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

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.

Keywords: cannabis; endocannabinoids; pain; pancreatitis.

FIG. 1.

Hypothetical role of the endocannabinoid system in pain control among individuals with pancreatitis.

FIG. 2.

Adjusted median endocannaboid levels by pancreatic disease status. All analyses performed by generalized linear regression modeling on log-transformed data and adjusted for processing time (log-transformed). AEA was additionally adjusted for sex. PEA was additionally adjusted for BMI group. CAP: Chronic abdominal pain of suspected pancreatic origin and indeterminate chronic pancreatitis; AP: Acute pancreatitis; RAP: Recurrent acute pancreatitis; CP: Chronic pancreatitis * p = 0.047

FIG. 3.

Serum endocannabinoid levels by pain type and PROMIS pain scores. (A) By pain type. (B) By abdominal pain reported in past year. (C) By abdominal pain reported in past week. (D) By most severe pain reported in past week. (E) PROMIS Pain Interference Scale (T-score). (F). PROMIS Pain Intensity Scale (0–10). PROMIS, Patient-Reported Outcomes Measurement Information System. All analyses performed by generalized linear regression modeling on log-transformed data and adjusted for processing time (log-transformed) and disease group. AEA was additionally adjusted for sex. PEA was additionally adjusted for BMI group. Cases: Chronic abdominal pain of suspected pancreatic origin and indeterminate chronic pancreatitis; Acute pancreatitis; Recurrent acute pancreatitis; Chronic pancreatitis.