Everything we knew about PSSD is wrong. Check out why.

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finities infinities
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by finities infinities »

Autoreceptors desensitization theory:
5ht1a desensitization and alpha2 adrenergic on serotonin neurons desensitization.
THC PAWS like symptoms from SSRIs and antipsychotic theory:
Cb1 desensitization ( and automatically NMDA+5ht2a hyperactivity and ,,flame" of anterior cingulate cortex. ( excess empathy, existential terror, depersonalization)
5ht2a/Mglur2 heteromer destabilization and symptoms like above ( cortical hyperexcitability)
DNA methylation ( epigenetic changes)---->. dopamine receptor downregulation, BDNF, and GAD67 loss.
Think that this all above theories are true.
Inositol activate D2 and 5ht2 receptors, this last are extreme dysphoric existential terror. D2 is totally opposite to 5ht2 receptors.
I think PSSD is sort of like an ongoing psychedelic trip that causes an altered state of perception, very dysphoric. After all, psychedelic trips are trumatic stressors and experiencing near-death states, existential crises.
I have noticed that serotonin inhibits sexual behavior by inducing a "dysphoric, stress state of mind" - it greatly stimulates the "terror" centers in the brain - insula, anterior cingulate cortex.
It is enough to go to reddit and read that under the influence of psychedelics, many people feel disgusted with sexuality, have thoughts about morality - about animals eating animals, experience an existential crisis, often suicidal with a sense of loss of meaning.
Yep, it's all serotonin.
Escitalopram, like many SSRIs, has additional mechanisms that oppose its serotonergic effects.( I believe it, maybe is NMDA antagonist and Ecb enhancer?) I saw that escitalopram is 5ht3 antagonist and upregulate this receptor ( which is also pro-anxiety pro-dysphoric).
The discriminatory stimulus of acute escitalopram is mimicked by a combination of a cb1 + 5htp agonist. CB1 and 5ht2a are in contrast, the cannabinoid inhibits the dysphoric effects of serotonin. CB1 greatly enhances sexual arousal and serotonin inhibits it by inducing existential terror. So acute escitalopram has a neutral effect on libido, followed by desensitization of 5ht1a and CB1. (and probably epigenetic changes). So the 5ht1a antagonist + CB1 antagonist could have reversed it partially or completely.
Why do I know the 5ht1a theory is true?
I found propranolol in my home (it has poor 5ht1a and 5ht1b blocking properties) and took it in a mega dose. It exacerbated the condition a lot, and when I took the propranolol + 5htp combinations then I was in the hell of existential terror. It was a nightmare, so it worsened the symptoms and there was a serotonergic hallucination.
When this combination stopped working I had a slight nocturnal erection and slighty ,,sexy vibe" rebound, apart from the strong adrenergic rebound (selegiline-style).
Ergogenic health - I think this is a battle between receptors, cypro has a lower affinity for 5ht1a than 2a, so maybe the blockade from the 5ht1a receptor is released first and you feel the "sexy vibe" and then 5ht2a rebound that inhibits sexuality and "animality instinct" "and your ego.
Maximus
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by Maximus »

I was taking lexapro 10 mg and trittico 75mg for 5 months and I had very decreased libido, reduced sensation and it was extremelly hard to orgasm. For an unrelated reason I decided to discontinue the drugs and the gp recommended to skip a dose every other day for 2 weeks and then stop alltogether, which in hindsight is a terrible way to taper off. The last pill I took was about 2 weeks ago and I've recovered from the afforementioned symptoms but I've developed ED since. I'm kinda stressing over this, does anyone have an tips or tricks? If I knew preemptively about the long term potential side effects I'd never take an ssri. fml
ihatelexapro444
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by ihatelexapro444 »

What are some current options for treating this?
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guacamo
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by guacamo »

I do not know right now, i test various ideas, but going through each takes time. I do have vague idea what might happen in a person with PSSD, but i do not know which combination of substances might be helpful. Patiency is all we need.
tonyareias
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by tonyareias »

Maybe the root / key is in Acetylcholinesterase.

Facts:
- Acetylcholine presence and transmission are essencial for sex;
- SSRIs are acetylcholinesterase inhibitors then more acetylcholine are available
- Yes SSRIs give bad sex effects but are all? about the boost of serotonin presence
- When you remove SSRI maybe some bodies don’t recover natural acetylcholinesterase inhibition and acetylcholine just destroyed quickly
- When you do an SSRI reinstatement with low / micro dosing you get the balance of not so must serotonin and gain acetylcholinesterase inhibition allowing more acetylcholine presence

Just like PDE5 inhibitors (allow cGMP presence), acetylcholinesterase inhibitor allow the presence of acetylcholine.

