A combination of the cannabinoid cannabigerol (CBG) and certain terpenes significantly reduced DNA damage, oxidative stress and genomic instability caused by components of gastric reflux in human esophageal cells, according to a peer-reviewed study.
The study, published in the World Journal of Gastroenterology by researchers affiliated with Brigham and Women’s Hospital, VA Boston Healthcare, Harvard Medical School, Dana-Farber Cancer Institute and other institutions, examined whether specific cannabinoid-terpene combinations could protect cells from damage associated with gastroesophageal reflux.
Researchers focused on deoxycholic acid (DCA), a secondary bile acid present in gastric reflux that can generate reactive oxygen species, damage DNA and contribute to processes involved in the development of esophageal adenocarcinoma.
Using normal human esophageal epithelial cells, researchers tested various cannabinoids and terpenes at different ratios. A combination of CBG and phytol at a 1:5 ratio significantly reduced DCA-induced DNA damage and helped reverse disruption of mitochondrial membrane function.
CBG combined with myrcene or beta-caryophyllene also reduced markers of DNA damage.
Researchers additionally found that CBG and phytol significantly decreased reactive oxygen species generated by DCA. When cells were exposed to DCA over longer periods, treatment with the 1:5 CBG-phytol combination significantly reduced newly acquired gene amplifications and deletions, indicating reduced genomic instability and mutagenicity.
The combination also appeared to interfere with the survival of damaged cells. Esophageal cells exposed to DCA were able to resume proliferation after the bile acid was removed, potentially allowing cells carrying acquired DNA alterations to multiply. Cells treated with CBG and phytol showed reduced proliferation after DCA exposure and were more likely to undergo apoptosis, or programmed cell death.
Researchers conducted a separate series of experiments using cells associated with Barrett’s esophagus, a condition linked to an increased risk of esophageal adenocarcinoma.
Those cells were exposed to an acidic environment and a mixture of bile acids designed to mimic gastroesophageal reflux. Among the combinations tested, CBG with beta-caryophyllene at a 1:5 ratio produced the greatest reduction in reactive oxygen species and significantly reduced subsequent DNA damage.
The researchers said the CBG and beta-caryophyllene combination reduced oxidative damage more effectively in their cell model than ursodeoxycholic acid, a bile acid used clinically for certain liver and biliary conditions.
The team also examined cannabinoid-related receptors in human tissue samples. CB1 receptor expression was significantly elevated in esophageal adenocarcinoma tissue compared with normal esophageal tissue, while several other G-protein coupled receptors potentially influenced by cannabinoids showed altered expression in Barrett’s esophagus and cancer samples.
The researchers concluded that carefully selected cannabinoid-terpene combinations may help suppress the mutagenic effects of gastric reflux and prevent damaged cells from continuing to proliferate.
