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. Despite its therapeutic promise, effective pharmacological activation of the ECS remains challenging. Objectives This study aimed 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. Additionally, we assessed the clinical significance of ECS-related protein receptors in the progression of EAC. Design In vitro experimental models combined with clinical samples analyses. Methods We utilized in vitro models, including human esophageal epithelial cell lines exposed to DCA and a Barrett’s esophagus gastroesophageal reflux (GER) model subjected to low pH and a bile acid cocktail. Patient-derived samples were analyzed to investigate the clinical association of ECS pathway markers with EAC progression. Experimental models were treated with varying ratios of phyto-cannabinoids and terpenes. Endpoints included assessment of DNA damage, mitochondrial membrane potential, and ROS production to identify…
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