Patients with active eosinophilic esophagitis had reduced MGL enzyme activity and elevated 2-AG levels in their esophagus, and blocking CB2 receptors reduced eosinophil infiltration in mice.
Gastroenterologists, allergists treating EoE, endocannabinoid system researchers
What the researchers found
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.
Why it matters
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.
The numbers in context
MGL expression decreased in active EoE biopsies; 2-AG levels increased vs controls; CB2 antagonism reduced eosinophil infiltration in mouse model; findings consistent across human biopsies, in vitro, and mouse models
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
Preliminary: mechanistic study combining human biopsies with animal and cell models, but no clinical intervention data.
When this study was published
2025 publication
The bigger picture
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.
Questions still open
- Should EoE patients be counseled about potential worsening with cannabis use?
- Could CB2 antagonists become a treatment option for EoE?
Read the original research
The Endocannabinoid System Drives Eosinophil Infiltration During Eosinophilic Esophagitis.
Cellular and molecular gastroenterology and hepatology, 19(8), 101515
Citation
Gruden, Eva; Kienzl, Melanie; Danner, Laura; Kaspret, David Markus; Pammer, Anja; Ristic, Dusica; Kindler, Oliver; Doyle, Alfred D; Wright, Benjamin L; Taschler, Ulrike; Thomas, Dominique; Gurke, Robert; Baumann-Durchschein, Franziska; Konrad, Julia; Blesl, Andreas; Schlager, Hansjörg; Bärnthaler, Thomas; Kargl, Julia; Schicho, Rudolf. (2025). The Endocannabinoid System Drives Eosinophil Infiltration During Eosinophilic Esophagitis.. Cellular and molecular gastroenterology and hepatology, 19(8), 101515. https://doi.org/10.1016/j.jcmgh.2025.101515
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