How Does Palmitoylethanolamide (PEA) Work?

You can learn about the efficacy and complete safety of the substance by clicking this link, but here you will find out about the mechanism that lies behind the benefits.

The cells in the body have numerous different receptors on their surfaces. These receptors are there so that various different molecules can bind to them. When this binding occurs, it triggers a biological process inside the cell. The nature of the process greatly depends on the kind of the receptor and the kind of the molecule that binds to its.

Palmitoylethanolamide affects several different receptors which exert an incredibly wide array of benefits for the whole body. It binds directly to some receptors and it affects some others through other endogenous molecules, such as anandamide and oleoylethanolamide.

Here is a list of some receptors that palmitoylethanolamide affects and just an introduction to what their individual benefits are.

  1. PPAR-alpha

This receptor is considered the primary target of PEA and also oleoylethanolamide. It is a part of the process of ketogenesis and it spreads through brown adipose tissue, heart, kidneys, lungs, adrenal gland, liver, intestines and skeletal muscle. It also regulates the lipid metabolism. The list doesn’t end there and just a quick view of its gene ontology reveals that PPAR-alpha is extremely versatile and beneficial.

  1. CB1

CB1 is the first cannabinoid receptor discovered in the body and it is most prominent in the central nervous system where it, among other things, deals with pain-related issues. It is also present in kidneys, liver and lungs. It is not a direct target of PEA, but studies have shown that taking PEA greatly increases its activity. The most probable answer is that PEA affects CB1 through anandamide, which plays a major role in the body and which is also quickly and easily degraded by the same enzyme that degrades PEA. This means that having more PEA in the body greatly increases the efficacy of both anandamide and PEA and it explains the positive effects on CB1. Whatever the reason, the positive effects of PEA through CB1 are well documented.

  1. CB2

CB2 is the reason why PEA is so important for the immune system. It is found in hematopoietic cells, B cells and macrophages. Just some of the effects of these cells include eliminating microbes, cellular debris and cancer cells (done by macrophages), helping create antibodies (by B cells) and increasing the number of blood cell (by hematopoietic cells).

  1. GPR55

GPR55 is often called novel cannabinoid receptor and its effects on the endocannabinoid system are vast. It is found in ileum, cerebellum, bone cells and jejunum.

  1. GPR119

GPR119 is also a recently discovered receptor which is found in pancreas where it controls the secretion of incretin and insulin and gastrointestinal tract where it regulates the feeling of hunger.

However, this is not all. More recent studies show that not all of the effects of PEA fall within these receptors. For example, it is becoming more and more clear that PEA also affects TRPV1 and that there are bound to be more receptors which will be discovered as the scientists break into more secrets within and outside the endocannabinoid system.

Speaking of pain and inflammation in particular, aside from the mentioned benefits, it is worth noting that PEA has been found to control iNOS and COX-2 expression and the influx of neutrophils. This is something that is also done by some of the most infamous NSAIDs and opioids. The difference is that PEA does it in a natural and completely safe way.