{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:19Z","timestamp":1792800019878,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>\n                    Cannabinoids have emerged as potential modulators of pathological processes in Alzheimer\u2019s disease (AD), including neuroinflammation, synaptic dysfunction, and protein aggregation. Cannabidiol (CBD) and \u03949-tetrahydrocannabinol (THC), the main phytocannabinoids from\n                    <jats:italic>Cannabis sativa<\/jats:italic>\n                    , interact with the endocannabinoid system and may influence neuronal and glial signaling pathways relevant to AD pathology. This mini review summarizes evidence from transgenic animal models and clinical studies evaluating CBD, THC, and their combination in AD. Preclinical studies show that CBD and THC reduce\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -amyloid accumulation, attenuate tau phosphorylation, and regulate neuroinflammatory responses, often associated with improvements in learning and memory. Cognitive outcomes appear to depend on cannabinoid composition, with CBD or THC administered individually showing more consistent effects, while combined CBD\u202f+\u202fTHC effects appear dose- and ratio-dependent. Clinical evidence in AD patients remains limited and primarily reports improvements in neuropsychiatric symptoms, such as reductions in agitation, nighttime activity, and behavioral disturbances, whereas cognitive improvements are modest. Cannabinoid-based treatments are generally well tolerated, with mild sedation, somnolence, or disorientation as the most reported adverse effects. Overall, current data support the biological plausibility of cannabinoids as modulators of neuroinflammatory and synaptic processes in AD. However, heterogeneity in formulations, dosing, and study design limits firm conclusions. Future research should focus on dose optimization, biomarker-guided clinical trials, and long-term safety assessments to better define their therapeutic potential in AD.\n                  <\/jats:p>","DOI":"10.3389\/fnbeh.2026.1833021","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:46:04Z","timestamp":1778647564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cannabinoids in Alzheimer\u2019s disease: animal\u2013human evidence and clinical pharmacology challenges"],"prefix":"10.3389","volume":"20","author":[{"given":"Maria","family":"Komedera","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology, Polish Academy of Sciences","place":["Warszawa, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Wojda","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology, Polish Academy of Sciences","place":["Warszawa, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kiryk","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology, Polish Academy of Sciences","place":["Warszawa, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"afaf149","DOI":"10.1093\/ageing\/afaf149","article-title":"Sativex (nabiximols) for the treatment of Agitation & Aggression in Alzheimer\u2019s dementia in UK nursing homes: a randomised, double-blind, placebo-controlled feasibility trial","volume":"54","author":"Albertyn","year":"2025","journal-title":"Age Ageing"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1089\/can.2023.0101","article-title":"Effects of chronic, low-dose cannabinoids, cannabidiol, delta-9-tetrahydrocannabinol and a combination of both, on amyloid pathology in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"9","author":"Arnanz","year":"2024","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"174101","DOI":"10.1016\/j.pbb.2025.174101","article-title":"Combination treatment with medium dose THC and CBD had no therapeutic effect in a transgenic mouse model for Alzheimer\u2019s disease but affected other domains including anxiety-related behaviours and object recognition memory","volume":"257","author":"Aumer","year":"2025","journal-title":"Pharmacol. 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