The differential effects of CBD and CBDA on viability and mRNA expression in colorectal cancer cells

Title (eng)
The differential effects of CBD and CBDA on viability and mRNA expression in colorectal cancer cells
Author
Christine Heinzle
Author
Kathrin Geiger
Author
Reinhard Ertl
Author
Eva Maria Brandtner
Author
Andreas Leiherer
Author
Stella Gaenger
Author
David Schmidmayr
Author
Heinz Drexel
Author
Axel Muendlein
Abstract (eng)
Background Cannabinoids have attracted significant attention for their potential therapeutic application in cancer research. However, recent studies have reported antitumor activity of cannabidiolic acid (CBDA)—the acidic precursor of CBD—in breast cancer cells, involving modulation of cyclooxygenase signaling. To our knowledge, no investigations have examined the effects of CBDA on RNA expression and signaling pathways in colorectal cancer (CRC) cells. Therefore, we aimed to investigate the effects of CBD, CBDA, and a CBDA-rich Cannabis sativa (C.s). extract on the growth and gene expression in CRC cell lines. Methods We assessed cell viability and clonogenic growth of the CRC cell lines HCT116 and DLD1 following treatment with pure CBD, pure CBDA, a CBDA-rich C.s. extract (CBDA/CBD ratio 20:1), and a corresponding mixture of pure CBDA/CBD. RNA sequencing was performed to analyze differentially expressed genes (DEGs) and the cell signaling pathways affected by these treatments. Results Of all tested compounds, CBD exhibited the strongest cytotoxic effect in both cell lines, whereas CBDA demonstrated minimal toxicity, particularly in HCT116 cells. Furthermore, we observed a greater inhibitory effect of the CBDA-rich C.s. extract on HCT116 cell growth compared to the CBDA/CBD mixture. RNA sequencing analysis revealed that CBD had the most pronounced impact on gene expression, while CBDA had the least. Notably, treatment with the C.s. extract resulted in a higher number of DEGs than the CBDA/CBD mixture in HCT116. Gene expression analysis indicated an upregulation of the Wnt and Hippo signaling pathways following CBD treatment. Additionally, CBDA, CBD/CBDA (1:20), and the C.s. extract primarily induced metabolic processes in DLD1 cells, suggesting a distinct metabolic response. Conclusion Our findings showed that CBD exerts stronger effects on cell survival and gene expression in CRC cells than CBDA, which showed only limited activity. Moreover, the CBDA-rich C.s. extract exhibited greater efficacy than the CBDA/CBD mixture. More research is needed to further elucidate the impact of cannabinoids on CRC cell biology and signaling pathways.
Keywords (eng)
CBDCBDACannabis SativaPlant ExtractColorectal CancerEntourage EffectRNA Sequencing
Type (eng)
journal article
Language
[eng]
Persistent identifier
https://phaidra.vetmeduni.ac.at/o:5369
DOI
10.1186/s42238-026-00391-2
Is in series
Title (eng)
Journal of Cannabis Research
Volume
8
ISSN
2522-5782
Issued
2026
Number of pages
17
Publication
Springer
Version type (eng)
version of record (published version)
Date issued
2026
Access rights (eng)
open access
License
CC BY 4.0 International
Rights statement (eng)
© The Author(s) 2026