CBD research on - Stress

2017: The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system

hese findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated

Authors:

Campos AC, Ortega Z, Palazuelos J, Fogaça MV, Aguiar DC, Díaz-Alonso J, Ortega-Gutiérrez S, Vázquez-Villa H, Moreira FA, Guzmán M, Galve-Roperh I, Guimarães FS.

Abstract:

Cannabidiol (CBD), the main non-psychotomimetic component of the plant

Cannabis sativa, exerts therapeutically promising effects on human
mental health such as inhibition of psychosis, anxiety and depression.
However, the mechanistic bases of CBD action are unclear. Here we
investigate the potential involvement of hippocampal neurogenesis in the
anxiolytic effect of CBD in mice subjected to 14 d chronic
unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg
i.p., 2 h after each daily stressor) increased hippocampal progenitor
proliferation and neurogenesis in wild-type mice. Ganciclovir
administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which
express thymidine kinase in adult neural progenitor cells, abrogated
CBD-induced hippocampal neurogenesis. CBD administration prevented the
anxiogenic effect of CUS in wild type but not in GFAP-TK mice as
evidenced in the novelty suppressed feeding test and the elevated plus
maze. This anxiolytic effect of CBD involved the participation of the
CB1 cannabinoid receptor, as CBD administration increased hippocampal
anandamide levels and administration of the CB1-selective antagonist
AM251 prevented CBD actions. Studies conducted with hippocampal
progenitor cells in culture showed that CBD promotes progenitor
proliferation and cell cycle progression and mimics the proliferative
effect of CB1 and CB2 cannabinoid receptor activation. Moreover,
antagonists of these two receptors or endocannabinoid depletion by fatty
acid amide hydrolase overexpression prevented CBD-induced cell
proliferation. These findings support that the anxiolytic effect of
chronic CBD administration in stressed mice depends on its proneurogenic
action in the adult hippocampus by facilitating
endocannabinoid-mediated signalling.