POIS paper treatment summary

[Going less Crazy]

Larazotide acetate is on the market for leaky gut, closing tight junctions:
https://www.lvluphealth.com/ultimate-gi-repair/

Larazotide acetate has been something I've been willing to try for a long time now. Too bad it's basically $200 for a month supply. It says it's not meant to be taken forever I think, but that seems to me like it won't be the case. If it wasn't so expensive I'd be willing to try this but I've had so many experiences with sh*tty products that I'm unwilling to fork out this much money for another experiment.

Larazotide acetate is strange though. Supposedly it has an inverse dose type relationship with symptom relief. 1/2mg (500mcg) being effective but higher doses are not. A reason to be skeptical but we'll see the results of this in some time.

[Hopeoneday]

Hi GLC, did you ever try L-glutamine protocol?

[Going less Crazy]

Hi GLC, did you ever try L-glutamine protocol?

I have tried l-glutamine by itself and the side effects made it bad for me. It made me hyper. I guess it increases glutamate in the brain or something? So I could not take that.

[Muon]

Does anyone know a high quality supplement containing Palmitoylethanolamide (PEA)?

[Iwillbeatthis]

Does anyone know a high quality supplement containing Palmitoylethanolamide (PEA)?

This looks good what reason did you want to try it for?

[Muon]

This looks good what reason did you want to try it for?

What looks good?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139331/#sec12-antioxidants-09-00216title
"The pharmacodynamic properties of PEA and those of luteolin appear complementary, suggesting that if administered in combination, they can fight the two main conspirators of chronic diseases: low-grade inflammation and oxidative stress."

[Iwillbeatthis]

The PEA. Thanks I might try some also

[Muon]

The PEA. Thanks I might try some also

It seems they are talking about the ultramicronized form of PEA. Not sure if that even exists as supplement.

[Quantum]

Muon:

"Hello Dr. Rubin,

 A while ago you mentioned that you had treated 2 POIS patients. Are you going to report this eventually in literature? If not, could you share what you have given to these men? Drug name, dose, duration and the subjective amount of relief these men got as a result? And what other meds you have tried in these men which were unsuccessful. I could add that info to this thread:"

 https://poiscenter.com/forums/index.php?topic=3551.0

Dr. Rachel S. Rubin MD, IF:

"Thank you for reaching out!

See our abstract attached that we presented to the SMSNA this year":

Introduction: Postorgasmic illness syndrome (POIS) is a condition that is not well described in the literature. Waldinger and Schweitzer were the first to elaborate on the symptoms, of which the main ones are severe fatigue, intense warmth, and a transient flu-like state. These symptoms have a rapid onset and can last between 2-7 days. The two leading hypotheses regarding the pathophysiology of this condition include immunogenic reactivity to autologous semen leading to a hypersensitivity reaction and a proposition that this is a disorder of the endogenous opioid system. POIS is classified as a rare disorder by the NIH Office of Rare Disease Research, with ~50 cases recorded in the literature over the last 10 years. Historically, patients have been treated with SSRIs, benzodiazepines, and/or antihistamines, but there is no standardized treatment for this condition.

Objective: We describe two patients affected by POIS, their symptomatology, and the treatment methods that were successful in alleviating their symptoms.

Methods: Patient A is a 24 year old male who started having symptoms at age 14. His main symptoms included feeling drained post-orgasm, conjunctivitis, as well as sinus pain, headache, and stomach pains. Patient B is a 32 year old male whose symptoms included post-orgasm fatigue, somnolence, and cold-like symptoms, but the most bothersome was the deep internal fatigue. Both men reported that symptoms persisted weeks after orgasm. Both patients had no significant past medical history, normal genitourinary physical exams, and normal laboratory workups. Patient A was trialed on a combination of pseudoephedrine and hydroxyzine, which led to a marked improvement in his symptoms. He was advised to take 50 mg hydroxyzine nightly and pseudoephedrine 1 hour before orgasm. Patient B was trialed on 25mg tramadol, which he took immediately post orgasm. The tramadol led to a significant improvement of his symptoms, most significantly, the fatigue. Both men were also enrolled in sex therapy as part of their treatment.

Results: We found that the treatment methods used with these two patients support the two leading theories about the etiology of POIS, namely the disorder of the opioid system and the immune system hypersensitivity theory. Jiang et al posited that orgasm consumes large amounts of u-opioids, and in these patients, leads to symptoms similar to those of opioid withdrawal (flu-like symptoms, anxiety, fatigue). Tramadol, a u-opioid agonist, might allow for the repletion of the u-opioids in this specific subset of patients. In a hypersensitivity reaction, the body releases large amounts of histamine, therefore, it is likely that an antihistamine, such as hydroxyzine, would alleviate the associated symptoms. In patient A, who had many allergy-like symptoms, it was logical to trial pseudoephedrine and hydroxyzine.
 
Conclusions: POIS is a rare disorder that requires more research. POIS is likely underrecognized and underreported in the general population and may have more than one etiology. It is important to consider a multi-dimensional approach to treatment, take note of each patient's specific symptoms, and recognize different options of pharmaceutical treatment.

