POIS Theory Master List

[Muon]

Men versus women on sexual brain function: Prominent differences during tactile genital stimulation, but not during orgasm

"The only prominent gender difference during orgasm was male-biased activation of the periaqueductal gray matter."

Periaqueductal Gray

The neurobiology of central sensitization

We have similarly shown that decreased connectivity to antinociceptive brain regions, such as the periaqueductal gray (PAG - a critical locus of descending analgesic pathways), predicts responsiveness to milnacipran, a serotonin norepinephrine reuptake inhibitor. https://poiscenter.com/forums/index.php?topic=3312.0

It's worth noting that observations regarding POIS in / and / or MECFS go back (at least) some 25 years. Noted ME specialist Dr. Jay Goldstein in his 1996 Betrayal by the Brain:

"Several of my male patients have complained that they feel exhausted for several days after ejaculating. Although little is known about the central neurochemistry of orgasm, it appears that NE [norepinephrine] facilitates it, and that NE is depleted after ejaculation. If a male neurosomatic patient were deficient in NE prior to sexual activity, ejaculation could thereby worsen his symptoms" (Goldstein 1996: 63).

I took an epipen injection after a NE and it made things worse, my usual extreme headaches that comes with pois were mush worse and throbbing in my head, when the effect of the shot wore off i was dreadfully tired and fatigued. Sleeped for days

[Muon]

https://en.wikipedia.org/wiki/Norepinephrine
"Brain areas containing noradrenergic neurons"

[Muon]

Table 2: Potential biomarkers for the AIT efficacy, stratification and efficacy prediction.
Table 3: Biologicals used to support AIT.
Hot topics in allergen immunotherapy, 2023: Current status and future perspective

[Muon]

https://www.reddit.com/r/POIS/comments/18clapc/comment/kcc2rrg/

Guys this Tachycardia is killing me, can't concentrate, can't study ,have exams in a month.Have muscle pain,some cognitive symptoms,no brain fog though, can cope with them all except that disturbing tachycardia which gets better after ejaculation for about 6 to 8 hrs and then sets again despite plenty of rest.Fexo has little to no effect and also makes me dizzy.Only ibuprofen worked so far.

Hi All,

Demo and Daveman just received the public portion of Dr. Komisaruk's interim report from NORD. Here it is --

"A preliminary interpretation of our current data is that POIS symptoms are accompanied by a lowered heart rate and heart rate variability (HRV), and that vagal stimulation may produce a beneficial effect on POIS symptoms (increased heart rate and HRV) as a 're-bound' from the vagal stimulation. These are very preliminary findings and continued research with additional participants is underway, to assess the reliability of these findings."

Stef

Heard someone talking in this video that antihistamines can act negatively/positively depending on how the autonomic system behaves: https://www.youtube.com/watch?v=U0s26KdDDdU
His HR lowers after ejaculation.

[b_jim]

Wrong transsulfuration pathway.

[Muon]

(236) Flibanserin for Post-Orgasmic Illness Syndrome: A Case Report
https://academic.oup.com/jsm/article/20/Supplement_1/qdad060.222/7164839

Aside from raising brain levels of NE and DA:

ChatGPT 3.5

Q: What 5-HT receptor subtypes are present on human mast cells?

Human mast cells express various subtypes of serotonin (5-HT) receptors, and the activation of these receptors can influence mast cell function and mediator release. The specific subtypes of serotonin receptors found on mast cells include:

5-HT1 Receptors:
Subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F.
Function: Activation of 5-HT1 receptors on mast cells may inhibit the release of histamine and other inflammatory mediators.

5-HT2 Receptors:
Subtypes: 5-HT2A, 5-HT2B, and 5-HT2C.
Function: Activation of 5-HT2 receptors on mast cells can enhance the release of histamine and other proinflammatory mediators.

5-HT3 Receptors:
Subtypes: 5-HT3A and 5-HT3B.
Function: 5-HT3 receptors are ligand-gated ion channels. Activation of these receptors on mast cells may contribute to the release of histamine and other mediators, and their blockade is associated with antiemetic effects.

