Attempting to cure/reverse my own PSSD

[AnhedonicApe]

Disappointing you didn’t get the results you wanted but you should be proud of how far you made it. You have gotten further than any other PSSD member in understanding this shit. At least you know now that your body is capable of being 100% symptom free. Where do you go from here? Would cycling this regime be beneficial or would you hop back on the symptomatic relief?

The results I wanted were not sustainable due to tolerance. Next: I want to know why those receptors are downregulated in the first place. DNA methylation could be the answer, but I think it's the lazy answer. I mean, we could blame virtually everything on DNA methylation and be done with it, but this will get us no where.

I think it's time to research how sex hormones regulate the postsynaptic 5HT1A receptors.

Don't u think we should focus on how we could demethylate our genes instead of fighting our own altered homeostasis? I think thats a battle we will loose.

[magnilo]

as a sleep aid, trazodone is glorious. its pharmacodynamic profile also does not overlap with vortioxetine, except with added ht1a agoninsm. ive never tried them together (never had sleep problems on vortio), but im a fan of both. although vortioxetine lowers my penile sensitivity which is a minus. which dose were you on? ive seen a paper (ive posted it somewhere) which mentions lower doses ~5mg give noticeable improvement in ASEX ratings (i think it was ASEX)

[ferdydurke]

Hi, Mr. Mesolimbo. Will you please take a look at my thread (http://www.pssdforum.com/viewtopic.php?f=41&t=2972) and help me with some advice?

[succubus76]

Presynaptic 5HT1A are autoreceptors, so abnormal sensitivity of them would mean postsynaptic 5HT1A receptors aren't getting activated and are muted/inhibited.

Presynaptic autoreceptor supersensitivity could be a defend mechanism of the brain due to chronic elevated serotonin? The brain try to get rip off the excess of serotonin by upregulating the autoreceptor, and for whatever reason they keep upregulated after the antidepressant is whitdrawal. Resulting in some of our symptoms

You said your pssd was presynaptic supersensitivity in nature

[Meso]

Presynaptic autoreceptor supersensitivity could be a defend mechanism of the brain due to chronic elevated serotonin? The brain try to get rip off the excess of serotonin by upregulating the autoreceptor, and for whatever reason they keep upregulated after the antidepressant is whitdrawal. Resulting in some of our symptoms

You said your pssd was presynaptic supersensitivity in nature

Presynaptic 5HT1A receptors actually downregulate in response to excess serotonin. That's how SSRIs work, as they bombard your autoreceptors until downregulation occurs (~4-6 weeks). After that, they activate postsynaptic 5HT1A receptors in a tonic manner, leading to antidepressant effect. Although the antidepressant effect is more complex than that since they also upregulate GR and blunt your HPA axis and trigger hippocampal neurogenesis, but you get the idea.

My recent research has also revealed that mu opioid and glutamate signalling are severely disrupted in PSSD, causing anhedonia and blunted affect. Although raising oxytocin via postsynaptic 5HT1A activation would restore some mu opioid receptor sensitivity, it doesn't solve the underlying issues or the root cause of why mu/glutamate signalling are this disrupted.

Since phasic activation of mu receptors in the mPOA increases libido (don't confuse it with tonic activation which decreases libido and lowers testosterone), then a healthy hedonistic response is needed for libido, orgasmic intensity, and the emotional response.

PSSD pathology is very complex, but I think relief is very possible.

[succubus76]

Im not close to your knowledge, forgive me if I commit a mistake. As always, thanks for sharing your findings c':

I think the main cause involves some unknown hpa axis disrupted feedback, since oxytocin is sintetized in the hypothalamus and then stored in the pituitary.
And meaby theres some estrogenic factor too, since strogen modulates oxytocin too.

Also oxytocin reduces cortisol, I believe some members here have high cortisol

Low levels of oxytocin in the brain are associated with several mental health conditions such as tinnitus

If you hpa axis is fuked, then it makes sense that you oxytocin production too, since it's sintetized there

I found this:

Estrogen has been found to increase the secretion of oxytocin and to increase the expression of its receptor, the oxytocin receptor, in the brain In women, a single dose of estradiol has been found to be sufficient to increase circulating oxytocin concentrations.

