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Comment · Tue, April 14, 2020 · Natrium Health & Nootropics Depot

How safe is palmitoylethanolamide(PEA)?

Original post in this thread

JimmySteve3 · 8 points

I recently ordered some PEA and it just arrived in the mail today. I was doing a bit of extra research and came across a Reddit thread that had a user asking about whether there was any risk with PEA because it is a COX2 inhibitor. They were asking about whether it could cause a vascular event because of this. Is it safe for me to take PEA?

This is the link to the thread: https://amp.reddit.com/r/Nootropics/comments/6ayw8r/palmitoylethanolamide_pea_as_a_cox2_inhibitor/

What they were answering

Direct reply to the original post — see the thread post above.

u/MisterYouAreSoDumb · Natrium Health & Nootropics Depot

Palmitoylethanolamide is an endogenous fatty acid amide. That means it's in your body right now. Some people just make less of it, and your levels fall as you get older. So supplementation can help bring those levels back up. It's also found in foods, too. It's very safe. Most people don't understand what it is, and miss the point altogether. If you are someone that has good natural levels of PEA in your body, you likely will not feel anything. However, people that do have naturally lower levels feel the effects very strongly. This is why you see polarizing views on it.

Now regarding your question about COX-2 specifically, it is a modulator of COX-2, not a competitive inhibitor. It binds to the endocannabinoid receptors GPR55 and GPR119. That's how it regulates the expression of cyclooxygenase-2 (COX-2) as well as inducible nitric oxide synthase (iNOS). It is also a PPAR-α agonist, which regulates IkB-alpha degradation and p65 NF-kappaB nuclear translocation. Its PPAR-α affinities are actually how it reduces neuroinflammation. On top of its direct binding affinities, it leads to increased binding of anandamide to the CB1 and CB2 receptors, which is your body's primary endocannabinoid. It's a really cool compound!

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