{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:07Z","timestamp":1787028547069,"version":"build-2736575974"},"reference-count":117,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), a progressive neurodegenerative disorder, manifests through dysregulation of brain function and subsequent loss of bodily control, attributed to \u03b2-amyloid plaque deposition and TAU protein hyperphosphorylation and aggregation, leading to neuronal death. Concurrently, similar cannabinoids to the ones derived from Cannabis sativa are present in the endocannabinoid system, acting through receptors CB1R and CB2R and other related receptors such as Trpv-1 and GPR-55, and are being extensively investigated for AD therapy. Given the limited efficacy and adverse effects of current available treatments, alternative approaches are crucial. Therefore, this review aims to identify effective natural and synthetic cannabinoids and elucidate their beneficial actions for AD treatment. PubMed and Scopus databases were queried (2014\u20132024) using keywords such as \u201cAlzheimer\u2019s disease\u201d and \u201ccannabinoids\u201d. The majority of natural (\u03949-THC, CBD, AEA, etc.) and synthetic (JWH-133, WIN55,212-2, CP55-940, etc.) cannabinoids included showed promise in improving memory, cognition, and behavioral symptoms, potentially via pathways involving antioxidant effects of selective CB1R agonists (such as the BDNF\/TrkB\/Akt pathway) and immunomodulatory effects of selective CB2R agonists (TLR4\/NF-\u03baB p65 pathway). Combining anticholinesterase properties with a cannabinoid moiety may enhance therapeutic responses, addressing cholinergic deficits of AD brains. Thus, the positive outcomes of the vast majority of studies discussed support further advancing cannabinoids in clinical trials for AD treatment.<\/jats:p>","DOI":"10.3390\/ijms25168630","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T15:04:24Z","timestamp":1723129464000},"page":"8630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Comprehensive Exploration of the Multifaceted Neuroprotective Role of Cannabinoids in Alzheimer\u2019s Disease across a Decade of Research"],"prefix":"10.3390","volume":"25","author":[{"given":"Petros","family":"Tyrakis","sequence":"first","affiliation":[{"name":"Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Agridi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4176-8425","authenticated-orcid":false,"given":"Malamati","family":"Kourti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). 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