Cannabidiol (CBD) and cannabigerol (CBG) have antitumor activity on cholangiocarcinoma (CCA) in vitro, according to a new study published in Biomolecules. The researchers found that each compound uses a distinct cell death pathway to inhibit CCA.

“We found that both CBD and CBG were effective in inhibiting cholangiocarcinoma cells in vitro in a dose-dependent manner, with CBG being significantly more effective at the same dose as CBD across several functional assays,” the authors said.

“CBD and CBG induce their cytotoxic effects via different mechanisms, with CBD stimulating autophagic and apoptotic pathways and CBG stimulating only apoptotic pathways.”

The research team employed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays to assess the effect of 24 to 48 hours of treatment with CBD and CBG on proliferation, migration, and invasion of HuCC-T1 cells, Mz-ChA-1 cells (CCA cell lines) and H69 cells (immortalized cholangiocytes).

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Both cannabinoids were immediately effective at inhibiting cancer growth, although CBG was more active at lower doses. Moreover, both compounds enhanced apoptosis and inhibited mitosis in the CCA cells.

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Each compound had a distinct mechanism of action, with CBD upregulating type 2 cell death (autophagic degeneration) and CBG enhancing type 1 cell death (programmed apoptosis). The authors observed that the cellular signaling method differs between the compounds, with CBD using mitochondrial-dependent caspase activation and CBG activity being independent of mitochondria.

However, at the dosages employed, CBD and CBG also showed cytotoxicity in nonmalignant cholangiocytes, which has also been observed with the US Food and Drug Administration-approved version of CBD epidolex, leading to dosage limitations of that compound.


Viereckl MJ, Krutsinger K, Apawu A, et al. Cannabidiol and cannabigerol inhibit cholangiocarcinoma growth in vitro via divergent cell death pathways. Biomolecules. Published online June 20, 2022. doi:10.3390/biom12060854