Palmitoylethanolamine (PEA) Supplement--Any Experiences?

[managing]

Any experiences with PEA? Lots of solid research on pain, neuropathy being improved considerably. Its action appears to be through inhibition of mast cells releasing histamine.

Any contrary thoughts?

Experiences?

Peat ever say anything about it (I can't find anything)?

 

[managing]

Nobody?

 

[Dave Clark]

I have heard it works via the cannabinoid receptors of some sort. I have tried it for pain, but did not really see any significant difference. Most of what I hear is that it works for some real well, and others not at all. I am interested in the anti-allergy potential, but I don't know how well that works with the PEA. Palmitoylethanolamide (PEA) Powder
If you read testimonials from people, not just this link, it seems it takes a while for benefits to be felt, so I wonder if people are not just giving up on it too soon? I think it maybe has benefits that are subtle, but important.

 

[jb116]

Same here. I tried it and had my mom experiment with it. I felt nothing and she developed a mild headache that went away when she stopped it after 2 days.

 

[managing]

Thanks. I'm most interested in its anti-catecholamine effects. I have some on the way. Not sure when i'll experiment with it as I am going to be traveling. But when I do, I'll post here.

 

[Sativa]

PEAmide is pretty dam good therapeutically useful stuff, with novel properties. Fat soluble.
Increases Allopregnanolone!
I made a post detailing it's Prop-Peat properties

 

[Dave Clark]

PEAmide is pretty dam good therapeutically useful stuff, with novel properties. Fat soluble.
Increases Allopregnanolone!
I made a post detailing it's Prop-Peat properties

Where? Not much comes up on a search on this forum, at least when I plugged in 'palmitoylethanolamide'.

 

[shine]

I tried it when I was still quite sick and fatigued. It had a great effect on brain fog, really cleared up my brain and improved thinking/cognition and mood. But I would get a weird feeling in my chest/heart and stopped using it. Maybe because it has an effect on PPAR's, thus changing heart energy metabolism, and I was heavily relying on burning PUFA for energy at the time.

 

[Sativa]

One starts here:
FDA Approves Allopregnanolone As A Fast-acting, Long-lasting Antidepressant

 

[managing]

One starts here:
FDA Approves Allopregnanolone As A Fast-acting, Long-lasting Antidepressant

Ah, yes. I had the same response--thought you meant a thread on PEA. That is a good thread though, read it before I created this one.

 

[managing]

I went back and reread that thread. I think I had only read the first page previously.

You (@Sativa ) also mention agmatine. I see one big difference though. Agmatine gave me (after a couple of weeks) a seriously elevated catecholamine issue. Allopregnanolone (and DHEA-S) can both elevate catecholamines significantly (by inhibition of tyrosine reductase). But PEA simultaneously inhibits mast cell degranulation. So, although it also raises allopregnanolone, it doesn't seem (so far) to give me catecholamine issues.

I was totally bummed when this started happening with agmatine because otherwise it had been amazing.

I assume the difference is that PEA simultaneously inhibits histamine. It doesn't make me feel super confident the way that agmatine did, but it does elevate mood mildly.

 

[managing]

Here is a really comprehensive lit review. Some things I haven't come across elsewhere such as normalizing blood pressure, blood glucose, and insulin sensitivity.

http://www.fedoa.unina.it/11611/1/Di Guida_Francesca_29.pdf

 

[managing]

one thing I am seeing is that it is much more effective on an empty stomach than with food.

 

[Sativa]

Two additional components of black pepper are worth noting: Guineensine is an anandamide reuptake inhibitor (22), whereas piperine, the pungent component of black pepper, is yet another agonist at the TRPV1 receptor (23), which would presumably stimulate synthesis and release of anandamide (8).
~A Neglected Link Between the Psychoactive Effects of Dietary Ingredients and Consciousness-Altering Drugs
_

Anandamide (N-arachidonylethanolamine) is a brain lipid that binds to cannabinoid receptors with high affinity and mimics the psychoactive effects of plant-derived cannabiniod drugs
_

by C Kramar - ‎2017 - ‎Cited by 15 - ‎Related articles
1 Jan 2017 - Palmitoylethanolamide Modulates GPR55 Receptor Signaling in the Ventral Hippocampus to Regulate Mesolimbic Dopamine Activity,
_

A large body of evidence supports the anticancer activity of cannabidiol, whose putative targets further include the cannabinoid receptor 2 (CB2), serotonin 5-HT1A receptor, GPR55 and the peroxisome proliferator-activated receptor gamma. (PPAR-gamma)43 In bladder cancer, 30 μM cannabidiol was shown to lead to cell death through TRPV2-mediated Ca2+ influx, suggesting the feasibility of activating TRPV2 channels as therapeutic strategy.
...
Cannabigerol is a cannabinoid that potently blocks TRPM8 (IC50 = 0.11 ± 0.02 μM) while moderately activating TRPV1, TRPV2 and TRPA1 channels.
~Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents - Chemical Society Reviews (RSC Publishing) DOI:10.1039/C5CS00916B

 

[Sativa]

Cannabinoids made from endogenous and exogenous PUFAs
______________________________________________________​

