POIS paper treatment summary

[Muon]

Interesting. If I take anti-histamines with pseudoephedrine they are more effective than anti-histamines alone (ie Allegra-D). Pseudoephedrine is a norepinephrine releasing agent.

"Pseudoephedrine acts on alpha- and beta2-adrenergic receptors" Ref

Activation of beta2-adrenergic receptors on mast cells is the primary pathway for adrenergic agents to inhibit mast cells.

Table 1 and chapter 5: Neuroendocrinology of mast cells: Challenges and controversies.

Patient A was trialed on a combination of pseudoephedrine and hydroxyzine, which led to a marked improvement in his symptoms.

And/or pseudoephedrine counters vasodilation which is induced by histamine:

https://en.wikipedia.org/wiki/Histamine#Vasodilation_and_fall_in_blood_pressure

Vasodilation and fall in blood pressure
"It has been known for more than one hundred years that an intravenous injection of histamine causes a fall in the blood pressure.[18] The underlying mechanism concerns both vascular hyperpermeability and vasodilation. Histamine binding to endothelial cells causes them to contract, thus increasing vascular leak. It also stimulates synthesis and release of various vascular smooth muscle cell relaxants, such as nitric oxide, endothelium-derived hyperpolarizing factors and other compounds, resulting in blood vessel dilation.[19] These two mechanisms play a key role in the pathophysiology of anaphylaxis. "

https://en.wikipedia.org/wiki/Pseudoephedrine#Mechanism_of_action

"Pseudoephedrine is a sympathomimetic amine. Its principal mechanism of action relies on its direct action on the adrenergic receptor system.[15][16] The vasoconstriction that pseudoephedrine produces is believed to be principally an alpha-adrenergic receptor response."

[Vandemolen]

Massive paper about CBD:
Immune Responses Regulated by Cannabidiol (2020)

Some folks can resolve their POIS completely with CBD oil, like Vandemolen. Aside from mast cell stabilisation via CB1/2, it can act through other receptors; "These studies show that CBD acts through the adenosine A2A receptor, especially in microglial cells." Milnacipran in the case of hurray could also act on microglia.

CBD could be inducing Tregs just like TRT, see this post and articles below:

Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation (2017)

Cannabidiol (CBD) induces functional CD4+ CD25+ FOXP3+ Tregs (2016)

Response to CBD could differ depending on the level of T cell activation.

Too bad for me that cbd does not work for me anymore. I think I am allergic for things that go with the cbd. I am also allergic for vitamin D.

[Muon]

Dumping some half baked info here, will maybe take a look at it later. Could a subgroup of POISers be categorized as certain responders based on this diagram?

https://forums.phoenixrising.me/threads/dr-jay-goldsteins-rapid-remission-me-cfs-treatments.34516/page-6#post-582561

Lot of stuff in the diagram is used by POISers.

I was looking at Goldstein diagram earlier. And it seems that Nicotine (dopamine agonist) gives me a bad reaction And Coffee (an Adenosine receptor stimulant) slightly improves my symptoms. So I don't know what's xxxxxx up, my dopamine receptors or Benzodiazepine receptors.

I think you meant to say that it increases adenosine, It's an antagonizer: Caffeine and adenosine. https://thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03_m_par/i_03_m_par_cafeine.html#drogues. Is a weak non-selective PDE inhibitor. Also got acetylcholinesterase inhibition properties.

Mestinon had no effect on Nas. Cigarette smoke induced symptoms in him (discussed this is endothelial dysfuncton thread). "Nicotine and cigarette smoke both induce the expression of liver enzymes (e.g., certain cytochrome P450 proteins) which metabolize drugs, leading to the potential for alterations in drug metabolism" https://en.wikipedia.org/wiki/Nicotine#Drug_interactions
I'm not interested to dive into this p450 rabbit hole: https://en.wikipedia.org/wiki/Cytochrome_P450#Other_specific_CYP_functions
But it could mess up hormone metabolism, already discussed in the case of Heather in the women's thread. And fatty acids and eicosanoids metabolism which is involved in PLA2/AA cascade inflammation.

Coffee dose dependent is benificial to HOD as benzodiazepines.

Takedrugstoletgo had succes with dextroamphetamine.

Benzo's and nootropics had some effect on my brother's symptoms.

Heather and demo felt awful on progesterone/norethisterone but good on testosterone (they aren't ketamine responders, rather the opposite, and/or dopamine responders).

A few individuals used viagra and PDE4.

Some do improve on mestinon (pyridostigmine)

So far the pyridostigmine (mestinon) isn't doing anything yet in my case. Mestinon increases acetylcholine availability. I feel bad on alcohol, a NMDA receptor blocker, it also blocks or activates nAChRs depending on subtype I believe.

Aren't the selective alpha1 blockers used in Reisman's paper also PDE5 inhibitors? These folks may feel worse on naphazoline. There are PDE inhibitors in the diagram.