Female rats given oxytocin antagonists after giving birth do not exhibit typical maternal behavior.[60] By contrast, virgin female sheep show maternal behavior toward foreign lambs upon cerebrospinal fluid infusion of oxytocin, which they would not do otherwise

Impact on effects of alcohol and other drugs: According to several studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs (opiates, cocaine, alcohol), and reduces withdrawal symptoms)
This makes sense as why some members stop experiencing euphoria from drugs

Some researchers have argued oxytocin has a general enhancing effect on all social emotions, since intranasal administration of oxytocin also increases envy and Schadenfreude.
Interesting that here are suggesting that is involved in "bad emotions" such as envy and therefore anger too.

Estrogen has been shown to stimulate the release of oxytocin from the hypothalamus and promote receptor binding in the amygdala

It has also been shown that testosterone directly suppresses oxytocin in mice


https://en.m.wikipedia.org/wiki/Oxytocin

Research shows that Lactobacillus reuteri significantly increases oxytocin levels in the brain through the vagus nerve (26-29).

Lactobacillus reuteri is usually found in the human gut. However, not all humans have it, and some people simply have very low levels of it.

One study found that the absence of lactobacillus reuteri causes social deficits in animals. By adding it back in to the guts of the animals, the researchers were able to reverse some of their behavioural deficits, which were similar to symptoms of social anxiety and autism in humans

This is a good article and it worth a read:

https://www.optimallivingdynamics.com/b ... -the-brain

Is there a blood test that allows you to measure oxytocin? There's a way to prove we have low oxytocin production or something like that?

[kpavel]

So it seems estrogen receptor type alpha positively modulates both oxytocin, and kisspeptin and orexin.

By the way Cipro also wrote about good microflora recently, And it's definitely vagus nerve influence on anxiety. I have some knowledge on this. For example Polyvagal theory of psychiatric disease by Porges. He describes 3 primitive reactions via branches of vagus nerve - freeze, fight or fight. Or communicate (which is not anxiety).
http://area-1255.forumotion.com/t194-it ... s-articles

[Meso]

Blood oxytocin test is believed to reflect its level in the brain. However, measurement methods give different readings and none of the methods correlated to each other.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722864/

It's useless to test oxytocin through a saliva test. Oxytocin's characteristics don't allow it to pass easily from the blood into the saliva. A salivary test won't correlated with blood values, let alone with values in the brain.

This is an excerpt from my article on estrogen:

ER-α activation induces oxytocin receptor expression both in the brain and periphery [22], whereas ER-β activation induces hypothalamic oxytocin release [23]. Oxytocin neurons of the paraventricular and supraoptic nuclei express GPR30, so activation of GPR30 causes oxytocin release [24], which might mediate estradiol's rapid antidepressant effect.

ER-α activation upregulates 5HT1A receptors.[Estrogen article]

It's just a baseless hypothesis, but I think we might have a reduced estrogen signalling or a silenced subpopulation of receptors. The reduced postsynaptic 5HT1A activity I experience + the beneficial effects of serotonin releaser or postsynaptic activation could be caused by reduced estrogen signalling.

Regarding the microbiome, I had seriously considered getting a fecal transplant from a healthy donor at one point before learning that the technology wasn't available where I live.

[enriqueiglesias]

That is interesting, note how things which are said to promote (male) libido, like Tribulus, Wild Yam and Muira Puama (I can say the latter is at least better than Maca), or just to be good supplements in general (Licorice, Gotu Kola, Gingko), are said to have bindings to the estrogen receptor:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397262/

[PsychoGenesis]

if serves as anecdote, when i injected nandrolone and dropped test there was a estrogen buildup(assuming 17b-hsd induction from test + E1 increase from nandro + E2 from test) my libido shot to hardcore levels, both sensitivity/quality/frequency of erections came back along with insane libido

from nothing in the past 2-3 months to 3-4x a day rock hard for half a week before homeostasis caught up