5-HT2A And MALE Sexual Function Thread

Lokzo

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In this thread, I want help to explore how the 5-HT2A receptor is implicated in all aspects of male sexuality, including orgasm, arousal, ejaculation, hormone secretion etc.

I will probably set up another thread dedicated to 5-HT1a, 5-HT2c, 5-HT1B, 5-HT2B later...

Well, where shall we start? Which region of the brain?

Here's what I've found so far:
https://www.researchgate.net/public...sticular_Response_to_the_Presence_of_a_Female
 

managing

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Sounds like a great idea for a thread to me. Apparently nobody is up for it though . . .
 

lampofred

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I've heard 5HT-2A does increase testosterone but it is up-regulated by stress.
 

Terma

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If you're most concerned with libido in this thread, yes it's a little reductionist. I think a combination of histamine (histidine or receptor agonists/antagonists) and acetylcholine (higher dose alpha-GPC or receptor agonists/antagonists) modulation is likely to help sexual dysfunction. Choline would help explain why despite a massive onslaught of health problems and awful cold exposure I always maintained a working nervous system under normal libido. On top, the cholinergic system might help explain partly why estrogen fuels sexuality. 5-HT2a also contributes (also can help maintain testosterone even through stress) - I refer to the Selfhacked page. That seems like more than enough to synergize. It so happens cyproheptadine modulates (antagonizes) all of these. Then you must factor in oxytocin and vasopressin, also released by 5-HT receptors. It's not one thing.

Cholinergic facilitation of erection and ejaculation in spinal cord-transected rats. - PubMed - NCBI
Functional significance of muscarinic receptor expression within the proximal and distal rat vagina
https://sci-hub.tw/10.1016/j.mce.2003.10.040
Behavioural effects of histamine and its antagonists: a review. - PubMed - NCBI
 
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Lokzo

Lokzo

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If you're most concerned with libido in this thread, yes it's a little reductionist. I think a combination of histamine (histidine or receptor agonists/antagonists) and acetylcholine (higher dose alpha-GPC or receptor agonists/antagonists) modulation is likely to help sexual dysfunction. Choline would help explain why despite a massive onslaught of health problems and awful cold exposure I always maintained a working nervous system under normal libido. On top, the cholinergic system might help explain partly why estrogen fuels sexuality. 5-HT2a also contributes (also can help maintain testosterone even through stress) - I refer to the Selfhacked page. That seems like more than enough to synergize. It so happens cyproheptadine modulates (antagonizes) all of these. Then you must factor in oxytocin and vasopressin, also released by 5-HT receptors. It's not one thing.

Cholinergic facilitation of erection and ejaculation in spinal cord-transected rats. - PubMed - NCBI
Functional significance of muscarinic receptor expression within the proximal and distal rat vagina
https://sci-hub.tw/10.1016/j.mce.2003.10.040
Behavioural effects of histamine and its antagonists: a review. - PubMed - NCBI


I thank you for the information.

The Histamine receptors are definitely huge players in libido.

And since Yohimbine also improves acetylcholine release, that might help explain its potent libido enhancing properties.

Good point about Cyproheptadine. I feel like this drug has really really helped me. Thank you again @Hedgehog .

I feel like the more I use, the more of my original personality is re-emerging. It's like this was taken from me when I used KSM-66.

Cypro feels like a master re-set for me.
 

LeeLemonoil

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Do primarily PDE5-inh. like cialis affect the discussed receptors in some way too or is their effect really only explained by the mechanisms described (pde5/NO)?
 
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Lokzo

Lokzo

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Do primarily PDE5-inh. like cialis affect the discussed receptors in some way too or is their effect really only explained by the mechanisms described (pde5/NO)?

I found a study on Viagra, I'll post here:

Central action of sildenafil on arousal and reward pathways

In addition to its peripheral effect on the corpus cavernosum, phosphodiesterase 5 (PDE5) inhibitor sildenafil also exerts effects on the central nervous system to modulate arousal, according to the findings of a new study. A team of researchers from Athens, Greece, studied the effects of sildenafil administration on dopaminergic and serotonergic activity in the nucleus accumbens (NAcc) and the medial preoptic area (MPOA) of the brains of male rats during sexual arousal. Sildenafil was administered for either 2 days (to model acute administration) or 21 days (to simulate chronic treatment). 30min after the last injection, rats were exposed to females in oestrus during a noncontact erection session. Half of the males had previous experience of a noncontact sexual encounter and the other half did not. After the encounter, levels of dopamine, serotonin and their metabolites were measured in the two brain areas using high-performance liquid chromatography. Turnover of dopamine and serotonin were also calculated as markers of neurotransmission. In inexperienced males, acute and chronic sildenafil treatment increased both dopamine and serotonin turnover rates in the MPOA and in the NAcc. The same was true for acute treatment of experienced rats, but chronic treatment enhanced serotonin turnover only in the MPOA and dopamine turnover only in the NAcc. This discrepancy could be due to a greater stress effect in experienced male rats, as copulation was prevented. An effect of sildenafil on dopaminergic neurotransmission has been suggested in the past, but this is the first time that the MPOA has been implicated and that an effect on serotonergic activity has been demonstrated. The authors hypothesize that modification of the nitric oxide–cyclic guanosine monophosphate pathway, which is the target of action of PDE5 inhibitors, might be involved, as dopamine release in the MPOA before and during copulation is modulated by nitric oxide. The effect of sildenafil on motivation and arousal pathways could help explain its clinical utility in treating psychogenic erectile dysfunction.
 

Frankdee20

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Which receptor of 5ht is involved in Premature Ejaculation ? Some say high adrenaline and high histamine play a role, but I am unsure. It varies at times.
 

