Ivermectin - anyone used it?

[Laotzu1980]

Hi,

Has anyone used Ivermectin for POIS?

I am testing it at the moment, not for POIS, but to prevent COVID, which trials suggest it does quite well.

Anyone tested it for POIS? It was mentioned in one other thread.

[Progecitor]

I also wrote about ivermectin, but I only wanted to point out that some of its effects could be in connection with the endocannabinoid system. Unfortunately it is not readily available in my country and I don't know if I am ever going to be able to test it.
I also read through your posts and your case definitely seems different than mine:
- Clonazepam, a Diazepam analog, actually increased my brain fog.
- Venlafaxine worked for me, but not in your case.
- B3 and an L-Theanine seems to work for me, but not in your case.
- Clomipramine an a1 adrenergic receptor antagonist was not beneficial for me while amitriptyline which has a similar property was somewhat effective for you.
Have you ever tried paracetamol, taurine or curcumin (turmeric) with any success or adverse effects?
Do you have any food "allergies" at all, because you didn't mention anything like that?
You could also try saffron tea if you really have brain fog. If you do this please report about this even if it doesn't work as it could indicate that some brain fog is not saffron (FAAH inhibitor) responsive.
If you are really up to experimenting you may also want to test metformin.
I have just read some article about it the other day which claim that metformin possibly prevents severe COVID-19 infection.
https://www.news-medical.net/news/20210611/Metformin-prevents-pulmonary-or-lung-inflammation-in-animals-infected-with-SARS-CoV-2.aspx
https://www.frontiersin.org/articles/10.3389/fendo.2020.600439/full?utm_source=S-TWT&utm_medium=SNET&utm_campaign=ECO_FENDO_XXXXXXXX_auto-dlvrit
Metformin also proved detrimental for some POISer (Mr RABA), however it may be beneficial for some CFS patients.
https://poiscenter.com/forums/index.php?topic=3830.msg40877#msg40877
Unfortunately the other POISers who tried metformin didn't clearly state if it was beneficial or not, so this may be not a sound advice.

[Progecitor]

You could also check my research thread for some info:
https://poiscenter.com/forums/index.php?topic=3733.15
(ctrl+f: benzo)
In your case GABA(A) and AKR1C1 could be implicated.
AKR1C1 enzymes inactivate progesterone and allopregnanolone. Allopregnanolone can influence mood, memory, cognition, neuroendocrine and reproductive behaviors. Allopregnanolone (5a-THP) is an important endogenous agonist and positive allosteric modulator of GABA(A).
Benzodiazepines are GABA(A) positive modulators and they also inhibit AKR1C1 quite potently, thus preventing the inactivation of allopregnanolone.
To test this theory you could try a combination of taurine (GABA(A) agonist) and apigenin (GABA(A) positive modulator and also a weak inhibitor of AKR1C1).
Of course this is only a recommendation and may yet turn out to be false, so it is up to you if you take these into consideration.

[swell]

Ivermectin is not believed to cross the blood brain barrier in mammals i.e. humans, so if you are referring to a research on parasites or MDR gene knockout mice, its effect on the CNS endocannabinoid system, that would not be applicable to us.

So recently Ivermectin has become a politically controversial subject and  observing this saga has bothered me, but I learnt some things as well:

a) Medical profession is much more political than your other professions. Do not be fooled.
b) Research has become political tools for various factions.  On the one hand is the richer Pharmaceutical aka Global establishment (anti-Ivermectin, anti-Cloroquine/hydroxy).  On the other hand are the less-money Pro-Ivermectin/Hydroxycloroquine groups.
c) I feel very bothered since I have observed both groups to distort facts and I believe this is impacting common persons life/health and science in general.  I would be tempted to side with the less-money Pro-Ivermectin/Hydroxy group (at least they are fighting the big bad thugs) however I get appalled also when they use misleading tactics.
d) In general, you will find Covid trials/research that shows Ivermectin as very efficacious and you will find trials that shows Ivermectin with no effect on Covid.  What is appalling is anti-Ivermectin trials reek of corrupt money biases, and pro-Ivermectin trials to me demonstrate weaknesses that question their legitimacy. 

