The existence of acylethanolamides (AEs) in the mammalian brain has been known for decades. Among AEs, palmitoylethanolamide (PEA) is abundant in the central nervous system (CNS) and conspicuously produced by neurons and glial cells. Antihyperalgesic and neuroprotective properties of PEA have been mainly related to the reduction of neuronal firing and to control of inflammation. Growing evidence suggests that PEA may be neuroprotective during CNS neurodegenerative diseases.

Tool for disease management

Advances in the understanding of the physiology and pharmacology of PEA have potentiated its interest as the useful biological tool for disease management. Several rapid non-genomic and delayed genomic mechanisms of action have been identified for PEA as peroxisome proliferator-activated receptor (PPAR)-α dependent. First, an early molecular control, through Ca(+2)-activated intermediate- and/or big-conductance K(+) channels opening, drives to rapid neuronal hyperpolarization. This is reinforced by the increase of the inward Cl(-) currents due to the modulation of the gamma-aminobutyric acid A receptor and by the desensitization of the transient receptor potential channel type V1.

Moreover, the gene transcription-mediated mechanism sustains the long-term anti-inflammatory effects, by reducing pro-inflammatory enzyme expression and increasing neurosteroid synthesis. Overall, the integration of these different modes of action allows PEA to exert an immediate and prolonged efficacious control in neuron signaling either on inflammatory process or neuronal excitability, maintaining cellular homeostasis. In this review, we will discuss the effect of PEA on metabolism, behavior, inflammation and pain perception, related to the control of central functions and the emerging evidence demonstrating its therapeutic efficacy in several neurodegenerative diseases.

Palmitoylethanolamide for threatment of glaucoma

Palmitoylethanolamide is especially in Italy and the USA at the moment hot for the treatment of glaucoma. We prefer treatment either with the Italian PEA tablets, based on PEA-um or PEA-m, or by administrating the Dutch PEA capsules containing PEA-opt. Dutch capsules do not contain any chemical excipients and are 100% pure in vegetarian capsules.

For pain relief and for inhibiting inflammation, most patients choose:

  • PEA capsules produced in the Netherlands by Russell
  • PEA tablets produced in Italy by Epitech

Only for these the Dutch and the Italian formulations long-term safety and efficacy data gathered under the supervision of MDs are available. And only for these formulations (PEA-um, PEA-m and PEA-opt) there are currently data available proving that after intake PEA levels in the body significantly rise. Such data do not exist for me-too PEA formulations.


Palmitoylethanolamide in CNS health and disease.

Mattace Raso G, Russo R, Calignano A, Meli R.

Pharmacol Res. 2014 Aug;86:32-41. doi: 10.1016/j.phrs.2014.05.006. Epub 2014 May 17.