Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice

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• dc.contributor.author Aso Pérez, Esterca
• dc.contributor.author Sánchez Pla, Alexandreca
• dc.contributor.author Vegas Lozano, Estebanca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Ferrer, Isidreca
• dc.date.accessioned 2015-03-30T07:21:06Z
• dc.date.available 2015-03-30T07:21:06Z
• dc.date.issued 2015ca
• dc.description.abstract Several recent findings suggest that targeting the endogenous cannabinoid system can be considered as a potential therapeutic approach to treat Alzheimer's disease (AD). The present study supports this hypothesis demonstrating that delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD) botanical extracts, as well as the combination of both natural cannabinoids, which are the components of an already approved cannabis-based medicine, preserved memory in AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Moreover, THC + CBD reduced learning impairment in AβPP/PS1 mice. A significant decrease in soluble Aβ42 peptide levels and a change in plaques composition were also observed in THC + CBD-treated AβPP/PS1 mice, suggesting a cannabinoid-induced reduction in the harmful effect of the most toxic form of the Aβ peptide. Among the mechanisms related with these positive cognitive effects, the anti-inflammatory properties of cannabinoids may also play a relevant role. Here we observed reduced astrogliosis, microgliosis, and inflammatory-related molecules in treated AβPP/PS1 mice, which were more marked after treatment with THC + CBD than with either THC or CBD. Moreover, other cannabinoid-induced effects were uncovered by a genome-wide gene expression study. Thus, we have identified the redox protein thioredoxin 2 and the signaling protein Wnt16 as significant substrates for the THC + CBD-induced effects in our AD model. In summary, the present findings show that the combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD.
• dc.description.sponsorship This study was supported by grants from the Agrupació Mútua Foundation (XVII Award in the Elderly Field, to IF), Mutua Madrileña Foundation (IF), and BESAD-P project, CIBERNED, Instituto Carlos III (IF).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Aso E, Sánchez-Pla A, Vegas-Lozano E, Maldonado R, Ferrer I. Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice. J Alzheimers Dis. 2015;43(3):977-91. DOI: 10.3233/JAD-141014ca
• dc.identifier.doi http://dx.doi.org/10.3233/JAD-141014
• dc.identifier.issn 1387-2877ca
• dc.identifier.uri http://hdl.handle.net/10230/23305
• dc.language.iso engca
• dc.publisher IOS Pressca
• dc.relation.ispartof Journal of Alzheimer's Disease. 2015;43(3):977-91
• dc.rights © IOS Press. All rights reservedca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Cannabis
• dc.subject.other Medicina
• dc.subject.other Alzheimer, Malaltia d'
• dc.title Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 miceca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca