Table 3.
Neuropathology/neuroprotection studies using in vitro/ex vivo models
| Pathology | Model | Pathology | eCB/CB | Target | Reference |
|---|---|---|---|---|---|
| Excito-toxicity | Rat cortical neurons | Glutamate toxicity | CBD, THC | AO function | Hampson et al., 1998 |
| OHSCs | 4-Aminopyridine-induce seizures | CBD | Not determined | Jones et al., 2010 | |
| NMDA-induced excitotoxicity | 2-AG, PEA | GPR55, GPR18 and GPR119 (2-AG); PPARα (PEA) | Hohmann et al., 2019 | ||
| NMDA-induced excitotoxicity | AM-404 | Reduced glutamate release increase in 2-AG, AEA (via presynaptic CB1R?) | Saliba et al., 2019 | ||
| Kainate excitotoxicity | CBD | 5HT1A, TRPV1/2, PPARγ | Landucci et al., 2022 | ||
| Retina explants | Glutamte excitotoxicity | LLEA | Not determined | Duncan et al., 2010 | |
| Oxidative Stress | HT-22, cerebellar granule cells | Glutamate-, peroxide-induced oxidative stress | CBD, THC, WIN 55212, CP55940 | Direct AO effect | Marsicano et al., 2002 |
| HT-22 cells | Peroxidative stress | PEA | Unknown - possibly Akt activity | Duncan et al., 2009 | |
| Ischemia | HT-22 cells | OGD | CBD | Not determined | Sun et al., 2017 |
| Primary cortical neurons | OGD | N-stearoyl-tyrosine | Reduced FAAH activity, inhibition of anandamide transporter | Cui et al., 2017 | |
| Primary cortical neurons | OGD | WIN 55212-2 | CB1/CB2-independent | Nagayama et al., 1999 | |
| OHSCs | OGD | THC, CBD | PPARγ, 5-HT1A and TRPV2 | Lana et al., 2022 | |
| OGD | Bedrocan®, THC, CBD | CBD neuroprotection involved PPARγ, 5-HT1A and TRPV2 THC toxicity involved CB1 | Landucci et al., 2021 | ||
| Inflammation | OHSCs | Secondary to kainate excitotoxicity | CBD | 5-HT1A, TRPV1/2, and PPARγ | Landucci et al., 2022 |
| Secondary to NMDA excitotoxicity | 2-AG, AEA, THC and AM630 | Inhibited microglial chemotaxis (2-AG) via CB2 | Cabral et al., 2008 | ||
| LPS | CBD | Inhibited LPS-mediated vasodilation, reduced leukocyte margination | Ruiz-Valdepeñas et al., 2011 | ||
| Infection | Amoeba | Infection | eCBs | Inhibited amoeba chemotaxis & growth via CB2 | Dey et al., 2010 |
| AD/PD | HEK293 | Hyperphosphorylated tau | JWH133 | Decreased tau phosphorylation | Wang et al., 2018 |
| STHdhQ7/Q7 cells | thapsigargin | CBD | Increased cell viability | Patel et al., 2022 |
2-AG: 2-Arachidonoylglycerol; 5-HT1A: 5-hydroxytryptamine 1A; AD: Alzheimer’s disease; AEA: arachidonoylethanolamide; AO: Antioxidant; CB: cannabinoid; CB1/CB2: cannabinoid receptor 1/cannabinoid receptor 2; CBD: cannabigerol; eCB: endocannabinoid; FAAH: fatty acid amide hydrolase; LLEA: linoleoylethanolamine; LPS: lipopolysaccharide; OGD: oxygen-glucose deprivation; OHSCs: organotypic hippocampal slice cultures; PD: Parkinson’s disease; PEA: palmitoylethanolamine; PPARγ: peroxisome proliferator antigen receptor γ; THC: Δ9-Tetrahydro-cannabinol; TRPV2: transient receptor potential V1 or vanilloid receptor.