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.

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 ].…”

Neutralization of Cannabidiol Neurotoxicity in Neuron‐Astrocyte Sandwich Coculture

“…(-)-Cannabidiol (2-[(1R,6R)-3-methly-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol, CBD), one of the major cannabinoids in the Cannabis genus, has ethnopharmacologically been suggested to have various health benefits, including anti-cancer, anti-epileptic, anxiolytic, anti-inflammatory, and neuroprotective effects. [1][2][3][4][5][6] Unlike tetrahydrocannabinol (THC) that is another main cannabinoid extracted from Cannabis, CBD is not psychoactive. According to the WHO Expert Committee on Drug Dependence, CBD has low toxicity and good safety profiles (e.g., no alterations of heart rate, blood pressure, and body temperature), but some clinical studies have reported mild DOI: 10.1002/adbi.202300090 adverse effects of CBD in the nervous system (e.g., headache, dizziness, and somnolence) and in the gastrointestinal system (e.g., diarrhea and nausea).…”

“…The neurotoxicity studies on CBD would be particularly informative and beneficial in the healthcare sector, considering much interest in CBD against neurological diseases, [6] as well as recent U.S. Food and Drug Administration (FDA) approval of CBD as a treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex in patients 1 year of age or older. [7][8][9] However, fundamental studies on the cytotoxicity of CBD in neurons, a major cell type that executes main functional roles in the nervous system, still have been limited.…”