Publication Name	World Journal of Gastroenterology
Manuscript ID	111455
Country	United States

Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Optimal cannabinoid-terpene combination ratios suppress mutagenicity of gastric reflux in normal and metaplastic esophageal cells
Manuscript Source	Unsolicited Manuscript
All Author List	Aaron Goldman, Gabriel Gonzalez, Svetlana A Karpova, Leutz Buon, Masood A Shammas, Hiroshi Mashimo, Markus H Frank and Natasha Y Frank
Funding Agency and Grant Number	Funding Agency Grant Number National Institutes of Health No. R01EY025794 National Institutes of Health No. R01HL161087 National Institutes of Health No. P01AG071463 National Institutes of Health No. 1K01CA226375-01A1 Veterans Administration Research and Development Merit Review Awards No. 1I01BX000516 Veterans Administration Research and Development Merit Review Awards No. 1I01RX000989 Veterans Administration Research and Development Merit Review Awards No. 1I01BX006004
Corresponding Author	Natasha Y Frank, Department of Medicine, VA Boston Healthcare, 1400 VFW Parkway, Building 3, Suite 2A105, Boston, MA 02132, United States. nyfrank@bwh.harvard.edu
Key Words	Gastroesophageal reflux disease; Bile acids; DNA damage; New therapeutics; Cannabinoids; Reactive oxygen species; DNA repair
Core Tip	Activation of the endocannabinoid system (ECS) with specific cannabinoid-terpene combinations and ratios has been shown to protect esophageal cells from bile acid-induced DNA damage and mutations, which are key drivers of esophageal adenocarcinoma (EAC). In vitro models revealed that a 1:5 ratio of cannabigerol to phytol or β-caryophyllene significantly reduced DNA damage and oxidative stress while preserving mitochondrial function. This combination also promoted apoptosis in damaged cells, while the ECS receptor expression patterns correlated with EAC progression. These findings indicate that ECS modulation may represent a novel therapeutic strategy for EAC and related conditions.
Citation	Goldman A, Gonzalez G, Karpova SA, Buon L, Shammas MA, Mashimo H, Frank MH, Frank NY. Optimal cannabinoid-terpene combination ratios suppress mutagenicity of gastric reflux in normal and metaplastic esophageal cells. World J Gastroenterol 2026; In press

Received	2025-07-01 09:47
Peer-Review Started	2025-07-01 09:48
First Decision by Editorial Office Director	2025-07-29 09:48
Return for Revision	2025-07-29 09:48
Revised	2025-09-12 14:45
Publication Fee Transferred
Second Decision by Editor	2026-02-04 02:41
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-02-04 10:02
Articles in Press	2026-02-04 10:02
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
Open Access	This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
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