Cannabidiol (CBD) is known to activate aryl hydrocarbon receptor (AhR) and expression of cytochromes P450 (CYP) 1A. This study examined the effect of cannabigerol (CBG) on the AhR/CYP1A pathway in HepG2 cells, human hepatocytes, and normal human epidermal keratinocytes (NHEK cells), and the action of CBG was compared to that of CBD. The results confirmed CBD activated both AhR and CYP1A1 transcription in transfected HepG2 cells, and it increased the levels of CYP1A1 mRNA in HepG2 and NHEK cells, and the levels of CYP1A1 and CYP1A2 mRNA in hepatocytes. Moreover, CBD upregulated the protein levels of CYP1A1 and CYP1A2 in HepG2 cells and hepatocytes, respectively, but these effects were only accompanied by a slight increase in the activity of CYP1A enzymes. In contrast to CBD, CBG had a negligible effect on AhR activity and CYP1A1 transcription. Despite this, CBG elevated the CYP1A mRNA levels in all three cell models, but this effect was weaker than that of CBD, and it did not result in relevant changes in the protein levels or activity of CYP1A. We conclude that CBG is a poor modulator of the AhR/CYP1A pathway in vitro , and its effect on the pathway in vivo remains to be explored. • Effect of cannabidiol (CBD) and cannabigerol (CBG) on AhR/CYP1A pathway was tested. • HepG2 cells, human hepatocytes and normal human epidermal keratinocytes were used. • CBD, unlike CBG, activated AhR and CYP1A1 transcription in transfected HepG2 cells. • CBD and, to a lesser extent, CBG increased CYP1A mRNA levels in all cell types. • CBD, unlike CBG, upregulated CYP1A1 in HepG2 cells and CYP1A2 in human hepatocytes.
Vrba et al. (Fri,) studied this question.