Table 2.

Main results from the studies with selective CB₂R agonists.

Reference	Cannabinoid	Dosage	Major Results		Model Used
Jayant et al., 2016 [62]	1-Phenylsatin	20 mg/kg p.o.	MWM test	↓ Latency escape ↑ Time spent in the target quadrant	In vivo experiments in rats exposed to STZ or AlCl3 + D-Gal
			Attentional set shifting test	↓ Attempts in REV1, EV stages
Cheng, Dong and Liu, 2014 [63]	BCP	48 mg/kg p.o.	↓ Escape latency, distance traveled (MWM) Dose-dependent ↓ in Aβ deposition in cerebral cortex, hippocampus ↓ Astrogliosis, microglial activation, COX-2 ↓ TNF-a, IL-1β		In vivo experiments in APP/PS1 mice
del Cerro et al., 2018 [64]	PGN33	2.5 nM 5 nM 7.5 nM 10 nM	Dose-dependent inhibition of uncontrolled proliferation of AD lymphoblasts ↓ Neuroblastoma cell death rate		In vitro experiments in lymphoblasts isolated from AD patients and in Aβ-treated SH-SY5Y cells
Li et al., 2019 [65]	JWH-015	0.5 mg/kg i.p.	Improvement in recognition of new objects, no improvement in spatial memory (NOR, MWM) Inhibition of cortical microglia activation, conversion from M1 to M2 phenotype		In vivo experiments in transgenic APP/PS1 mice
Çakır et al., 2019 [66]	JWH-133	0.2 mg/kg i.p.	↓ Escape latency, distance traveled (MWM) ↓ Caspase-3, p-TAU, Aβ, TNF-a, IL-1β		In vivo experiments in OKA-treated rats with hyperphosphorylated TAU
Köfalvi et al., 2016 [67]	JWH-133	30 nM–1 μΜ	↑ Glucose uptake in hippocampal astrocytes and neurons in vitro and hippocampal slices of young and middle-aged mice ex vivo by CB2R agonists, blocked by AM630 ↑ Glucose uptake in 12-month-old wild-type mice by selective agonists and COX-2 inhibitor, blocked by AM630 ↑ Glucose uptake in TgAPP 2567 mice only by CB2R agonists ↑ Brain glucose uptake in middle-aged mice by JWH133		In vitro experiments in primary cortical astrocytes and neurons, and acute hippocampal slices and in vivo experiments in young adult male C57Bl/6j and CD-1 mice, middle-aged C57Bl/6j mice, TgAPP-2576 mice
	GP1a (non-selective CB2R agonist)	100 nM
	AM630 (CB2R antagonist)	1 μΜ
Raïch et al., 2022 [68]	JWH-133	100 nM	Formation of CB2-OX1-heteromers Non-additive ↓ in cAMP levels by co-activation of CB2R and OX1R Potentiation of CB2R activation by OX1R antagonism ↑ Expression of CB2-OX1-heteromers in AD-model microglia		In vitro experiments in HEK-293T cells and microglial APPSw/Ind cells and in vivo experiments in APPSw/Ind transgenic mice

Abbreviations: Aβ: amyloid beta; AD: Alzheimer’s disease; AlCl₃: aluminum chloride; BCP: β-caryophyllene; COX-2: cyclooxygenase-2; D-Gal: D-galactosidase; EV: extra-dimensional; IL-1β: interleukin-1β; i.p.: intraperitoneally; MWM: Morris water maze; NF-κB: nuclear factor-κB; NOR: novel object recognition; OKA: okadaic acid; p.o.: per os; p-TAU: phosphorylated TAU; REV1: reversal 1; TLR4: toll-like receptor 4; TNF-a: tumor necrosis factor-a.