So enough of my rant, to your question, I have used Ivermectin, and I am neutral about it.  I have seen people die from Covid despite taking Ivermectin, and I have seen people get better after taking Ivermectin.  I am still alive and did not get sick, though I did get Tinea Fungus, whether through Ivermectin or through vaccination, I cannot tell.  I try to keep an open-mind, and question the prevailing all-conclusory assumption that Fungus indicates a weakened immune system and the intervention a failure.  I believe it could also be positive, meaning that despite defective immunity to begin with, the intervention you took (Ivermectin or Vaccination) it heightened your immune response so as to expel the fungi pathogen which previous hid well in your body, but now it could no more, and is desperately trying to get out through your skin.  I would be interested to hear all of your views on this theory

I do have an abnormal trait, to observe effects of something on myself.  After I took Ivermectin, the one thing I could observe was that:
- Up to 3-4 days, I had intense hungers and ravaged on food. 
- I am already hyper-mobile (elastic/flexible joints), and I felt to have even increased hypermobility for about a week.
- I was hoping to see worms at least in my stool, but I did not notice anything un-usual there.
Hope this helps!

I also wrote about ivermectin, but I only wanted to point out that some of its effects could be in connection with the endocannabinoid system.

[Laotzu1980]

Oh dear, don't get me started on Ivermectin and COVID. If any of you listen to Bret Weinstein's "Dark Horse" podcast, you'll understand my frustration in discussing it.

I took it as a prophylaxis (to prevent COVID) the week before flying home to Australia, and so far all is well. I am in quarantine now, and loving every minute of it. If you can't go out, journey within. 🙂

Thank you for that info Progecitor and Swell. I'm currently testing Milnacipran this week - although the Ivermectin is in my system from taking 2 doses last week, but let's see how it goes with the Milnacipran.

[Progecitor]

Ivermectin is not believed to cross the blood brain barrier in mammals i.e. humans, so if you are referring to a research on parasites or MDR gene knockout mice, its effect on the CNS endocannabinoid system, that would not be applicable to us.

I don't think ivermectin needs to bypass the blood brain barrier to have an effect on POIS. Of course it may not have any effect on POIS for all we know, but a possible effect is more likely to be in connection with its proposed antidiabetic property which stems from ivermectin's interaction with Farnesoid X receptor (FXR) and PPARG. However studies have conflicting evidence on whether ivermectin stimulates FXR or has an antagonistic effect on it. Your increased appetite may point to the latter (antagonistic activity) as FXR deficiency is known to increase energy expenditure. PPARG is a factor that I am currently pondering about, but it is by all means not a straightforward issue.

Farnesoid X receptor (FXR) has important roles in maintaining bile acid and cholesterol homeostasis. Here we report that the antiparasitic drug ivermectin is a ligand for nuclear FXR. We identify ivermectin using a high-throughput compound library screening and show that it induces the transcriptional activity of the FXR with distinctive properties in modulating coregulator recruitment.
The binding of ivermectin to g-aminobutyric acid receptors increases the releasing of inhibitory neurotransmitter g-aminobutyric acid in parasite, resulting in the blocking of the transmission of nerve signals, which leads to nerve palsy, loss of contractility of the muscle cells and, ultimately, parasite death.
Farnesoid X receptor (FXR), also known as bile acid receptor, is a member of the nuclear hormone receptor superfamily that is highly expressed in mammalian liver, intestine, kidney and adrenal gland.
Remarkably, ivermectin displays antidiabetic activities by reducing blood glucose and cholesterol levels, and also by improving insulin sensitivity in an FXR-dependent manner.
The distinctive functional profile of nuclear receptors in response of various ligand binding is largely determined by the selective usage of transcriptional coregulators, as ligand-specific recruitment of coregulators ultimately controls transcriptional output of direct and indirect target genes. Thus, ligand-bound FXR may show diverse pharmacological functions depending on the specific binding of coregulators induced by different ligands. The results from both biochemical AlphaScreen assay and cell-based reporter assay showed that ivermectin is a partial agonist for FXR owing to its much less capability in recruiting coactivators compared with typical full agonist GW4064.
Thus, the selective usage of coregulators may contribute to the unique characteristics of ivermectin in modulating FXR activity in metabolism.
https://www.nature.com/articles/ncomms2924?origin=ppub

