In a 2015 article titled:
Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals
authors provided explicitly evidence for the treatment of various braindisorders by PEA.
5 scientists demonstrated that palmitoylethanolamide has a specific neuroprotective effect in their model. The authors start with an emphasis on the safety and the efficiacy of PEA:
Palmitoylethanolamide (PEA) is an endogenous lipid belonging to the family of fatty acid ethanolamides . PEA has received considerable attention because of its low toxicity and many pharmacological activities such as anti-inflammatory, analgesic, and immunomodulatory effects. PEA is abundant in the central nervous system (CNS) and exerts neuroprotective effects. Moreover, PEA administration has been reported to reduce brain damage and improve behavioral dysfunctions in several experimental models of CNS injury and disease, including epilepsy, cerebral ischemia, stroke, Alzheimer’s disease, and Parkinson’s disease. These findings suggest that PEA acts as an endogenous protective factor of the brain; however, the precise mechanisms involved in this role are unclear.
In an elaborate model the authors assessed the effects and possible mechanism of PEA on glutamate release from rat cerebrocortical nerve terminals (synaptosomes). The model was a preparation by which presynaptic effects could be directly investigated, excluding extrasynaptic and polysynaptic events and the non-neuronal release of glutamate. The authors demonstrated that PEA could inhibit the Ca2+-dependent exocytosis of glutamate evoked by a certain toxin with an IC50 value in the micromolar range. As no other studies have investigated the effect of PEA on endogenous glutamate release, this is the first report to document the mechanism by which PEA inhibits glutamate release at the presynaptic level. It brings further context to the neuroprotective properties of PEA.
The conclusion was:
Our data show that PEA exerts an inhibitory effect on the evoked glutamate release from cerebrocortical nerve terminals by a mechanism that involves the suppressing of Cav2.1 (P/Q-type) channels and PKA activity. Furthermore, this release inhibition likely depends, at least in part, on the activation of cannabinoid CB1 receptors. Because the excitotoxicity caused by excessive glutamate release is a critical element in the pathogenesis of acute and chronic brain disorders, the ability of PEA to depress glutamate release may be one of the mechanisms underlying neuroprotection. This investigation extends our knowledge on the mode of PEA action in the brain and provides a rationale for using PEA to treat brain disorders.
Lin TY, Lu CW, Wu CC, Huang SK, Wang SJ. Palmitoylethanolamide inhibits glutamate release in rat cerebrocortical nerve terminals. Int J Mol Sci. 2015 Mar 11;16(3):5555-71. doi: 10.3390/ijms16035555.