A study identifies the endocannabinoid system as a potential therapeutic target in severe acute pancreatitis

A study led by researchers from the Respitatory and Immune Repair (REPAIR) group at the Germans Trias i Pujol Research Institute (IGTP), in collaboration with researcher Daniel Closa from IIBB-CSIC, Enrique de-Madaria from ISABIAL and CIBEREHD, and researcher Karina Cárdenas-Jaen from Miguel Hernández University, has identified alterations in the endocannabinoid system associated with the most severe forms of acute pancreatitis. The findings, published in The Journal of Pathology, describe a disruption linked to the most severe forms of the disease and point to the potential of the endocannabinoid system as both a biomarker of severity and a future therapeutic target.

Acute pancreatitis is an inflammatory disease that, in its most severe cases, can trigger systemic complications and affect other organs, including the lungs. In this work, the research team studied the role of the endocannabinoid system in regulating the inflammatory response during the disease using a preclinical model.

The study shows that circulating levels of the endocannabinoid 2-AG decrease in patients who later develop severe acute pancreatitis. This pattern was also observed in the experimental model used by the researchers.

In this context, restoring 2-AG levels reduced both local and systemic inflammation, modulated immune cell responses, and decreased lung damage associated with the disease.

In addition, the findings identify distinct functions of the cannabinoid receptors CB1 and CB2 in regulating the inflammatory pathways involved in acute pancreatitis, further supporting the role of the endocannabinoid system in the pathophysiology of the disease.

Overall, the study "opens new avenues for understanding why some patients progress to more severe forms of acute pancreatitis and highlights the potential of the endocannabinoid system both as a prognostic biomarker and as a possible therapeutic strategy", explains Paula Goncalves-Romeu, first author of the study.

Reference

Goncalves-Romeu, P., Cárdenas-Jaen, K., de-Madaria, E., Hernández, J.M., Fluvià, L., Torres-Ribas, L., Closa, D. and Guillamat-Prats, R. (2026), Disrupted endocannabinoid signaling contributes to systemic inflammation in acute pancreatitis. J. Pathol. DOI: https://doi.org/10.1002/path.70076