TABLE 3.

CBD on AD, in vivo study.

Animal model of AD	AD pathogenesis	CBD dose and way of administration	Frequency of dosing	Major findings	Ref.
3–5-month-old C57BL/6J mice	Implantation of 10 ng of Aβ (1–42) into the right dorsal hippocampus	2.5 or 10 mg kg−1, i.p	Daily, 7 consecutive days, dosing started at day 3 post inoculation	Suppression of neuroinflammation via reducing glial fibrillary acidic protein (GFAP) mRNA, iNOS, and IL-1β protein expression	Esposito et al. (2007)
Adult male Sprague–Dawley rats (300–350 g)	Intrahippocampal injection of 30 ng fibrillar Aβ (1–42) peptide	i.p., 10 mg/kg	Daily, 15 consecutive days	Restoration of hippocampal neurogenesis via activating the PPARγ axis	Esposito et al. (2011)
C57/Bl6 mice, 3 months old	Intraventricular injection of 2.5 μg of fibrillar Aβ	i.p., 20 mg/kg	Daily for first 7 days, alternate days following 15 days, treatment started at Day 1	Promotes microglial cell migration, prevention of Aβ-induced cognitive deficit as determined by in the Morris water maze behavioral study	Martín-Moreno et al. (2011)
APPxPS1 mice, 6 months old male	Genetically modified	i.p., 20 mg/kg	Daily, 3 weeks	Rescue of social recognition and object recognition deficits	Cheng et al. (2014)
APPxPS1 mice, 2.5 months old	Genetically modified	Oral, 20 mg/kg	8 months	Rescue of social recognition and object recognition deficits	Cheng and Spiro et al. (2014)
APPxPS1 mice, 12 months old	Genetically modified	i.p., 50 mg/kg	Daily, 3 weeks	On social recognition memory and spatial learning deficits, moderate brain region-specific reductions in insoluble Aβ40 levels	Watt et al. (2020)
APPxPS1 mice	Genetically modified	CBD-rich cannabis extract (at a dose of 0.75 mg/kg of CBD)	—	Preservation of memory, reduced astrogliosis, microgliosis, and inflammatory-related molecules in treated mice, THC + CBD exhibits better than individual	Aso et al. (2015)
12-month-old APPxPS1 female mice	Genetically modified	i.p., 5 mg/kg CBD	Daily, 3 weeks	Reverses object recognition memory deficits	Coles et al. (2020)
5xFAD mice	Genetically modified	—	—	Interleukin (IL)-33 and triggering receptor expressed on myeloid cell 2 (TREM2) which reduces cognitive decline	Khodadadi et al. (2021)
Male 6-month-old APP/PS1 mice	Genetically modified	i.p. with 5 mg/kg BW of CBD	Daily for 30 days	RNAseq with hippocampus of six-month-old APP/PS1 mice	Hao and Feng (2021)
				Reduction of Aβ plaques, markedly enhanced mitochondrial autophagy observed in hippocampal neurons
Male Wistar rat	Streptozotocin (STZ)-induced AD model	i.p. treatment of CBD (20 mg/kg BW)	—	Enhances the brain glucose metabolism	de Paula Faria et al. (2022)
4-month-old TAU58/2 male mice	Genetically modified (tauopathy model)	50 mg/kg CBD i.p. administration	3 weeks	Did not affect behavioral changes	Watt, et al. (2020)
14-month-old TAU58/2 female mice	Genetically modified (tauopathy model)	100 mg/kg CBD i.p. administration	3 weeks	Improving spatial memory along with reducing anxiety-like behaviors and contextual fear-associated freezing	Kreilaus et al. (2022)