Skip to main content
. 2024 Aug 7;25(16):8630. doi: 10.3390/ijms25168630

Table 6.

Main results from the combination studies with agonists belonging to different classes.

Reference Cannabinoid Dosage Major Results Model Used
Elmazoglu et al., 2020 [100] AEA 1–1000 μΜ

  • ↑ Cell viability, ↓ ROS (URB597 > WIN55,212-2 ≈ CP55-940 > 2-AG ≈ AEA)

  • ↓ Aggregation of Aβ (URB597 ≈ AEA > rest of cannabinoids)

  • ↑ SOD, CAT, GPx, GRx and Nrf2

 In vitro experiments in rat hippocampal neurons—model of combined toxic hyperglycemia and Aβ1–42
2-AG
CP55-940
WIN55,212-2
URB597 (FAAH inhibitor)
Schubert et al., 2019 [101] Δ8-THC 250 nΜ–10 μM

  • Reduction in accumulated Aβ by Δ8-THC and Δ9-THC

  • CBD, DMCBD, CBGA, Δ9-THC suppressed pro-inflammatory response of microglial cells to LPS (EC50 < 10 μM)

  • Neuroprotection independent of CB1R and CB2R activation

 In vitro experiments in HT22 and MC65 cells after induction of C99 production
Δ9-THC
Δ9-THCA
CBD
CBDA
DMCBD
CBDV
CBG
CBGA
CBC
CBN
MCBN
Navarro-Dorado et al., 2016 [102] WIN55,212-2 0.2 mg/kg/day p.o. Combined action

  • Restoration of normal (↓) Col IV levels in anterior cortical positive vessels, ↓ Col IV vascular density

  • Restoration of the vasodilatory action of ACh

  • ↓ Microvascular lesions

 In vivo experiments in TgAPP AD mice
JWH-133
Stanciu et al., 2024 [103] JWH-133 0.2 mg/kg p.o. for over 90 days Combined action

  • Reduced cognitive decline and anxiety-like behavior (NOR and EPM tests)

  • ↓ Size and number of Aβ plaques, cerebral glucose metabolism, mTOR, CB2R

  • Enlarged astrocytes

  • ↑ M1 receptors

 In vivo experiments in APP/PS1 mice
Cannabixir® Medium Flos 2.5 mg/kg p.o. for over 90 days
Donepezil 0.65 mg/kg p.o.

Abbreviations: Aβ: amyloid beta; ACh: acetylcholine; AD: Alzheimer’s disease; AEA: anandamide; 2-AG: 2-arachidonylglycerol; CAT: catalase; CBC: cannabichromene; CBD: cannabidiol; CBDA: cannabidiol acid; CBDV: cannabidivarin; CBG: cannabigerol; CBGA: cannabigerolic acid; CBN: cannabinol; CB1R: cannabinoid receptor 1; CB2R: cannabinoid receptor 2; Col IV: collagen IV; DMCBD: dimethyl cannabidiol; EPM: elevated plus maze; FAAH: fatty acid amide hydrolase; GPx: glutathione peroxidase; GRx: glutaredoxin; LPS: lipopolysaccharide; MCBN: cannabinol methyl ether; mTOR: mammalian target of rapamycin; NOR: novel object recognition; Nrf2: nuclear factor erythroid 2-related factor 2; p.o.: per os; ROS: reactive oxygen species; SOD: superoxide dismutase; Δ9-THC: tetrahydrocannabinol; Δ9-THCA: tetrahydrocannabinolic acid.