{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:12:55Z","timestamp":1785445975281,"version":"3.56.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Postdoctoral Fellowship Program of CPSF","award":["GZC20233185"],"award-info":[{"award-number":["GZC20233185"]}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation of China","doi-asserted-by":"crossref","award":["2023JJ40948"],"award-info":[{"award-number":["2023JJ40948"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Youth Fund of Hunan Provincial Natural Science Foundation","award":["2025JJ60696"],"award-info":[{"award-number":["2025JJ60696"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease is a progressive neurodegenerative disorder marked by amyloid-\u03b2 (A\u03b2) plaque deposition and neurofibrillary tangles composed of hyperphosphorylated tau. Dysregulation of glycogen synthase kinase-3\u03b2 (GSK3\u03b2) promotes tau hyperphosphorylation and amplifies A\u03b2-induced neurotoxicity, driving pathogenesis. Despite extensive research, current therapies targeting these core mechanisms remain largely ineffective at halting disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Based on prior clinical and preclinical evidence, we hypothesize that cannabidiol (CBD), a non-psychoactive phytocannabinoid, may exert multitarget therapeutic effects in AD by modulating A\u03b2 aggregation, tau hyperphosphorylation, and GSK3\u03b2 activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated CBD's interactions with A\u03b2-42\/40, tau, and GSK3\u03b2 using molecular docking, molecular dynamics simulations and ADMET predictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results show that CBD binds to A\u03b2 with binding free energies of \u22127.81\u2005kcal\/mol, \u22127.46\u2005kcal\/mol, and \u22127.25\u2005kcal\/mol, disrupting aggregation by interacting with key residues (HIS6, HIS13, HIS14, GLU14, GLU22, ASP15, and ASP23). MD simulations confirm that CBD destabilizes A\u03b2's \u03b2-sheet structure, preventing fibril formation. CBD binds tau with binding free energies of \u22129.91\u2005kcal\/mol, \u22129.70\u2005kcal\/mol, and \u22129.66\u2005kcal\/mol, disrupting tau aggregation and preventing neurofibrillary tangle formation. MD simulations show that CBD induces structural changes in tau, reducing \u03b2-sheet packing and inhibiting tau-tau interactions. CBD also binds to GSK3\u03b2 with binding energies of \u22128.94\u2005kcal\/mol, \u22128.51\u2005kcal\/mol, and \u22128.41\u2005kcal\/mol, competing with ATP to inhibit its kinase activity and reduce tau phosphorylation. ADMET analysis indicates CBD's favorable oral bioavailability and low toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings support CBD as a promising multitarget therapeutic for AD, warranting further preclinical and clinical investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251386440","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:22:18Z","timestamp":1760721738000},"page":"1287-1301","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring multitarget molecular mechanisms of cannabidiol in Alzheimer's disease treatment using molecular simulations and modeling"],"prefix":"10.1177","volume":"108","author":[{"given":"Xiangyun","family":"Bi","sequence":"first","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China"},{"name":"Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China"},{"name":"Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 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