Optimal cannabinoid-terpene combination ratios suppress mutagenicity of gastric reflux in normal and metaplastic esophageal cells
Abstract
BACKGROUND Esophageal adenocarcinoma (EAC) frequently arises from chronic exposure to acid and bile reflux, with secondary bile acids, such as deoxycholic acid (DCA), contributing to its pathogenesis through mechanisms involving reactive oxygen species (ROS), oxidative DNA damage, and resistance to apoptosis. The human endocannabinoid system (ECS) regulates diverse anti-inflammatory, antioxidant, and analgesic pathways implicated in disease modulation and may counteract the harmful effects of gastroesophageal reflux. Despite its therapeutic promise, effective pharmacological activation of the ECS remains challenging. AIM To evaluate whether specific cannabinoid-terpene combinations targeting the ECS could attenuate the mutagenic and cytotoxic effects of bile acid-induced stress in esophageal cell models, and to assess the clinical significance of ECS-related protein receptors in the progression of EAC. METHODS Human esophageal epithelial cells exposed to DCA, as well as a Barrett’s esophagus cell line subjected to low potential of hydrogen and a bile acid cocktail, were treated with various ratios of phyto-cannabinoids and terpenes. Endpoints included DNA damage, mitochondrial membrane potential, and ROS production to identify optimal compound combinations. Expression of ECS-related receptor proteins in clinical samples was assessed by immunohistochemistry. RESULTS A 1:5 ratio of cannabigerol to phytol significantly reduced DCA-induced DNA damage, preserved mitochondrial…
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