I've also read that Midodrine is used for peripheral denervation in dysautonomia.

Me and Ironfeather could be trembling after exercise, isn't this effect also seen in alcohol abusers?

[Iwillbeatthis]

I found nicotine gives me brain fog when taken normally, but when I was at a party and having a bad reaction to alcohol, a cigarette seemed to fix things, I also remember at a football game I watched I was feeling foggy and bad then tried nicotine gum and it helped my symptoms again.

[Muon]

Agmatine sulfate increases BDNF and eNOS, I ordered some and it came today so I will test it out

Any result?

[Iwillbeatthis]

Agmatine sulfate increases BDNF and eNOS, I ordered some and it came today so I will test it out

Any result?

Nope, I tried inside POIS it did nothing, then tried outside of POIS when I was feeling foggy and tired, it did clear the brain fog and give me energy but every time it wears off it induces a headache and I feel strange. So I'm not gonna use it anymore and its probably a bad idea for me to take arginine related things as they may feed viruses + increase spermidine production. The guy who used the agmatine for his autistic kid combined it with MCT oil though.

I got Sulforaphane from the same company so will try that next, I got them both for really cheap.

[Muon]

Hello, I have started taking Zinc Picolinate 40mg and I have noticed a slight improvement in my POIS symptoms (a bit more alert and my psoriasis is not so bad).

Could this mean that my POIS is hormone-related given Zinc is linked to testosterone, etc? Is there anything else I should try alongside Zinc given I have seen some improvements with Zinc?

Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity

"We observed that IFN-g and IL-8 cytokines were elevated in psoriatics and correlated with parameters of disease severity while IL-10 and IL-12 were decreased."

Susceptibility-associated genetic variation at IL12B enhances Th1 polarization in psoriasis

Tuning the brain:
"If NGF levels are too high, a phenomenon called apoptosis occurs. Apoptosis is associated with cell death. Using zinc in fairly
physiologic concentrations attenuates the apoptosis induced by NGF.

Zinc can block NMDA receptors acutely and can also induce a Src family-mediated (tyrosine kinase) up-regulation of NMDA-receptor
function.

The NMDA receptor has numerous modulatory sites. These include those for ketamine, polyamines, zinc, magnesium, pH, redox, glycosylation,
glycine, heparin, dextromethorphan, and dynorphin."

...Sounds like an 'abnormal' endogenous process due to orgasm that can be triggered by an exogenous substance, in this case semen...

...From second paper:
"Human seminal plasma contains very high concentrations of prostaglandins when compared to other bodily secretions. It is now apparent that PGE2, 19-hydroxyprostaglandin E1 and 19-hydroxyprostaglandin E2 are the three major prostaglandins in human seminal plasma, each being present in millimolar concentrations..."

I think it's the prostaglandins in the semen that cause this. Or it could be caused by the polyamines (spermine, spermidine).

"Spermine is a nociceptive substance. Its algogenic effect may possibly be antagonized by Ca2+-channel blockers, SAMe, morphine, and various NMDA antagonists, especially those acting at the polyamine site.

Spermine stimulates Casein Kinase II (CKII) and up-regulates NMDA-channel activity, probably through coupling to the spermine modulatory site on the receptor."

Several agents block the spermine site:

Nylidrin, isoxsuprine, acamprosate, ifenprodil, eliprodil, and haloperidol.

[Muon]

From tuning the brain (Dr. J. Goldstein):
The situation in which synaptic fatigue is most obvious is that of sexual arousal and ejaculation in the male with a neurosomatic disorder. Some males relapse after ejaculation. A few relapse, but in a different, milder way, after sexual arousal.

SYNAPTIC FATIGUE

Synaptic fatigue is a term that used to make me think an axon terminal had been repetitively stimulated so frequently that its supply of transmittercontaining vesicles in the appropriate position at the membrane to be released ("docked") could not keep up with the demand. Such a process is termed "frequency-dependent depression." It occurs over minutes of repetitive firing and recovers slowly, eventually reaching an equilibrium with transmitter packaging into recycled vesicles. In the case of the catecholamines, using this scenario, there could also be

• decreased precursor (phenylalanine and tyrosine--even L-dopa);
• insufficient activity of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine biosynthesis;
• low levels of the various cofactors for the enzyme chain DA and NE;
• impaired axonal transport to the terminal;
• impaired manufacture, transport, and reuptake of DA and NE vesicles at the terminal;
• problems with the Ca2+ channels (which open to initiate vesicle release); and
• dysregulation of communication in the postsynaptic neuron

[Muon]

Too bad for me that cbd does not work for me anymore. I think I am allergic for things that go with the cbd. I am also allergic for vitamin D.

Why did it work for you in the first place? Why don't doctors try to figure this out? I gave you a book. Open it and search (CTRL-F) for 'canna'. It affects so many things. Increases serotonin, inhibits adenylyl cyclase, affects opioids, dopamine, and the list goes on. You need other substances to test potential mechanisms of CBD one by one.

