In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells

Abstract

(‒)-Cannabidiol (CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its non-psychoactiveness and therapeutic potential, partly along with some anecdotal—if not scientific or clinical—evidence on the prevention and treatment of neurological diseases, have led researchers to investigate the biochemical actions of CBD on neural cells. This review summarizes the previously reported mechanistic studies of the CBD actions on primary neural cells at the in vitro cell-culture level. The neural cells are classified into neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells, and the CBD effects on each cell type are described. After brief introduction on CBD and in vitro studies of CBD actions on neural cells, the neuroprotective capability of CBD on primary neurons with the suggested operating actions is discussed, followed by the reported CBD actions on glia and the CBD-induced regeneration from neural stem cells. A summary section gives a general overview of the biochemical actions of CBD on neural cells, with a future perspective. This review will provide a basic and fundamental, but crucial, insight on the mechanistic understanding of CBD actions on neural cells in the brain, at the molecular level, and the therapeutic potential of CBD in the prevention and treatment of neurological diseases, although to date, there seem to have been relatively limited research activities and reports on the cell culture-level, in vitro studies of CBD effects on primary neural cells.

Effect of Cannabidiol in LPS-induced toxicity in astrocytes: Possible role for cannabinoid type-1 receptors

“…It attenuates NF-κB phosphorylating transcription factor subunit p65 in LPS-stimulated glial cells (Cardinal von Widdern et al, 2020). Also, CBD may inhibit ROS release in LPS-stimulated cells by limiting NADPH production and glucose uptake regarding the fact that glucose is an essential element in the regeneration of NADPH used by NADPH oxidase (NOX) to catalyze ROS production (Kim et al, 2021a, Kim et al, 2021b). Yet, the exact mechanisms by which CBD inhibits the over-production of intercellular ROS induced by LPS remain unresolved.…”

“…After its discovery, research on CBD's therapeutic potential was accelerated, highlighting its anti-psychotic, anti-epileptic, anxiolytic, and anti-convulsive effects (Chan and Duncan, 2021). Recently, studies have demonstrated CBD's potent antioxidant and anti-in ammatory properties in vitro and in vivo (Rajan et al, 2016, Atalay et al, 2020, Kim et al, 2021a. CBD has neuroprotective properties mediated by its effect on the cannabinoid receptors type 2 (CB2) directly and/or its effect on the release of endocannabinoids such as anandamide.…”

Supraphysiologic doses of 17β-Estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism

“…Primary microglia and neurons were extracted from the brains of neonatal female C57/BL6J mice (n = 32; 1-2 days old) as previously described [27]. The microglia were cultured in Neurobasal-A medium containing 2% B27, 2-mM L-glutamine, 50-U/ml penicillin, and 50-U/ml streptomycin (Gibco, USA).…”

<b><i>Cannabis sativa</i></b> and Cannabidiol: A Therapeutic Strategy for the Treatment of Neurodegenerative Diseases?

“…Recently, the neuroprotective capability of CBD against OS, as well as its toxicity profile on in vitro culture, is systematically pursued. Although CBD showed both neurotoxic and neuroprotective effects on hippocampal neurons, the use of low-concentrated (i.e., 5 μM) CBD did not cause toxic effects and significantly rescued the neurons from OS, confirming its neuroprotection capability [ 26 ].…”