Mauritio

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In this thread, I want help to explore how the 5-HT2A receptor is implicated in all aspects of male sexuality, including orgasm, arousal, ejaculation, hormone secretion etc.

I will probably set up another thread dedicated to 5-HT1a, 5-HT2c, 5-HT1B, 5-HT2B later...

Well, where shall we start? Which region of the brain?

Here's what I've found so far:
https://www.researchgate.net/public...sticular_Response_to_the_Presence_of_a_Female
Please continue this thread . Very interesting approach.
 

Hans

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Which receptor of 5ht is involved in Premature Ejaculation ? Some say high adrenaline and high histamine play a role, but I am unsure. It varies at times.
5-HT1A appears to be involved in premature ejaculation. Reduced 5-HT1A function can cause you to struggle to orgasm. This is one way how SSRI drugs cause sexual function. Some SSRI drugs actually upregulate the 5-HT1A post-synaptic receptors, which could then cause premature ejaculation.
 

Frankdee20

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5-HT1A appears to be involved in premature ejaculation. Reduced 5-HT1A function can cause you to struggle to orgasm. This is one way how SSRI drugs cause sexual function. Some SSRI drugs actually upregulate the 5-HT1A post-synaptic receptors, which could then cause premature ejaculation.

Thanks, any thoughts on how to downregulate or reduce that receptor ?
 

Markus

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I don't know much about how to modulate specific serotonin receptors, but I have complete ejaculation control by controlling my state of arousal.
 

Markus

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I also feel that focusing more on your partner makes it almost effortless to control your ejaculation.
 

Jib

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I've said this before and said this again: Rexulti f***ed me up sexually (caused SEVERE premature ejaculation). Look at what it does:

"Brexpiprazole acts as a partial agonist of the serotonin 5-HT1A receptor and the dopamine D2 and D3 receptors...It is also an antagonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT7 receptors."

Pharmacological Studies on the Role of 5-HT 1 A Receptors in Male Sexual Behavior of Wildtype and Serotonin Transporter Knockout Rats - PubMed

"Brain serotonin (5-HT) neurotransmission plays an important role in male sexual behavior and it is well established that activating 5-HT1 A receptors in rats facilitate ejaculatory behavior."

I'm closing in one 1 year after stopping Rexulti. I haven't had sex in that time. I've also been practicing semen retention for over 2 months at this point. All very interesting stuff. That medication caused insane PE that I've never experienced before, to the point of not even being able to fully penetrate without ejaculating. From the moment of insertion, just my glans making contact with a vagina, I'd start to ejaculate. Awful, awful, awful, and never experienced that once in over 3 years of having sex on a regular basis with my ex girlfriend.

So I know for a fact that medication caused it, and it's a large part of why I stopped. I'm only hoping now that the changes were not permanent. You think you're in control of your mind and body until you experience something that totally takes you over and screws with your neurotransmitters and other chemicals/hormones.

Two things: ejaculation fantasy, and psychological control. It may be as simple as @Markus put it. Controlling your state of arousal. This is much easier said than done for people with severe PE. However, it gives hope.

In my experience, I think years of watching porn with a heavy focus on ejaculation ('cumshots' etc., girls making guys ejaculate in any number of ways), really screwed with me. However, the medication made any issues I had much, much worse. Many times I was able to have unprotected sex and maintain some control, even though I couldn't go as vigorously as I wanted without ejaculating. It was never at the level it was after medication: not even being able to penetrate at all without ejaculation. It was truly a nightmare and honestly it has made me afraid to even try having sex again at all for over a year since quitting.

I believe in the power of the mind. 100%. If you imagine ejaculating, and it excites you, there you go. You don't even need to have an erection to imagine this, and familiarize yourself with the sensation of the urge to ejaculate. The "ejaculation fantasy." It's basically a fetish. It was for me, anyway, and I noticed I'd always skip to the ejaculation points in a video, or simply look at GIFs looping ejaculation, as a result of a girl doing this or that or ejaculating during intercourse, etc.

In my years practicing "Faster EFT," which is heavily based on NLP, I learned a lot about the mind. It's going to sound crazy but I've tried using this technique while masturbating -- and as I mentioned, I'm practicing retention, and have not ejaculated in over two months. So masturbation for me always means self-stimulation without ejaculation. Still, I frequently have to pause if I get too excited.

Utilizing Faster EFT while masturbating I can maintain a lot more stimulation without the urge to ejaculate. Part of this is simply distracting yourself. That is not my goal. My goal is to go more fully into feeling everything and simply maintaining a calm state of arousal. Erection without the pressing urge to ejaculate.

I believe it's possible. I haven't tested with a partner but I've made tremendous progress on my own. Keeping in mind it's a marathon, not a race, just like building muscle. With PE we're talking about something either learned or even genetically ingrained that may take a lot of time and practice, over and over, to really gain control over. Never lose hope that it's possible.

But undoubtedly that medication (which is basically the successor to Abilify) really messed with me a LOT. There is absolutely a lot going on there with these receptors. And they can affect you in ways you'd never imagine. I was on Zyprexa for years as well and it zombified me, nothing I could have done about it. These kinds of drugs are not to be trifled with at all.
 

Frankdee20

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Jib - Damn bro, I’m sorry.... Things were bad for me after stopping Effexor back in 2008.... That’s what I think happened to me..... Things are better now, I have times when I last quite a while, and sometimes it’s just meh.... it gets better though, good luck... In your case, that’s definitely the medicine... what exactly do you think it did ?
 

Frankdee20

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Happy to say I will never take another psychiatric drug again, thank god for DR Peter Breggin and his website- Antidepressant Facts
 
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