5-HT4 Receptors:
Subtypes: 5-HT4A and 5-HT4B.
Function: Activation of 5-HT4 receptors on mast cells may influence the release of various mediators, including histamine.

5-HT6 Receptors:
Subtype: 5-HT6.
Function: 5-HT6 receptors are primarily found in the central nervous system, and their role on mast cells is not as well-characterized.

5-HT7 Receptors:
Subtype: 5-HT7.
Function: Activation of 5-HT7 receptors on mast cells may influence the release of histamine and other inflammatory mediators.

The functional outcomes of serotonin receptor activation on mast cells can vary depending on the specific receptor subtype and the context of the immune response. For example, some receptor subtypes may promote the release of histamine and other proinflammatory mediators, while others may have inhibitory effects.

The modulation of serotonin receptors on mast cells is an active area of research, particularly in the context of allergic and inflammatory conditions. Understanding the specific roles of serotonin receptor subtypes on mast cells may contribute to the development of targeted therapies for conditions associated with mast cell activation, such as allergic diseases and mastocytosis.

Q: What is the potential effect of flibanserin with 5-HT receptors on mast cells?

The specific effects of flibanserin on mast cells would depend on several factors, including the distribution of serotonin receptor subtypes on mast cells, the concentration of flibanserin reaching peripheral tissues, and the overall pharmacological profile of the drug.

In general, the potential effects of flibanserin on mast cells could include:

5-HT1A Receptor Activation: Flibanserin acts as a 5-HT1A receptor agonist. Activation of 5-HT1A receptors on mast cells may have inhibitory effects, potentially reducing the release of histamine and other inflammatory mediators.

5-HT2A Receptor Antagonism: Flibanserin acts as a 5-HT2A receptor antagonist. Antagonism of 5-HT2A receptors may counteract some proinflammatory effects associated with serotonin receptor activation.

[hurray]

(236) Flibanserin for Post-Orgasmic Illness Syndrome: A Case Report
https://academic.oup.com/jsm/article/20/Supplement_1/qdad060.222/7164839

Very interesting, Muon. This would be top of my list of potential anti-POIS drugs to try because of its novel mechanism of action:

flibanserin has been described as a norepinephrine–dopamine disinhibitor (NDDI)

https://en.wikipedia.org/wiki/Flibanserin

Norepinephrine and dopamine disinhibitors (NDDIs) are a class of drugs which act at specific sites to disinhibit downstream norepinephrine and dopamine release in the brain

https://en.wikipedia.org/wiki/Norepinephrine%E2%80%93dopamine_disinhibitor

It's a drug designed to increase libido (for women!), you would expect it to have some kind of effect on male sexual function too. It worked for the one person in the case study, obviously that's no guarantee that it would work long-term or for a larger number of people, but it's still a starting point. I wonder if anyone else has attempted to copy the study?

[Muon]

Another case can be made for mast cell involvement. It seems to point in the direction of mast cells. Many treatments that are effective in POIS patients are able to block mast cell directly or indirectly. If true, then the mast cell needs to be played like a piano hitting the right tone(s) for each patient.

https://poiscenter.com/forums/index.php?topic=4375.msg47757#msg47757

[Muon]

Food for thought: How will low-dose IL-2 therapy affect POIS?
Targeting IL-2: an unexpected effect in treating immunological diseases

[Muon]

The case mentioned here is termed leukocytospermia, which may be indicative of ongoing inflammation due to ROS (e.g. prostatitis). Such a test may not necessarily reveal the root of POIS, but it may be a potentially useful biomarker. I wish some upcoming POIS study would address this issue.
https://poiscenter.com/forums/index.php?topic=3374.msg39428#msg39428

Lotti, F., & Maggi, M. (2013). Interleukin 8 and the male genital tract. Journal of reproductive immunology, 100(1), 54-65.

"thus suggesting that sIL-8 could be a marker not only of inflammation of the prostate, but also of other organs of the MGT, including the epididymis"

There are a couple of cases with epididymitis in POIS literature. I haven't seen ROS being measured in POIS studies.

