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Unfortunately, these diseases currently have no cure; only symptomatic treatment is available. Therefore, there is still a growing interest in using cannabinoids to treat neurodegenerative diseases. This systematic review examines the interrelationship between cannabinoids, the blood\u2013brain barrier, and neurodegeneration, and their mutual effects. The objective of this review is to provide an overview of the endocannabinoid system at the neurovascular interface, the alterations and dysregulation of the ECS in neurodegenerative diseases, the interactions of phytocannabinoids with the blood\u2013brain barrier, and their therapeutic potential in the context of neurodegeneration. The findings may facilitate the targeted application of cannabinoids to address multiple aspects of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/biom16020225","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:00:47Z","timestamp":1770033647000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cannabinoids, the Blood\u2013Brain Barrier, and Neurodegeneration: Mechanisms, Dysregulation, and Therapeutic Perspectives"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7551-5488","authenticated-orcid":false,"given":"Shimon","family":"Ben-Shabat","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4962-4938","authenticated-orcid":false,"given":"Ludmila","family":"Yarmolinsky","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitzan","family":"Sharon","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taima","family":"Zeadnaa-Aldda","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3323-958X","authenticated-orcid":false,"given":"Shir","family":"Dayan","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1695-6544","authenticated-orcid":false,"given":"Boris","family":"Khalfin","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0797-8816","authenticated-orcid":false,"given":"Sigal","family":"Fleisher-Berkovich","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s11172-015-1008-1","article-title":"Cannabinoids: Structures, Effects, and Classification","volume":"64","author":"Shevyrin","year":"2015","journal-title":"Russ. 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