Cannabinoid (CB)
ligands have demonstrated neuroprotective properties. In this study we compared the effects of a diverse set of CB
ligands against β
amyloid-mediated neuronal toxicity and activated microglial-
conditioned media-based neurotoxicity in vitro, and compared this with a capacity to directly alter β
amyloid (Aβ) fibril or aggregate formation.
Neuroblastoma (SH-SY5Y) cells were exposed to Aβ1-42 directly or microglial (BV-2 cells)
conditioned media activated with
lipopolysaccharide (LPS) in the presence of the
CB1 receptor-selective agonist ACEA,
CB2 receptor-selective agonist
JWH-015, phytocannabinoids Δ(9)-THC and
cannabidiol (CBD), the
endocannabinoids 2-arachidonoyl
glycerol (2-AG) and
anandamide or putative GPR18/GPR55
ligands O-1602 and
abnormal-cannabidiol (
Abn-CBD). TNF-α and
nitrite production was measured in BV-2 cells to compare activation via LPS or
albumin with Aβ1-42. Aβ1-42 evoked a concentration-dependent loss of cell viability in SH-SY5Y cells but negligible TNF-α and
nitrite production in BV-2 cells compared to
albumin or LPS. Both
albumin and LPS-activated BV-2
conditioned media significantly reduced neuronal cell viability but were directly innocuous to SH-SY5Y cells. Of those CB
ligands tested, only 2-AG and CBD were directly protective against Aβ-evoked SH-SY5Y cell viability, whereas
JWH-015,
THC, CBD,
Abn-CBD and
O-1602 all protected SH-SY5Y cells from BV-2
conditioned media activated via LPS. While CB
ligands variably altered the morphology of Aβ fibrils and aggregates, there was no clear correlation between effects on Aβ morphology and neuroprotective actions. These findings indicate a neuroprotective action of CB
ligands via actions at microglial and neuronal cells.