Cannabinoids made from PUFAs

Cannabinoid receptor activation is involved in homeostatic regulation of the body. These receptors are activated by cannabinoids, that include the active constituents of Cannabis sativa, as well as endocannabinoids (eCBs). The eCBs are endogenously synthesized from the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). The consumption of omega-3 fatty acids shifts the balance towards a higher proportion of omega-3 eCBs, whose physiological functions warrants further investigation. Herein, we review the discovery of omega-3 fatty acid derived eCBs that are generated from long chain omega-3 PUFAs - docosahexaenoyl ethanolamide (DHA-EA or synaptamide), docosahexanoyl-glycerol (DHG), eicosapentaenoyl ethanolamide (EPA-EA) and eicosapentanoylglycerol (EPG). Furthermore, we outline the lesser known omega-3 eCB-like molecules that arise from the conjugation of omega-3 fatty acids with neurotransmitters serotonin and dopamine - DHA-serotonin (DHA-5HT), DHA-dopamine (DHA-DA), EPA-serotonin (EPA-5HT) and EPA-dopamine (EPA-DA).
~Emerging class of omega-3 fatty acid endocannabinoids & their derivatives - ScienceDirect

Cannabinoids made from MEAD acid aka the natural bodies endogenous omega 9 pufa

The recently discovered endogenous agonist for the cannabinoid receptor, anandamide can be formed enzymatically by the condensation of arachidonic acid with ethanolamine.
...
5Z,8Z,11Z-Eicosatrienoic acid (mead acid) has been found to substitute for arachidonic acid in the sn-2 position of phospholipids and accumulate during periods of dietary fatty acid deprivation in rats
In the present study, the chemically synthesized ethanolamide of mead acid was evaluated as a potential agonist at the two known subtypes of cannabinoid receptor: CB1 (central) and CB2 (peripheral).
This compound was equipotent to anandamide
Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CB1) and peripheral (CB2) cannabinoid receptors. - PubMed - NCBI

 

[Sativa]

Basil and oregano have the ingredient β-caryophyllene, a natural bicyclic sesquiterpene, which is an agonist of cannabinoid receptor 2 (CB2) and has been shown to be involved in anti-inflammatory actions. Eugenol, a phenylpropene and an allyl chain-substituted guaiacol is one of the active ingredients in basil and clove (Figure (Figure4).4). Other ingredients include citral that provides the citrus smell to basil, camphene in the African blue basil, and anethole in licorice and basil. Eugenol has anti-inflammatory properties by blocking the cyclooxygenase enzyme. Eugenol activates TRPV1 and TRPV3115(Table 1).

Bay leaves (Cinnamonium tamala) belong to the family Lauraceae. The active ingredients include β-caryophyllene, eugenol, and linalool, a naturally occurring terpene alcohol found in many flowers and spice plants. As discussed above, eugenol can activate TRPV1 and TRPV3 ion channels and linalool can activate TRPA1.116

Black pepper (Piper nigrum) belongs to the family Piperaceae. The active ingredients have been isolated. The main ingredient is piperine. Other alkaloids present in black pepper include chavicine and piperidine (Figure (Figure3).3). Piperine activates TRPV1.117 The pungency of pepper is due to the alkaloid piperine
...
As discussed earlier, several ingredients in Cannabis sativa can activate TRP channels.119 Cannabidiol (CBD) does not exhibit any psychotropic effects. Recently, CBD has gained attention because of its effectiveness in treating refractory epilepsies in children. CBD and other active ingredients in cannabis are considered as activators of TRPV1 (Figure (Figure4).4). CBD activates TRPV1 with EC50 of 3.2 μM as compared to activation by capsaicin (EC50 of 0.3–0.7 μM).1,119

Camphor, a terpenoid, is a transparent solid obtained from an evergreen tree Cinnamomum camphora. Another source of camphor is from dried rosemary (Rosmarinus officinalis). Camphor is an activator of TRPV1.120

~Transient Receptor Potential Channels as Targets for Phytochemicals

 

[managing]

Very interesting stuff @Sativa . Thanks for sharing.

 

[Advocate2021]

Based upon recommendation from a forum member in a thread i started for help with severe chemical hypsersensitivity 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.

 

[PeskyPeater]

@Advocate2021

Hehe, funny to read that it knocked you out. I think it's the combination of gaba effect from the increased allopregnanolone via PPar activation and and it activating the cannbinoid system too which can be sedating. It may take some time to get used too. For someone I know it had kind of a depressing effect but I guess she is not used to a calmer state of brain.

You can read more about it here: https://www.researchgate.net/public...in_Palliation_A_Qualitative_Systematic_Review

 

[TobyBjorn]

Based upon recommendation from a forum member in a thread i started for help with severe chemical hypsersensitivity 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.

Wonderful to hear!
I just took 1200mg, as I often do when I feel discomfort in my body that does not fade with a bit of stretching and movement. I love PEA, and I have been using it intermittently for a handful of years. There has been no attenuation of its benefits with chronic use. I don't find it sedating, but it does effect my consciousness in some positive, difficult-to-describe, very subtle way.