Feature Summary

Palmitoylethanolamide (PEA) is an endogenously produced lipid that mediates the resolution of neuroinflammation and clinically reduces pain from a variety of sources. PEA is a type of fatty acid ethanolamine produced in microglia and mast cells, where it downregulates the activation of both cell types; levels of PEA are increased in brain areas involved in nociception, and appear to modulate protective responses to both inflammation and pain. Its effects are mediated via direct activation of PPAR-a and GPR55 receptors, and potentially by indirect activation of CB1 and CB2 receptors and the TRPV1 channel (i.e., the capsaicin receptor).

In clinical trials, PEA has been shown to reduce pain levels from a variety of chronic conditions (of at least 6 months duration) where pain was not controlled by standard therapies, demonstrating effectiveness both alone and when combined with standard treatments. PEA has been shown to be efficacious for pain resulting from nerve compression syndromes, including sciatica and carpal tunnel syndrome. Randomized trials have also shown benefit for pain control for specific conditions, including TMJ, as well as for depressive symptoms in major depressive disorder when used in conjunction with antidepressants. In addition, PEA has been shown to improve endothelial function and reduce intraocular pressure among patients with ocular hypertension.