title: Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice.
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.
authors.affiliation: Institut de Neuropatologia, Servei d'Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Aso
authors.affiliation: Departament d'Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain Statistics and Bioinformatics Unit, Institut de Recerca de l'Hospital Universitari de Vall d'Hebron, Barcelona, Spain.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Sánchez-Pla
authors.affiliation: Departament d'Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Vegas-Lozano
authors.affiliation: Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.affiliation: Institut de Neuropatologia, Servei d'Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005911:Gliosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007858:Learning / Q000187:drug effects; D064086:Medical Marijuana / Q000494:pharmacology* / Q000627:therapeutic use; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D064086:Medical Marijuana
keywords: Alzheimer's disease; animal model; cannabidiol; tetrahydrocannabinol; therapy