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Recently, the endocannabinoid system has attracted growing attention from the scientific community for its involvement in homeostatic and pathological processes as they pertains to human physiology. Among the constituents of the endocannabinoid system, the molecule palmitoyl ethanolamide has particularly been studied for its ability to reduce several inflammatory processes involving the central nervous system. Here, we reviewed published literature and summarized the main targets of the palmitoyl ethanolamide, along with its unique possible mechanisms for restoring correct functioning of the central nervous system. Moreover, we have highlighted a less-known characteristic of palmitoyl ethanolamide, namely its ability to modulate the function of the neuromuscular junction by binding to acetylcholine receptors in different experimental conditions. Indeed, there are several studies that have highlighted how ultra-micronized palmitoyl ethanolamide is an interesting nutraceutical support for the treatment of pathological neuromuscular conditions, specifically when the normal activity of the acetylcholine receptor is altered. Although further multicentric clinical trials are needed to confirm the efficacy of ultra-micronized palmitoyl ethanolamide in improving symptoms of neuromuscular diseases, all the literature reviewed here strongly supports the ability of this endocannabinoid-like molecule to modulate the acetylcholine receptors thus resulting as a valid support for the treatment of human neuromuscular diseases.
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http://dx.doi.org/10.3390/biom12060758 | DOI Listing |
Eur J Neurol
August 2025
Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy.
Background: Peripheral neuropathies encompass a diverse group of disorders involving peripheral nerve damage, often leading to pain, sensory disturbances, and motor impairments. The etiology is multifactorial, with trauma as a key contributor. The treatment of peripheral neuropathies includes medications targeting the nociceptive component, whereas the neuropathic component is managed with agents such as gabapentinoids or antidepressants, though their prolonged use is limited by significant side effects.
View Article and Find Full Text PDFIndian J Pharmacol
July 2025
Consulting Pharmacologist, Tejhana Consulting LLP, Bengaluru, Karnataka, India.
Background: Palmitoylethanolamide (PEA) is an endogenous fatty acid amide signaling molecule that may indirectly modulate the endocannabinoid system. It has poor water solubility and, therefore, is not readily absorbed in the human body. Various formulation techniques have been developed to enhance the rate of dissolution of PEA and minimize the variability of drug absorption when administered orally.
View Article and Find Full Text PDFSci Rep
July 2025
Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Pozzuoli (Napoli), 80078, Italy.
N-palmitoyl-D-glucosamine (PGA) belongs to the class of molecules known as Autacoid Local Injury Antagonism (ALIA)-amides, whose parent compound is N-palmitoyl-ethanolamine (PEA) an endocannabinoid-like mediator belonging to the expanded endocannabinoid system (the endocannabinoidome). The mechanism of action of ALIA-amides is mainly targeted at the down-regulation of the hyperactivity of peripheral mast cells and non-neuronal cells of the central nervous system. This study aimed to investigate if PGA is able to produce the typical "entourage" effect of PEA, consisting of increasing the endogenous levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and to also elevate endogenous PEA levels.
View Article and Find Full Text PDFNutrients
June 2025
Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), 13100 Vercelli, Italy.
The blood-brain barrier (BBB) plays a critical role in protecting the central nervous system (CNS) but also limits drug delivery. Insufficient knowledge of how the CNS promotes the onset and maintenance of peripheral neuropathic pain limits therapeutic methods for the treatment of persistent neuropathic pain. Thus, this study aimed to evaluate the ability of a novel combination of Palmitoylethanolamide (PEA) and L.
View Article and Find Full Text PDFWorld J Biol Psychiatry
June 2025
Faculty of Medicine, Department of Medical Pharmacology, Trakya University, Edirne, Turkey.
Background: Although the brain is not the only source of circulating endocannabinoids and their levels can be affected by many factors, it is underlined that serum endocannabinoid levels can be used as a biomarker in psychiatric disorders. In this study, we aimed to examine whether serum endocannabinoid and N-acylethanolamine concentrations reflect their brain levels.
Methods: In the present study acute immobilisation (AIS) and post-traumatic stress (PTSD) models were applied to Wistar albino male rats.