Glial Cells and Their Contribution to the Mechanisms of Action of Cannabidiol in Neuropsychiatric Disorders.
Pattern of expression and effects associated with the molecular targets potentially involved in CBD mechanism of action in glial cells. Schematic representation pointing the expression of 5-HT1A receptor, proteins of the endocannabinoid system (ECS) and the PPAR-γ receptor in astrocytes, microglia, oligodendrocytes and NG2 cells (Azmitia et al., 1996; Bernardo et al., 2000; Egertová et al., 2003; Zhang et al., 2011; Gonzalez-Reyes et al., 2013; Graves, 2013; Sharifi et al., 2013; Young et al., 2013; Ke et al., 2014; Fan and Agid, 2018; Duffy et al., 2017; Viudez-Martínez et al., 2018; Kong et al., 2019; Yang et al., 2019; Ding et al., 2020) (+) indicates that there is evidence that the protein has been found in the specific cell type (−) indicates the absence of evidence for the expression of the molecular target in the specific cell type. For the ECS, NAPE-PLD, FAAH and FABP are considered as the potential targets involved in the increased AEA availability induced by CBD treatment. The effects of CBD that have been shown to be dependent on 5-HT1A (Campos and Guimarães, 2008; Zanelati et al., 2010; Campos et al., 2013a; Rodrigues da Silva et al., 2020), on the ECS (Casarotto et al., 2010; Leweke et al., 2012; Stern et al., 2012; Campos et al., 2013b; Pazos et al., 2013; Sartim et al., 2016; Fogaça et al., 2018; Khan et al., 2020) or on PPAR-γ receptors (Esposito et al., 2011; dos-Santos-Pereira et al., 2016; Giacoppo et al., 2017; Sonego et al., 2018) are highlighted. CBD, Cannabidiol; 5-HT1A, 5-hydroxytryptophan 1 A receptor; ECS, endocannabinoid system; NAPE-PLD, N-acyl phosphatidylethanolamine-specific phospholipase D; FAAH, fatty-acid amide hydrolase; FABP, fatty acid binding protein; CB1/CB2, cannabinoid receptor one/cananbinoid receptor two; TRPV1, transient receptor potential vanilloid one; GPR55, G coupled receptor 55; PPAR-γ, Peroxisome proliferator-activated receptor-γ.