Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain

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2 Scopus citations

Abstract

Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

Original languageEnglish
Pages (from-to)60-70
Number of pages11
JournalCannabis and Cannabinoid Research
Volume10
Issue number1
DOIs
StatePublished - Feb 1 2025

Bibliographical note

Publisher Copyright:
Copyright 2025, Mary Ann Liebert, Inc., publishers.

Funding

The authors thank the clinical research coordinators, laboratory staff and research personnel at the clinical centers, and staff at the Coordinating and Data Management Center for their contributions to the PROCEED study. The authors are grateful to their patients for their willingness to participate in the PROCEED study. This work was supported in part by Cedars-Sinai Cancer and by the National Cancer Institute (NCI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under award numbers: R21DK122293 and K01DK120737 (J.L.S.), U01DK108288 (S.S.V. and M.T.), U01DK108300 (W.G.P.), U01DK108306 (A.E.P. and D.Y.), U01DK108314 (S.J.P. and M.T.G.), U01DK108323 (E.L.F.), U01DK108326 (W.E.F.), U01DK108327 (P.A.H. and D.L.C.), U01DK108332 (S.K.V.), UO1DK108320 (C.E.F.), U01DK126300 (M.D.B.), and U01DK108328 (S.L., L.L., and Y.Y.). Additional support was provided by National Institute on Drug Abuse grant P50DA044118 (D.P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported in part by Cedars-Sinai Cancer and by the National Cancer Institute (NCI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under award numbers: R21DK122293 and K01DK120737 (J.L.S.), U01DK108288 (S.S.V. and M.T.), U01DK108300 (W.G.P.), U01DK108306 (A.E.P. and D.Y.), U01DK108314 (S.J.P. and M.T.G.), U01DK108323 (E.L.F.), U01DK108326 (W.E.F.), U01DK108327 (P.A.H. and D.L.C.), U01DK108332 (S.K.V.), UO1DK108320 (C.E.F.), U01DK126300 (M.D.B.), and U01DK108328 (S.L., L.L., and Y.Y.). Additional support was provided by National Institute on Drug Abuse grant P50DA044118 (D.P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

FundersFunder number
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute
Cedars-Sinai Cancer
National Institute of Diabetes and Digestive and Kidney DiseasesUO1DK108320, K01DK120737, U01DK108328, U01DK108306, U01DK108327, U01DK126300, U01DK108323, U01DK108326, U01DK108314, R21DK122293, U01DK108300, U01DK108288, U01DK108332
National Institute of Diabetes and Digestive and Kidney Diseases
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug AbuseP50DA044118
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse

    Keywords

    • cannabis
    • endocannabinoids
    • pain
    • pancreatitis

    ASJC Scopus subject areas

    • Pharmacology
    • Complementary and alternative medicine
    • Pharmacology (medical)

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