Substance Use Disorders Are Associated With Increased Long‐Term Risks of Gastroesophageal Reflux Disease Phenotypes: A Global Propensity‐Matched Cohort Study

BACKGROUND: Substance use disorders (SUDs) may alter esophagogastric function, yet their long-term impact on gastroesophageal reflux disease (GERD) phenotypes and complications has remained unclear. The aim of this study is to evaluate whether SUDs are associated with increased risk of GERD, non-erosive reflux disease (NERD), erosive esophagitis (EE), Barrett's esophagus (BE), and GERD-related complications. METHODS: Using the TriNetX electronic health record network, we identified adults with documented SUDs and matched them 1:1 to drug-free controls using propensity scores. Cumulative incidence (%) at 1-, 5-, 10-, and 20-year and hazard ratios (HRs) were used to qualify long-term disease burden and time-to-event associations. Analyses were performed overall and separately for opioids, cannabis, cocaine, other stimulants, and sedatives. KEY RESULTS: Across 540,630 matched pairs, SUDs were associated with significantly higher 20-year cumulative risks of GERD (13.58% vs. 6.41%, p < 0.0001), NERD (13.25% vs. 6.20%, p < 0.0001), and EE (2.07% vs. 1.03%, p < 0.0001) as compared with drug-free controls. HRs persistently elevated in GERD and NERD across follow-up. Opioids showed the strongest associations across GERD phenotypes (11.72% vs. 6.77% at 20 years, p < 0.0001), followed by cannabis and sedatives, whereas stimulants and cocaine showed weaker or delayed effects. Risk elevations for Barrett's esophagus, esophageal stricture, and esophageal adenocarcinoma (EAC) were low but increased cumulatively over long-term follow-up. CONCLUSIONS AND INFERENCES: SUDs are associated with increased long-term risk of GERD, NERD, and EE, with opioids, cannabis, and sedatives demonstrating the strongest associations. Clinicians should consider substance exposure when evaluating and managing patients with gastroesophageal reflux.