The Endocannabinoid System Drives Immune Cell Infiltration in Eosinophilic Esophagitis

In esophageal biopsies from patients with active eosinophilic esophagitis (EoE), the enzyme that breaks down the endocannabinoid 2-AG (monoacylglycerol lipase, MGL) was decreased, leading to elevated 2-AG levels. When MGL was inhibited in epithelial cells, they developed a pro-inflammatory profile that attracted eosinophils via the CB2 receptor. In a mouse EoE model, blocking CB2 reduced eosinophil infiltration. The findings help explain why cannabis users with EoE may have worse inflammatory features after treatment.

Multi-method study combining human biopsy analysis (MGL expression, 2-AG levels, enzyme activity), in vitro epithelial cell experiments (eosinophil migration assays), and an inducible mouse EoE model with MGL inhibition and CB receptor antagonism.

This is the first study to connect altered endocannabinoid signaling to eosinophilic esophagitis. The finding that cannabis use may worsen EoE inflammation through CB2-mediated eosinophil recruitment has direct implications for the growing number of cannabis users with this condition.

EoE is increasingly common and its relationship with cannabis use is largely unrecognized. If cannabinoids can drive the inflammatory process that defines EoE, this creates a clinical concern as cannabis use expands alongside rising EoE diagnoses.

Translational study combining human observational data with mechanistic animal and cell work. Mouse EoE models do not fully replicate human disease. Cannot determine whether exogenous cannabis use would have the same effects as elevated endogenous 2-AG.