Remember: The sex start on the head and acetylcholine is the key for body reaction and sensations.
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guacamo
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by guacamo »

If that would be true then there should be more reports of taking acetylcholinesterase inhibitors helping people, which does not happen.
tonyareias
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by tonyareias »

Inhibition of acetyl- cholinesterase (AChE) is another target for the treatment of ED as it regulates the levels of ACh, which trigger NO-dependent.
https://www.tandfonline.com/doi/pdf/10. ... 17.1340966

https://www.sciencedirect.com/science/a ... 4717413425

https://www.nature.com/articles/3901169

There’s some studies that suggests “Bee Honey” as natural AChE inhibitor.
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guacamo
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by guacamo »

I know that acetylcholine is involved in sexuality, but i do not think that it does play any role in PSSD. It may help, but it's like having flu and taking amphetamine, yes you will feel better, but it is not because amphetamine cures flu.
prop
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by prop »

guacamo wrote: Tue Jun 29, 2021 6:07 am 2. Increasing dopamine does not improve symptoms.
You mean, not immediately. I know of 3 cases of people curing themselves with dopamine releasers. In every case, the cure was not immediate, and in 1 of those cases actually acutely worsened PSSD symptoms.

https://reddit.com/r/pssdhealing/commen ... s_stories/
Archive of PSSD recovery stories: https://pssd.netlify.app/
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guacamo
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Re: Everything we knew about PSSD is wrong. Check out why.

Unread post by guacamo »

I was not on the forum for quite a long time, but I am still passively reading, this thread might be somewhat outdated. I was pretty much inexperienced in the phenomena of PSSD back then. Since then i expanded my knowledge tremendously. It is quite funny that i made pretty good shoots back then while not having that good of a perspective in terms of knowledge. I am on a point where I can consistently reduce the symptoms to about 25% or less, of what it would otherwise be, the problem with this protocol is that I would be unable to translate it for the benefit of the community, because it is so relative, though I still believe I am closer and closer to the answer with every day.

I may be able to write a thread to shed the light of the etiology in particular, in the next few weeks (or earlier, depending on how fast I will gather necessary information), with much more deailed and matured form than what my previous threads were. In the end what problems I face is that the management could lead to crash if gone wrong, and it relates not only to the wrong approach by the person who does the protocol, but also to his personal biological predisposition, therefore it is impossible to write such protocol in general form to benefit everyone equally.

I also understand the desperate position everyone who suffer from this disease is in, so I do not want to give you promise that i will cure you in the near future,, so please do not bring your hype up to that level, but I may be able to explain to you how mechanism of action of things like SSRI, 5-HT1A, isotretinoin, inositol, st john wort, methyl donors like b12, methylfolate, inositol, etc, could be, in far more detailed version than before, approach that i have never seen be made in detail by anyone in the PSSD community or in related scientific work. That would obviously led people to make conclusions and jump to various treatments by themselves, and I would like to give such people best possible chance to make informed decisions.

Still need to research certain things, and learning about particular topics that do not relate directly to each other is no easy task. The biggest problem is to digest content from somewhat unrelated topics in the understading of human physiology in the general molecular biology related papers, but in this particular disease, very relevant, but since there is not much research going on about PSSD, I have to try to make conclusion from the afromentioned papers, because of this, there are some hits, but also lots of misses. For what i know right now PSSD is definitely manageable to satisfactory level and with knowledge i possess, I think it is curable (though i have ideas how, I am unable to give you particular protocol as of now) and PSSD is not related in my opinion to the cellular damage in any way, instead it is shift in cellular functioning, that would have to be switched back, to regain prePSSD health.
The thread I said I would like to write in the next few weeks will contain information about etiology, supplements, why some were cured and other were not with the same thing (with my educated guess), why some were having terrible crash with the same treatment other were cured by. This thread will most likely not containt protocol that would cure people in any form, though little ideas of such might slip up here and here in a limited way. I will try my best to write such thread as early as possible, but I still prefer to rather to post the best possible content I can, later on, than compromise on quality and rush on things. I also do other works, so i can not go and nurture the topic with all the free time i have. It will be unlike any other thread i wrote before, so please do not judge me based on these.

#edit
You could also let me know if you would like for this topic to be as broad as possible, or be like a summary of the most important parts. The broad version, while obviously trimmed to the most relevant information, might still be several pages long and I am not sure if many people in this forum would be able to digest that much of a content, without any previous learning on the matter. Perhaps i may compromise on things and try to write somewhat both or take the best of both and form it into singularity, don't know yet, still would've appreciated your feedback.
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