Written by Whittney Wacker, RN, BSN
Palmitoylethanolamide (PEA) is a naturally occurring fatty acid with many uses. Cannabis clinicians, along with other healthcare providers of today, are touting it as an entourage effect influencing molecule, available over the counter and found in many foods. According to Cannakeys (n.d.) PEA was identified in 1957 (Cannakeys, n.d.). Di Marzo (2018) reports in his paper New approaches and challenges to targeting the endocannabinoid system, PEA impacts homeostasis through the modulation of TRPv1, GPR55, GPR119 and PPAR alpha receptors, this is further confirmed in the Clayton, et al (2021) paper. Much like other related endogenous fatty acid derivatives, like OEA and SEA, PEA does not directly interact with the CB1 or CB2 receptors. In the presence of PEA mammalian physiologic functions like inflammation, immune functions, pain, GI/GU distress, behaviors associated with autism, sleep, oxidative stress, amongst others, improves (Cannakeys n.d.). PEA associates itself with other endocannabinoids, like AEA, at the specific sites of CB1, CB2, Trpv1, GPR55 and GRP118, influencing (not binding) and enhancing activity towards equilibrium, thus furthering the argument for PEA adding to the “entourage effect” (Foster, 2021). PEA is “synthesized on demand in the lipid bilayer (Clayton, 2021).” Petrosino and Di Marzo (2017) report PEA is degraded by fatty acid amide hydrolase (FAAH) into palmitic acid and ethanolamine (Petrosino and Di Marzo, 2017). In the absence of blood tests that directly measure PEA’s activity, it could be detected through AEA activity via enzyme-linked immunosorbent assay (ELISA) tests (Sahinovic, et al 2022). If an AEA deficiency is detected through ELISA test, PEA could be ingested either by micronized (smaller particle size for improved absorbing action) capsules on the market today or through dietary means by eating peanuts, corn, soy, egg yolks and certain milks (Cannakeys, n.d.). Over the counter PEA is well-tolerated and devoid of side effects as Clayton et al (2021) report.
Cannakeys. (n.d.), retrieved from https://cannakeys.com/palmitoylethanolamide-pea-cannabinoid-research/
Clayton, P., Hill, M., Bogoda, N., Subah, S., & Venkatesh, R. (2021, May 18). Palmitoylethanolamide: A natural compound for health management. International journal of molecular sciences. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157570/
Di Marzo, V. (2018, September 17). New approaches and challenges to targeting the endocannabinoid system. Nature reviews. Drug discovery. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30116049/
Foster, D. A. (2021). Chapter 2: The Human Endocannabinoid System (ECS): Physiology. In C.S. Clark (Ed.), Cannabis: A handbook for nurses (pp. 44–114). Wolters Kluwer.
Petrosino, S., & Di Marzo, V. (2017, June). The pharmacology of Palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. British journal of pharmacology. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429331/
Sahinovic, I., Mandic, S., Mihic, D., Duvnjak, M., Loinjak, D., Sabadi, D., Majic, Z., Peric, L., & Seric, V. (2022, June 1). Endocannabinoids, anandamide and 2-arachidonoylglycerol, as prognostic markers of sepsis outcomes and compliations. LibertPub. Retrieved from https://www.liebertpub.com/doi/10.1089/can.2022.0046
Journal Articles on PEA listed below:
- Palmitoylethanolamide: a natural compound for health management. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157570/
- PubChem compound classification: https://pubchem.ncbi.nlm.nih.gov/compound/Palmitoylethanolamide
- Chronic Oral Palmitoylethanolamide administration rescues cognitive deficit and reduces neuro-inflammation, oxidative stress and Glutamate levels in a transgenic murine model of Alzheimer's Disease. https://alzped.nia.nih.gov/chronic-oral
- New approaches and challenges to targeting the endocannabinoid system. https://pubmed.ncbi.nlm.nih.gov/30116049/
- The Pharmacology of Palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429331/
- Efficacy of Palmitoylethanolamide for Pain: A meta-analysis. https://pubmed.ncbi.nlm.nih.gov/28727699/
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