[berlin1984]

Method of POIS relief central hub

Wow, great compilation..

[Muon]

https://www.dinet.org/forums/topic/31629-mechanism-of-choline-deficiency-and-membrane-alteration-in-pots/?tab=comments#comment-285360

[demografx]

...If anyone wants to go through the 1000+ pages on Nakedscientist looking for cases describing treatment methods then be my guest, I'm not going to do that. Or perhaps some do remember POISers describing treatment/relief methods on certain pages, in that case dump the links here plz.

A Naked Scientists [aka TNS] forum search can be Googled easily: just put in the search term you’re looking for, and then “POIS” (for TNS’ POIS thread), plus the URL/link for TNS.

For example, if you’re looking for TNS posts that include testosterone, put this in the dialog box @ Google:

testosterone POIS https://www.thenakedscientists.com






TNS is a valuable historical universe of
20,000+ POIS posts starting in 2007. I was the main moderator/administrator. Until “Daveman” and I split from TNS to create this forum, POISCenter.com. I am still the main admin at TNS/POIS, however it has become posting-inactive recently, although it’s still very useful as a repository with a wealth of early POIS history.

Go visit!
https://www.thenakedscientists.com/forum/index.php?topic=6576.0

 

[Muon]

POISers on ketodiet:

Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism? (Hippocampus)

https://forums.phoenixrising.me/threads/second-study-confirms-neuroinflammation-in-me-subcortical-brain.80923/page-3#post-2295932

NAD, Niacin:
https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide

NAD+ protects against EAE by regulating CD4+ T-cell differentiation (NAD+ promotes IL-10 under Th1 conditions)

NAD+ regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4+ CD25+ Foxp3+ T cells independent



Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body beta-hydroxybutyrate

"Exercise induces DBHB levels in the hippocampus"

BDNF mediates adaptive brain and body responses to energetic challenges

BDNF plays a role in stress sensitivity btw.

TRT:
Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway

" In rat aortic strips, 5–20 min treatment with physiological concentrations of testosterone significantly increased nitric oxide (NO) production. The
rapid action of the steroid was suppressed by the presence of an androgen receptor antagonist (flutamide). We obtained evidence that the enhancement in NO synthesis was dependent on the influx of calcium from extracellular medium, because in the presence of a calcium channel blocker (verapamil) the effect of testosterone was reduced."

Effects of opioid (tramadol) treatment on testicular functions in adult male rats: The role of nitric oxide and oxidative stress

Comparison of the Efficacy of Tramadol and Paroxetine in the Management of Premature Ejaculation

Caffeine's Vascular Mechanisms of Action

Nitric oxide and major depression

Nitric Oxide Modulators: An Emerging Class of Medicinal Agents

Recent developments in nitric oxide donor drugs

[Muon]

The patient has a history of irritable bowel syndrome (IBS) well-controlled on loperamide.
Trial of cetirizine, after 4 weeks (orgasm once per week): significant improvement in abdominal cramping and reduction of diarrhea

Loperamide is an opioid-receptor agonist and acts on the mu-opioid receptors in the myenteric plexus of the large intestine.

https://en.wikipedia.org/wiki/Loperamide#Mechanism_of_action

Tried naltrexone (LDN - 4.5 mg split in half, once daily) for two weeks and it actually increased my brain fog and other POIS-like symptoms and this weeks removed from last orgasm.  Very similar reaction to when I tried provigil for a period. It's a no go for me, sadly.

Naltrexone and its active metabolite 6?-naltrexol are competitive antagonists at the mu-opioid receptor (MOR)

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

As of 2017, the therapeutic mechanism of action of modafinil for narcolepsy and sleep-wake disorders remains unknown.[35][36] Modafinil acts as an atypical, selective, and weak dopamine reuptake inhibitor which indirectly activates the release of orexin neuropeptides and histamine from the lateral hypothalamus and tuberomammillary nucleus, respectively all of which may contribute to heightened arousal

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

Loss of muscle tone:
https://en.wikipedia.org/wiki/Orexin

[Muon]

Methylene blue acts directly on the nervous system, where you notice the problems. The nervous system governs the intestine, inflammation, hormones, metabolism, everything. You'll have to play around with the dose and see what works for you. I took 3-4mg yesterday and to my pleasant surprise, NO POIS. I'll keep you guys updated if this continues to work. There is a big thread on longecity forum about it if you want to check it out, but to my understanding, those guys are waaay underdosing it.

Guanylyl cyclase inhibitor:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab10/

Role of nitric oxide production in anaphylaxis and its relevance for the treatment of anaphylactic hypotension with methylene blue

Methylene blue for clinical anaphylaxis treatment: a case report

Nitric Oxide release during POIS activating Guanylyl cyclase in this case?