Get to Know PEA and Its History

What is PEA?

Palmitoylethanolamide (PEA) is a naturally occurring lipid discovered more than 50 years ago, when it was first isolated from soy lecithin, egg yolk, and peanut meal.1 It is a long-chain N-acylethanolamine (NAE) and analog of the endocannabinoid anandamide (AEA) that is present in animals and plants.2-4

History of PEA

In 1954, published findings asserted that extracts from egg yolk and peanut oil had anti-inflammatory activity.5 The component in those extracts was identified in 1957 and named palmitoylethanolamide.5 In the years between 1954 and 1979, researchers found that in addition to its anti-inflammatory properties, PEA also plays a role in immune system activity.5

Because of a lack of clarity around PEA’s mechanism of action, research ground to a halt in the 1980s, then picked up steam again in the early 1990s when PEA was identified as a mast cell modulator.5

Sources of PEA

PEA is present in low levels in the human body.6 The body synthesizes PEA from palmitic acid, the most common fatty acid in animals and a component of many foodstuffs such as soy lecithin, soybean, peanuts, among others.4

PEA’s mechanisms of action

Investigations have determined that PEA’s pharmacological effects are achieved through several different mechanisms of action. Several studies have found that PEA directly activates two different nonclassical cannabinoid receptors.7

Effect of PEA on the endocannabinoid system

Initially, PEA was believed to be an agonist of the type 2 cannabinoid receptor (CB2), which is present throughout the immune system.2,8 But it has since been discovered that PEA cannot bind to the known cannabinoid receptors.2

However, it is possible that PEA indirectly activates CB2, as well as the type 1 cannabinoid receptor (CB1) found in the central nervous system, due to the endocannabinoid system’s “entourage effect.”3,7-9 The entourage effect was first proposed as a theory to explain why single components of botanical substances such as cannabis were not as effective as the entire botanical.9 According to the entourage effect theory, certain inactive metabolites and closely related molecules significantly increase the activity of some cannabinoids on the body’s endocannabinoid system (ECS),9 which controls and regulates many physiological functions in our bodies.10

One way in which PEA can indirectly activate CB1 and CB2 receptors is by inhibiting the expression of fatty acid amide hydrolase (FAAH), an enzyme that degrades the CB1 agonist AEA.3,7 The transient receptor potential vanilloid receptor type 1 (TRPV1) channels, which are also endocannabinoid targets, can also be indirectly activated by PEA.7 From these activities, it can be surmised that PEA needs synergistic actions among several mechanisms for it to be able to produce its effects.7


As mentioned earlier, the beneficial properties of PEA have been recognized since the 1950s. Clinical trials conducted since 1970 have demonstrated PEA’s immune-modulating capabilities.4

PEA is involved in a number of metabolic functions in the body, as well as in maintaining a balance of factors that keep cells healthy.4


  1. Beggiato S et al. Front Pharmacol. 2019;10:821.
  2. PubChem, U.S. National Library of Medicine, National Center for Biotechnology Information. Accessed  September 20, 2019
  3. Passavanti MB et al. Syst Rev. 2019;8(9).
  4. Hesselink JM et al. Int J Inflamm. 2019;2013(9).
  5. Hesselink JMK. J Pain Res. 2013;6:625–634.
  6. Hansen HS. CNS Neurol Disord. 2013;12(1):17–25.
  7. Petrosino S et al. Br J Pharmacol. 2017;174(11):1349–1365.
  8. Reggio P. Curr Med Chem. 2010;17(14):1468–1486.
  9. Russo E. Front Plant Sci. 2018;9:1969.
  10. Aizpurua-Olaizola O et al. Drug Discov Today. 2017;22(1):105-110.

Submitted by the Metagenics Marketing Team

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