{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:07:26Z","timestamp":1787062046574,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer\u2019s Australia Dementia Research"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["#1102012"],"award-info":[{"award-number":["#1102012"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["#1141789"],"award-info":[{"award-number":["#1141789"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["#1095215"],"award-info":[{"award-number":["#1095215"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Alzheimer\u2019s disease (AD) is a neurodegenerative disease for which there are no highly effective treatments, which highlights the need for novel therapeutics. Cannabidiol (CBD) has demonstrated antioxidant, anti-inflammatory and neuroprotective properties. Chronic CBD treatment (20 mg\/kg and 50 mg\/kg) reverses social recognition memory deficits of APPSwe\/PS1\u2206E9 (APP\/PS1) transgenic mice; however, it does not produce effects on AD-relevant brain pathology. Methods: Here, we investigated whether chronic high-dose CBD treatment (i.e., 100 mg\/kg intraperitoneally) in early symptomatic 7.5-month-old APP\/PS1 males would reverse cognitive deficits while also influencing neuropathological markers relevant to AD. Mice were assessed for anxiety, recognition memory, and social and aggressive behaviours before carrying out neuropathological analyses of collected brain tissue. Results: Vehicle-treated APP\/PS1 transgenic males demonstrated reduced aggressive behaviour and increased socio-positive behaviour. A moderate deficit in social recognition memory was restored by CBD. APP\/PS1 mice also exhibited elevated cortical proBDNF levels under vehicle treatment, and hippocampal levels of TNF-\u03b1 and IL-1\u03b2 were reduced in all APP\/PS1 mice. AD transgenic mice exhibited no changes in soluble or insoluble A\u03b242 levels or PPAR\u03b3 isoforms. Conclusions: This study found that high-dose CBD restored a moderate social recognition memory deficit. However, CBD did not have marked effects on AD-relevant neuropathological markers assessed, most likely because the AD transgenic mice were evaluated at a disease stage too early to detect significant pathological changes. Thus, the underlying mechanisms for CBD\u2019s effect on social recognition memory require further investigation.<\/jats:p>","DOI":"10.3390\/ph19030374","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:41:02Z","timestamp":1772188862000},"page":"374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Chronic 100 mg\/kg Cannabidiol Treatment in Male Double Transgenic APPSwe\/PS1\u2206E9 Mice"],"prefix":"10.3390","volume":"19","author":[{"given":"Georgia","family":"Watt","sequence":"first","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Olaya","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia, Randwick, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Muench","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Garner","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9904-8482","authenticated-orcid":false,"given":"Tim","family":"Karl","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2018). 2018 alzheimer\u2019s disease facts and figures. 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