Ivermectin treatment also significantly modulated the mRNA expression of key markers in adipogenesis, fatty acid synthesis, uptake, and oxidation, and enhanced the gene expression of two subunits of the glycine receptor (GlyR). Specifically, the protein levels of peroxisome proliferator-activated receptor gamma (PPARG), CCAAT/enhancer-binding protein alpha (C/EBPa), and acetyl-CoA carboxylase (ACC) were reduced. Interestingly, the suppression of TG accumulation by ivermectin was partially abolished by rosiglitazone, a specific PPARG agonist, but Z-guggulsterone, a selective FXR antagonist, failed to rescue the ivermectin-induced effect on adipogenesis.
In conclusion, ivermectin inhibits adipogenesis of 3T3-L1 preadipocytes partially via PPARG and GlyR-dependent, but not FXR-dependent, pathway.
https://www.sciencedirect.com/science/article/abs/pii/S0278691519303655

Furthermore, using bioluminescent cell lines expressing transcription factors, we have demonstrated that ivermectin was not a CAR, PXR or AhR ligand. However, the role of other transcription factors, including nuclear receptors, in the ivermectin-induced regulations cannot be discarded since number of them such as PPARG, as well as Nrf2, are described to be involved in efflux ABC transporters transcriptional regulation.
https://hal.archives-ouvertes.fr/hal-01191347/file/biochem%20pharmacol%20laila_%7B107619A4-A255-4B3E-9C13-F27B977EE4D4%7D.pdf

Studies using FXR deficient mouse models showed both beneficial and adverse effects of FXR deficiency. Zhang et al. reported that compared to wild type controls, female Fxr-/- mice had increased energy expenditure and were resistant to diet-induced obesity. On the other hand, several studies have demonstrated that Fxr-/- mice were more susceptible to liver injury induced by chemicals including bile acids, and developed severe non-alcoholic steatohepatitis (NASH)-like liver pathology, especially on a high-fat diet. Studies also indicated that FXR deficiency deregulated intestinal innate immunity, altered neurobehavior and promoted tumorigenesis in mice. In addition to FXR, constitutive androstane receptor (CAR), liver X receptor (LXR), and pregnane X receptor (PXR) also heterodimerize with the RXR and regulate transcription of genes involved in bile acid and lipid homeostasis, complicating interpretation of the results generated with FXR.
In addition, luciferase reporter gene assays were employed to explore compound selectivity against nuclear receptors (e.g., CAR, LXRa, and PXR) that also heterodimerize with the RXR and coordinate with FXR to regulate subsets of downstream effectors and signaling pathways involved in energy and xenobiotic metabolism. Avermectin- and milbemycin-based drugs (e.g., ivermectin and moxidectin) not only interacted with FXR but also CAR, LXRa, and PXR. The antiparasitic drug ivermectin was previously shown to stimulate FXR activity and to inhibit CDCA-induced FXR activity in cell-based and biochemical assays. Ivermectin was also shown to decrease cholesterol and serum glucose levels, and improve insulin sensitivity in mice by stimulating FXR activity, suggesting the potential use of ivermectin or its analogs for diabetes treatment. However, the potential in vivo outcomes of ivermectin’s FXR antagonist activity have not been well characterized. All avermectins tested in our experiments showed antagonistic activity to FXR, CAR, LXRa, and PXR.
https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S0041008X1630326X

FXR has also been found to be important in regulation of hepatic triglyceride levels. Specifically, FXR activation suppresses lipogenesis and promotes free fatty acid oxidation by PPARA activation. Studies have also shown the FXR to regulate the expression and activity of epithelial transport proteins involved in fluid homeostasis in the intestine, such as the cystic fibrosis transmembrane conductance regulator (CFTR).
Activation of FXR in diabetic mice reduces plasma glucose and improves insulin sensitivity, whereas inactivation of FXR has the opposite effect.
Farnesoid X receptor has been shown to interact with Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and Retinoid X receptor alpha.
https://en.wikipedia.org/wiki/Farnesoid_X_receptor