Thanks, Muon for having reached out to Dr. Rubin, so we know what medications she used in those 2 case reports.

[Muon]

Opiesdad improves on: Bupropion and propranolol. Feels worse on SSRI's and LDN.
Hurray improves on Milnacipran while various SNRI's did not do anything for him, feels worse on some (serotonin?):

"There are several drugs which boost norepinephrine, so why is milnacipran any different?"

Well, I have already tried several NRIs:

atomoxetine (Strattera) - uncomfortable feeling during O, brain fog remained
buproprion - made me feel jittery, brain fog remained
ritalin - gave me energy and focus before quickly building up tolerance, did not stop the brain fog
duloxetine - felt like bad flu, could not drive or work, withdrawal symptoms, too sick to accurately gauge brain fog
venlafaxine - felt like bad flu, could not drive or work, bad withdrawal symptoms, too sick to accurately gauge brain fog

The effects of duloxetine and venlafaxine (both SNRIs) were interesting. They made me feel terrible - there was no way that I could take them every day. But my POIS felt a bit different while I was on both drugs.

I read that duloxetine and venlafaxine don't have a powerful effect on norepinephrine at low doses. There was only a substantial norepinephrine reuptake inhibition effect at high doses.

Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819762/

Trying milnacipran, I was surprised  to find that a low one-off dose was sufficient to completely stop the POIS brain fog that I have been accustomed to for so many years. I attributed this to the powerful effect that milnacipran has on norepinephrine reuptake inhibition.

Milnacipran also has multiple reports that it cured the brain fog of fibromyalgia sufferers.

They both feel improvements faster than what the meds are indicated for (usually take weeks for (full) effect).
Is the great common denominator in this story Norepinephrine? Both Bupropion and milnacipran are able to inhibit TNF-alpha as well. Hurray's PE improved -->Milnacipran for Postcoital Cephalgia and Premature Ejaculation (Article can be found under PE in POIS paper archive thread).

Since Bupropion is more effective for Opiesdad than propranolol, it could indicate that there is something going on with dopamine and thus could have consequences for norepi levels (or bupropion is more efficient in raising Norepi?). More about the neuroendocrine response to orgasm can be found here.

(Nor)epinephrine is also a mast cell stabilizer, SSRI's have a high risk of mast cell activation (the reason he feels worse on SSRI's?). Epinephrine can inhibit TNF release from MCs and could explain anti-inflammatory effects of the above meds:

ritalin - gave me energy and focus before quickly building up tolerance, did not stop the brain fog

Ritalin can also raise DA and NE in brain if I'm not mistaken. Overlap with this?:

I first managed it with Dextroamphetamine which is used for ADHD but now not even that helps

From cocaine thread:

From tuning the brain:
"Androgens such as testosterone increase the secretion of dopamine, probably by decreasing the activity of the dopamine transporter. Ritalin and cocaine also have this action. Androgens also increase DA by interacting with NO"

"Adderall works both by inhibition of dopamine reuptake and by increasing secretion of norepinephrine and dopamine. Inhibition of dopamine reuptake by blocking the plasma membrane dopamine transporter is the primary mechanism of action of methylphenidate (MPH, Ritalin) and cocaine."

Nitroglycerin may work as well. I bet this is one of the possible pathophysiologies of POIS.

Should mention that in the 2020 case study reporting an effective treatment of a single patient using TRT, the report mentions in the history that the patient had not had good results with Wellbutrin among other therapies, so it won't work for everyone I guess.

He is talking about #29 (mind you numbers may change): https://poiscenter.com/forums/index.php?topic=3551.0
If hCG works for patient from article #29 then why isn't Bupropion when considering DA?: https://poiscenter.com/forums/index.php?topic=3551.msg38085#msg38085

IDK how significant is this but according to wikipedia: "Recently, levomilnacipran, the levorotatory enantiomer of milnacipran, has been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for beta-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease."

beta-amyloid plaque formation causes irregular ion channel activity and BACE-1 is triggered by cytokine release.

Relationship Between Amyloid Precursor Protein in Seminal Plasma and Abnormal Penile Sympathetic Skin Response in Lifelong Premature Ejaculation

Compare with Milnacipran for Postcoital Cephalgia and Premature Ejaculation.

Edit:

Hi Muon,
Regarding your post on Bupropion :

Opiesdad improves on: Bupropion and propranolol. Feels worse on SSRI's and LDN.
(...)

You may want to read this exchange on reddit (user TheLooza is Opiesdad), for other hypotheses :
https://www.reddit.com/r/POIS/comments/mkeh4n/wellbutrin_appears_to_have_cured_my_worst_symptoms/gtjjz8z/?context=3
and https://www.reddit.com/r/POIS/comments/mrp51k/noepiephrine_deficiency_and_noepiephrine_reuptake/guwbi6p/?context=3

[Muon]

https://youtu.be/LqLSKUPAjsI?t=234

"Medial preoptic area (MPOA) and medial amygdala are sensitive to Testosterone (hormonal input)"