[Muon]

I wonder whether injecting cromolyn sodium into the urethra would help some patients.

[Muon]

POIS inflammation depletes methyl groups. POIS mental symptoms are a result of depleted neurotransmitters, from depleted levels of SAMe. SAMe (S-Adenosyl-L-methionine) is required for the brain to synthesize the neurotransmitters norepinephrine, dopamine, and serotonin. SAMe is a universal methyl group donor. In addition to SAM-e, methyl B12, methylfolate (if tolerated), choline, and TMG (trimethylglycine) are all methyl donors, and should help to replace lost methyl groups from POIS, and thus help to fix POIS mental symptoms.

Evidence for S-Adenosyl-L-Methionine (SAM-e) for the Treatment of Major Depressive Disorder

AFAIK, the body utilises two main pathways for methylation:

1) B12 & folate dependent (you need adequate status of both nutrients for this pathway to work)

2) choline (if B12 or folate is low, then body will switch to choline pathway)

Ideally you have adequate status of all nutrients B12, folate, choline, for optimal functioning.

Those that respond to choline with an improvement with POIS symptoms may have a folate or B12 deficiency.

[Muon]

https://www.reddit.com/r/POIS/comments/1axrtdh/cure_or_not/

I was on risperidone (an atypical antipsychotic drug) for 4-5 months and when I ejaculated, I felt no pois symptoms.

Anyone from medicine back can help me to understand this.

I have discontinued this medicine.

https://en.wikipedia.org/wiki/Risperidone#Pharmacology

[Muon]

Multiplex cytokine assays can be used for research to investigate (dynamic) cytokine ratio’s.

[Muon]

https://www.reddit.com/r/POIS/comments/1b66yvv/pois_following_vaccines/

Has anyone noticed the onset of POIS or its severity increasing significantly following vaccination?

I can’t recall ever having these horrific hangover type effects from ejaculating prior to receiving two Moderna jabs during Covid.

My symptoms will sound familiar to all I am a sure - crushing fatigue and brain fog, swollen glands, insomnia, pale skin and an inability to concentrate.

I am going to try grounding and fasting to try and clear my body. I literally cannot ejaculate without wanting to spend the next 3 days in bed afterwards in a flu like state. Needless to say I now try to abstain 100%.

[Muon]

I should mention that when I abstain for at least a week and do an extended water fast I get the same exact effect that I do from methylene blue. I feel like there is a connection there but I don't know what it would be.

[Muon]

I couldn't find pseudoephederine, so decided to try a beta 2 agonist before orgasm. Beta 2 agonists are potent mast cell stabilizer. I took 10mg terbutaline oral 1 hour before orgasm. Unfortunately it didn't work and now I'm exhausted like never before with exteme anxiety brainfog and doom like feeling and also palpitations and joint pain.

I think pseudoephederine worked for some not because it works on mast cell but because it affects central nervous system. Terbutaline can't cross blood brain barrier so may be that's why it didn't work for me.

[Muon]

Methylene Blue is an inhibitor of sGC and NOS, this would increase GTP. Cialis inhibits PDE5 which would increase cGMP. What does this mean? Cialis is also a PDE11 inhibitor.

[Progecitor]

Methylene Blue is an inhibitor of sGC and NOS, this would increase GTP. Cialis inhibits PDE5 which would increase cGMP. What does this mean? Cialis is also a PDE11 inhibitor.

Alternatively tadalafil can also down-regulate Rho-kinase activity, which should reduce calcium ion intake, circumventing a possible Ca2+ overload, similarly to PMCA activation by methylene blue.
Actually amyloid beta-peptide (Abeta) and neurofibrillary tangles of tau inhibit PMCA. Furthermore lipid peroxidation and 4-hydroxynonenal, which are the most likely and direct causes of POIS also inhibit PMCA.
https://www.sciencedirect.com/science/article/abs/pii/S0304394017306419

[Muon]

The NP-C explained to me that Cialis IMPROVES NERVE CONDUCTION!

Nerve conduction study for POIS?

Edit:
Plus VTA?