I am not sold on the 5HT1A desensitization theory either.
i think it was MrStairCase that posted before, it may help to search for bupropion instead of wellbutrin

https://pubmed.ncbi.nlm.nih.gov/18708076/

it seems to increase 5ht firing like a machine gun

arahant wrote: Mon Nov 02, 2020 11:05 pm
sovietxrobot wrote: Mon Nov 02, 2020 12:52 pm
PSSD_Throwaway28 wrote: Tue May 05, 2020 5:44 pm Hi guys,

Browsing the forums, it seems that the most popular theory regarding PSSD is that, in certain cases, use of SNRI's/SSRI's causes desensitization of the 5HTA1 receptors that persists even after the drug is discontinued. However, I'm having a little bit of trouble squaring this hypothesis with the fact that: (1) Wellbutrin typically resolves the sexual side effects of SSRI's that occur while people are taking them and (2) Wellbutrin seems to be the most promising drug in terms of improving the condition of people with PSSD - either temporarily or permanently.

The reason I have trouble squaring these two things is that Wellbutrin has also been shown to cause desensitization of the 5HTA1 receptor early on. In fact, this is part of the reason why it is sometimes recommended as an adjunct therapy to increase the effectiveness of SSRI's. Given this, if sexual side-effects were caused by 5HTA1 desensitization, wouldn't Wellbutrin tend to make things worse?

Am I missing something here?
someone else made this claim and I couldn't find any good evidence that Wellbutrin effects 5HT1A. its a dopamine reuptake inhibitor, I dont see how it would interact with 5HT1A. I am not sold on the 5HT1A desensitization theory either.
An amphetamine substituted (bupropion) being put alongside SSRIs as desensitization agents?
It's kinda weird that some theories have become the number one agent of psychological terror among sufferers. :o This one has become so strong that these days one poster on Reddit was completely hopeless because after his "internet self-research", he realized that cigarettes cause desensitization of these receptors, according to some rat studies, so that's why he was feeling shit... But he couldn't understand that the study was to evaluate tobacco addiction, cravings due to this hypothetical desensitization...The layman cannot understand the hierarchy in biomedical research...they don't imagine that the majority mechanisms in vitro are not confirmed in animals and the same happens from rats to human beings...from thousands of drug candidates, sometimes zero passes the test of the same action in humans.
are you still on buspar same dose and all?


btw, nicotine upregulates SERT
arahant
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Re: Wellbutrin and 5HTA1

Unread post by arahant »

PsychoGenesis wrote: Mon Mar 08, 2021 5:15 pm are you still on buspar same dose and all?
@PsychoGenesis
aa
Yes since February 2019, but I dropped from 60 mg (too much dizziness and overeating) to 30 mg (Just ok, no wow!).

Maybe, I go back for 45 mg which was the dosage where I got the best response so far.
btw, nicotine upregulates SERT
Can you share the study?
I looked into nicotine in the past but it seemed too messy, like more risks than benefits, even using nicotine gums.
I read somewhere that nicotine wd can be a nightmare.
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)
PsychoGenesis
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Re: Wellbutrin and 5HTA1

Unread post by PsychoGenesis »

arahant wrote: Mon Mar 08, 2021 10:52 pm
PsychoGenesis wrote: Mon Mar 08, 2021 5:15 pm are you still on buspar same dose and all?
@PsychoGenesis
aa
Yes since February 2019, but I dropped from 60 mg (too much dizziness and overeating) to 30 mg (Just ok, no wow!).

Maybe, I go back for 45 mg which was the dosage where I got the best response so far.
btw, nicotine upregulates SERT
Can you share the study?
I looked into nicotine in the past but it seemed too messy, like more risks than benefits, even using nicotine gums.
I read somewhere that nicotine wd can be a nightmare.
https://pubmed.ncbi.nlm.nih.gov/14515338/

it was Meso who first pointed it out


i don't use nor recommend corrupted tobacco only organic
finities infinities
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Re: Wellbutrin and 5HTA1

Unread post by finities infinities »

I think I know why NRIs can cause PSSD, and so is the case with mianserin and clomipramine.
It is about alpha2 receptors on serotonergic neurons. Administration of NRIs causes desensitization of these receptors and inhibition of serotonin release.
I think it doesn't even have to be a 5ht1a desensitization. Because the alpha2 adrenergic receptor seems to perform very similar functions, acting as serotonin autoreceptors.
II think than mianserin is the most dangerous ( I have PSSD after mianserin) because is 5ht2 inverse agonist+ NRI aand alpha2 antagonist but paradoxical downregulate this receptor. 5ht2+alpha2 and 5ht7 redirect serotonin release to 5ht1a receptors which are very strong indirect activation and fast desensitize. 5ht2a antagonist compensatory downregulate mglur2 and cb1 which are common heteromers with 5ht2a. Despite 5ht2a downregulation, mGlur2 downregulation, CB1 downregulation and sensitize stress system (5ht2 receptors release CRH, 5ht2 antagonism can restore stress responses by re-sensitizing the CRH system). This all leads to an hypersensitivity of 5ht2 receptors.)
Let's add a strong alpha2 + 5ht1a desensitization and a recipe for severe PSSD is ready.
flexstar13
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Re: Wellbutrin and 5HTA1

Unread post by flexstar13 »

arahant wrote: Sun Nov 01, 2020 3:13 pm
clong4324 wrote: Sun Nov 01, 2020 11:14 am tried zoloft which reinstated all sexual normalcy 100% for 2.5 years. Stopped zoloft w/ 2 week taper, crashed into debilitating withdrawal (inhuman depression) which would not let up after 6 weeks.
Wait, are you claiming Zoloft gave your normal sex life for 2.5 years?
That's impressive.
I am pretty much at the end after trying all supplements and hcg to raise my testo, without any benefit. Next step is Wellbutrin and than last resort ssri. So it seems to have worked for you… I am damn scared but I cannot go on like this…
ihatelexapro444
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Re: Wellbutrin and 5HTA1

Unread post by ihatelexapro444 »

I'm thinking of trying zoloft as well, just to reclaim my life since escitalopram induced PSSD, but I slept in bed all day on SSRIs, so I'd have to combine it with amphetamine for ADHD.
dosp35
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Re: Wellbutrin and 5HTA1

Unread post by dosp35 »

Wellbutrin did nothing to my PSSD. What really works for me, for low libido, is Vyvanse 70mg. It really increases my libido, but not erections quality. For erections, I use yohimbine and tadalafil with great results. These 3 medicines combo is perfect for my PSSD (Vyvanse 70mg, Yohimbine (16.2mg divided 3 times) and tadalafil (5mg).
Wellbutrin XL 300mg
Remeron 45mg
Rexulti 2mg
Vyvanse 70mg
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