Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, and lipid modulator  PEA has been studied in in vitro and in vivo systems using exogenously added or dosed compound; there is evidence that it binds to a nuclear receptor, through which it exerts a variety of biological effects, some related to chronic inflammation and pain.
A main target of PEA is proposed to be the peroxisome proliferator-activated receptor alpha (PPAR-α). PEA also has affinity to cannabinoid-like G-coupled receptors GPR55 and GPR119. PEA cannot strictly be considered a classic endocannabinoid because it lacks affinity for the cannabinoid receptors CB1 and CB2. However, primary research supports the conclusion that the presence of PEA (or other structurally related N-acylethanolamines) enhances anandamide activity by an "entourage effect".
Some primary research reports support the conclusion that PEA levels are altered and that the endocannabinoid system (ECS) is "imbalanced" in acute and chronic inflammation. A primary research article, for instance, has reported that the deregulation of cannabinoid receptors and their endogenous ligands accompanies the development and progression of β-amyloid-induced neuroinflammation.
In some primary research studies, PEA has been shown to have anti-inflammatory, anti-nociceptive, neuroprotective, and anticonvulsant properties.