People with pancreatitis had higher blood levels of the endocannabinoid anandamide than healthy controls, while another endocannabinoid (2-AG) was lower in those reporting recent pain.
Endocannabinoid system researchers, gastroenterologists, pain medicine specialists
What the researchers found
In a case-control study of 231 participants, circulating anandamide (AEA) levels were significantly higher in pancreatitis patients compared to controls, with the highest levels in acute pancreatitis. Conversely, 2-AG levels were significantly lower in participants reporting abdominal pain in the past week, and pain intensity was inversely associated with both 2-AG and OEA concentrations.
Why it matters
This research maps how the body's own cannabinoid system responds to pancreatic disease and pain. The divergent patterns of AEA (elevated with disease) and 2-AG (depleted with pain) suggest the endocannabinoid system plays distinct roles in inflammation versus pain processing.
The numbers in context
231 participants across 5 groups; AEA significantly higher in all disease groups vs controls (p=0.03); 2-AG significantly lower in those with recent pain (p=0.02); AEA higher in women than men (p=0.0499); PEA higher in obese participants (p=0.003)
How the study worked
Case-control study within the PROCEED cohort, measuring serum levels of two endocannabinoids (AEA, 2-AG) and two paracannabinoids (OEA, PEA) across five groups: no pancreatic disease (n=56), suspected/indeterminate chronic pancreatitis (n=22), acute pancreatitis (n=33), recurrent acute pancreatitis (n=57), and definite chronic pancreatitis (n=63).
What this study cannot tell us
Cross-sectional design cannot determine whether endocannabinoid changes are a cause or consequence of disease. Relatively small group sizes. Serum levels may not reflect tissue-level endocannabinoid activity.
How to read the evidence
Preliminary: cross-sectional case-control design with moderate sample sizes, cannot establish causality.
When this study was published
2025 publication
The bigger picture
Understanding how endocannabinoid levels shift with disease and pain could eventually inform new treatment strategies, potentially including cannabinoid-based therapies for pancreatitis pain.
Questions still open
- Could targeting the endocannabinoid system offer pain relief for pancreatitis patients?
- Do endocannabinoid level changes precede or follow pancreatitis progression?
Read the original research
Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.
Cannabis and cannabinoid research, 10(1), 60-70
Citation
Goodman, Marc T; Lombardi, Christina; Torrens, Alexa; Bresee, Catherine; Saloman, Jami L; Li, Liang; Yang, Yunlong; Fisher, William E; Fogel, Evan L; Forsmark, Christopher E; Conwell, Darwin L; Hart, Phil A; Park, Walter G; Topazian, Mark; Vege, Santhi S; Van Den Eeden, Stephen K; Bellin, Melena D; Andersen, Dana K; Serrano, Jose; Yadav, Dhiraj; Pandol, Stephen J; Piomelli, Daniele. (2025). Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.. Cannabis and cannabinoid research, 10(1), 60-70. https://doi.org/10.1089/can.2024.0079
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