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Endocannabinoids, mainly anandamide and 2-arachidonoylglycerol, are natural ligands of the cannabinoid receptors CB1 and CB2, which are widely distributed throughout the central nervous system and peripheral tissues. Their biosynthesis, degradation, and interaction with other signaling pathways play crucial roles in both health and disease. This article provides a comprehensive overview of the physiological and pathological roles of endocannabinoids, discusses their potential as therapeutic targets, and highlights recent advances in endocannabinoid-based treatments.<\/jats:p>","DOI":"10.3390\/jcm14082851","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T20:38:26Z","timestamp":1745267906000},"page":"2851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["The Role of Endocannabinoids in Physiological Processes and Disease Pathology: A Comprehensive Review"],"prefix":"10.3390","volume":"14","author":[{"given":"Paulina","family":"Simankowicz","sequence":"first","affiliation":[{"name":"Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0801-7582","authenticated-orcid":false,"given":"Joanna","family":"St\u0119pniewska","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70009","DOI":"10.1002\/prp2.70009","article-title":"The endocannabinoid system in appetite regulation and treatment of obesity","volume":"12","author":"Kurtov","year":"2024","journal-title":"Pharmacol. 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