MDMA Sexual Dysfunction - PSSD link (Oxytocin?)

[taarn]

Recently I was just talking with my friend who had his first MDMA experience (1 tab / night with some alcohol).

He said that for about 3 days after that night, he got temporary sexual dysfunction. The symptoms were exactly like my main PSSD symptoms.
That means lack of sexual feeling and pleasure in genital area and muted orgasms, but no ED. Of course this was accompanied by the lack of libido. This also happened at 90-95% of my MDMA experiences, the longest 'temporary sexual dysfunction' took about a week. My PSSD symptoms are the same, except that it just doesn't want to go away and stuck in that state.

So what could have happened? I suspect it's a desensitization of postsynaptic 5-HT1A receptors, which causes blunted oxytocin, etc.. release which in the end results in complete lack of pleasure and muted orgasms. Oxytocin is very important for orgasm intensity and levels elevate through the buildup to orgasm.

Aside this I've read a paper (https://www.ncbi.nlm.nih.gov/pubmed/17233773) that Oxytocin release and postynaptic 5-HT1A activation is responsible for the latency of the onset of sexual (orgasmic) dysfunction that antidepressants cause. This may also be responsible for that some individuals experience even a libido increase when beginning to take SSRIs.

The question is why does sexual function return after MDMA use and what's different with antidepressants. All I know is that I got sexual dysfunction from Mirtazapine which causes indirectly more serotonin at 5-HT1A receptors, effectively causing desensitizaton. MDMA also bombards 5-HT1A (and also other) receptors with their ligand, so that makes sense it causes desensitization. Is it that certain antidepressants increase cortisol and glutamate levels unlike (or more like) MDMA?

Is 5-HT1A activation mediated Oxytocin release absolutely essential for proper sexual function, I mean for feeling pleasure during the buildup process and having a satisfying orgasm in the end? Very likely because it doesn't matter how much I augment my dopaminergic neurotransmission by itself I can't really achieve any improvements pleasure and orgasm-wise. If I take the correct combination of medications and have some luck I'm able to have some return of feeling and probably libido.
I can also achieve pleasureless erections to visual stimuli which also implies that my dopamiergic function works more or less.

For me this implies that without postynaptic 5-HT1A activation and likely Oxytocin release we can't have proper sexual function. So the next thing I will do is getting some Oxytocin and do some experimenting.

I don't say this is everyone's only problem. But those who doesn't have ED and real genital numbness but only have issues with lack of pleasure and muted orgasms (without further cognitive symptoms), very likely their main (even probably only) problem is the desensitization/downregulation of postsynaptic 5-HT1A receptors.

Please feel free to comment, @Mesolimbo is very welcomed.

[Meso]

HPA axis reactivity is extremely important for sex as well. Recently, I've been experimenting a little with things that raise cortisol and I can have more than 1 orgasm per day if I have sex multiple of times. On my previous 100% symptomatic relief regimen, I can have 1 orgasm per day despite having sex twice, and if I try really hard maybe I get a second one, but it's rare.

Oxytocin and beta-endorphin (phasic) are crucial for orgasms, but also glutamate. Your neurons have to be able to get excitable, after all, and glutamate/ca release are essential downstream steps.

SSRIs upregulate the GR and cause HPA blunting and lowering cortisol -> glutamate. MDMA doesn't do that and it's not a long-term drug that you need to keep in your system 24 hours for months or years unlike SSRIs.

Also, keep in mind that many people don't get PSSD from antidepressants, it's only us that are unlucky enough to get it, which means there is a genetic vulnerability affecting our 5HT1A receptor regulation.

If you have more questions, feel free to ask.

[taarn]

HPA axis reactivity is extremely important for sex as well. Recently, I've been experimenting a little with things that raise cortisol and I can have more than 1 orgasm per day if I have sex multiple of times. On my previous 100% symptomatic relief regimen, I can have 1 orgasm per day despite having sex twice, and if I try really hard maybe I get a second one, but it's rare.

What are you experimenting with? Licorice? I also read that even grapefruit juice is able to increase cortisol.

SSRIs upregulate the GR and cause HPA blunting and lowering cortisol -> glutamate. MDMA doesn't do that and it's not a long-term drug that you need to keep in your system 24 hours for months or years unlike SSRIs.

Also, keep in mind that many people don't get PSSD from antidepressants, it's only us that are unlucky enough to get it, which means there is a genetic vulnerability affecting our 5HT1A receptor regulation

Yes, sorry I wasn't clear enough. I meant those who got PSSD from only just a few pills. In those cases the HPA dysregulation and GR upregulation happened in just a fraction of time?

What I wanted to say is that MDMA causes the exact same symptoms, except that it goes away with time. The reason behind it sticks with ADs can be the HPA/GR issue. But what's the mediator between the exact similarities? I guess it's not HPA blunting and eventual cortisol and glutamate release, cause MDMA doesn't cause these. But rather something like Oxytocin that is released following postsynaptic 5-HT1A activation. Following this logic it makes sense to think that activation of those receptors and the release of different brain chemicals are necessary for sexual and orgasmic pleasure.

Also, keep in mind that many people don't get PSSD from antidepressants, it's only us that are unlucky enough to get it, which means there is a genetic vulnerability affecting our 5HT1A receptor regulation.

My friend is also the anxiety-hypersexual type, likely he's also somewhat predisposed to PSSD.

[Meso]

What are you experimenting with? Licorice? I also read that even grapefruit juice is able to increase cortisol.

Yes, but also with something else that I'll keep secret for the time until I'm certain it works.

Yes, sorry I wasn't clear enough. I meant those who got PSSD from only just a few pills. In those cases the HPA dysregulation and GR upregulation happened in just a fraction of time?

It happens through LTP and LTD disruption from a few pills if you already have high cortisol, since SSRIs would further increase cortisol initially.

What I wanted to say is that MDMA causes the exact same symptoms, except that it goes away with time. The reason behind it sticks with ADs can be the HPA/GR issue. But what's the mediator between the exact similarities?

Postsynaptic 5HT1A desensitization. MDMA is a potent serotonin releasing agent, and the empathogenic effect is mediated through powerful postsynaptic 5HT1A activation, resulting in desensitization and eventual loss of "MDMA magic" and PSSD-like symptomology.