FDA Approves Allopregnanolone As A Fast-acting, Long-lasting Antidepressant

[charlie]

Does Ray Peat suggest an optimal dose Palmitoylethanolamide? Or does anyone know what is a good dose to start out with?

 

[Sativa]

Or does anyone know what is a good dose to start out with?

From the looks of it, the range is 300 to 1200 mg.
My use is for general maintenance and relaxation, 200mg pure powder directly in mouth is my approach. But I'm sure combined with a fat/food might facilitie things.

This stuff is entirely non-toxic... I'd have no qualms taking 2g or even 5g... but only if i wanted some serious anti-inflammatory, analgesic, relaxing, calming effects.

 

[Sativa]

I'd have no qualms taking 2g or even 5g... but only if i wanted some serious anti-inflammatory, analgesic, relaxing, calming effects.

I took 1 gram last night, instead of smoking some cannabis & tobacco. The effects were very therapeutic, and today i feel refreshed.

 

[Sativa]

A little off topic but related to squalane..... @Sativa do you think it is an ideal carrier oil? For essential oils and other compounds? Moreso then olive oil?

perhaps an expensive one...
I use EVOO or pure organic alpha-tocopherol aka vit e oil as my carriers. I have dissolved some things in coconut oil, such as Borneol or Curcumin. The Palmitoylethanolamide I got dissolves quite well in EVOO, it has a sufficiently small particulate size (no, it's not the 'ultra micronised' PEA that is super expensive)

 

[LeeLemonoil]

Patchouli alcohol activates PXR and suppresses the NF-κB-mediated intestinal inflammatory. - PubMed - NCBIHere is one for @Sativa

EO-constituents that activate PxR

Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver. - PubMed - NCBI

 

[LeeLemonoil]

And this. Terpenes activating PxR might prevent bacterial translocation. This claims that’s a general action of activated PxR by strengthening tight jumction

Pregnane X receptor activation by its natural ligand Ginkgolide-A improves tight junction proteins expression and attenuates bacterial translocation ... - PubMed - NCBI

@haidut and others think that bacterial translocation is involved in many diseases, Bowel inflammatio and even autoimmune stuff

 

[Sativa]

activating PxR might prevent bacterial translocation. This claims that’s a general action of activated PxR by strengthening tight junction

interesting...thanks for that.

A link to p-glycoprotein... Progesterone, piperine & PXR modulate p-glycoprotein!

P-glycoprotein, the most extensively studied transporter, functions as a biological barrier by extruding toxins and xenobiotics out of cells.
P-glycoprotein plays a significant role in drug absorption and disposition. ​

Note: OTC piperine from black pepper inhibits p-glycoprotein:

Piperine, an alkaloid and a major ingredient of black pepper (Piper nigrum/longum) has been reported to impart P-gp inhibitory activity, as well as antitumor, antioxidant, antimicrobial, bio-enhancer and hepatoprotective activity​

Progesterone inhibits p-glycoproteins:

Cells acquire cholesterol through endogenous synthesis and through receptor-mediated uptake of cholesterol-rich low density lipoprotein (LDL). Esterification of LDL-derived cholesterol is catalyzed by acyl-CoA:cholesterol acyltransferase (ACAT) in the endoplasmic reticulum (ER). Progesterone inhibits esterification, and, although the mechanism of inhibition is not completely understood, this inhibition results from progesterone's ability to inhibit the activity of multiple drug resistance (MDR) P-glycoproteins (P. DeBry and J. E. Metherall, submitted for publication).​

-

PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line.
Abstract
PURPOSE:
The development of multidrug resistance (MDR) is one of the major limitations in the treatment of cancer. Induction of P-glycoprotein (Pgp) has been regarded as one of the main mechanisms underlying anticancer drug-induced MDR. Since the induction of Pgp is (in part) regulated by the pregnane X receptor (PXR), the ability of several widely used anticancer drugs to activate PXR-mediated Pgp induction was investigated.​

A PXR link to bile acids & important detoxification pathways...

Lithocholic Acid (LCA) is a secondary bile acid; toxic and can destroy the liver.
A change in our gut bacteria, toxins, glyphosate, vaccine injury, infections, leaky gut and many other things can change our hormone levels. This can inhibit the ability for the liver to sulfate bile acids.
The pregnane X receptor has been found to be inhibited in those with bile blockage disorders.
Those with upregulated PXR have been found to be protected from the negative effects of LCA.
source: leaky gut – Lee's Stuff​

 

[Mauritio]

Has anybody tried PEA ? It seems like a very promising substance.
It lowers histamine and nitric oxide . It inhibits COX-2 . It increases allopregnanolone .
And it's currently in clinic trials for the treatment of lung inflammation from covid 19 , so it might still be good time to try it before it becomes a prescription medication.

 

[wildworld1992]

I'm sorry but I am having trouble understanding that quote. (I have a bad headache, which is unfortunately quite common for me)

So PEA is a reliable way to increase allpregnenalone? Or to activate the same neurological pathways?

I ahve post finasteride syndrome and would definitely like to try some allopregnanolone because pregnanolone and 5adhp have helped me in the past. Anything that increases GABA is helpful, it seems. Too much can cause a headache, though.

Did you try PEA and Agmatine?

 

[Advocate2021]

Based upon recommendation from a forum member in a thread i started for help with severe chemical hypersensitivity i have been living with for 30 years at least and which i realize coincides with being put on estrogen for 12 years from 17 - 28, I ordered the Nooropics PEA powder and just received it yesterday. Around 3 30 pm yesterday i took a quarter tsp (400 mg) under my tongue and was completely knocked out within 20 min and slept until 5. Then went to gym as had been meaning to before i slept and was aware how different i felt- like my whole system had been given a sedative. I still have this feeling a bit today but i think this means some sort of reset is happening. think i will take it tonight and continue in evenings due to the powerful sedative effect but i am so excited about this and am optimistic this could be the answer to this life long issue i have been struggling with despite resolving every other health issue. It has baffled me so because I got so healthy and strong otherwise- could not figure out where this was coming from but it has plagued me daily for at least 30 years without reprieve no matter what i tried. Even tried hypnosis and brain techniques- nada for the physical symptoms but made me calmer when i reacted to things at least lol. My theory that developed through conversing here on my thread is that the estrogen poisoning for all of those years early in adulthood made me hypersensitive to anything that is the slightest bit estrogenic and in fact everything i react to is estrogenic. so reading about PEA, it seems this might mitigate that sensitivity via its mechanisms of action. only had one dose but it was profound. will continue to report here. Thank you to @PeskyPeater who suggested this for me on my other thread.

 

[Mister]

PEA also seems promising for Post finasteride syndrome.

 

[Brandin]

Perhaps. Such thinking style is foreign to me since nothing actually happens 'to' me, as this would be quite a disempowering mentality for me to choose.

Borther you shouldnt need to ignore a trith to feel good. The guy is saying something that is true. He is saying it possibly cause he wish to fix it not cause he is feeling stuck and helpless…