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
Prevention and Control Program, Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California, USA..
Department and Anatomy and Neurobiology, University of California, Irvine, California, USA.
Cannabis Cannabinoid Res. 2025 Feb;10(1):60-70. doi: 10.1089/can.2024.0079. Epub 2024 Sep 18.
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). A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease ( = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) ( = 22), acute pancreatitis ( = 33), recurrent acute pancreatitis ( = 57), and definite CP ( = 63). Circulating AEA concentrations were higher in women than in men ( = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight ( = 0.003). Asymptomatic controls with no pancreatic disease had significantly ( = 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 ( = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower ( = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. 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.
本研究调查了胰腺炎及胰腺炎相关疼痛与两种内源性大麻素分子(如花生四烯酸乙醇胺(AEA)和2-花生四烯酸甘油酯(2-AG))以及两种类大麻素分子(如油酰乙醇胺(OEA)和棕榈酰乙醇胺(PEA))血清水平之间的关联。在慢性胰腺炎的前瞻性流行病学和转化研究评估中进行了一项病例对照研究,研究对象包括无胰腺疾病者(n = 56)、疑似胰腺起源的慢性腹痛或不确定的慢性胰腺炎(CP)患者(n = 22)、急性胰腺炎患者(n = 33)、复发性急性胰腺炎患者(n = 57)以及确诊的CP患者(n = 63)。女性循环AEA浓度高于男性(P = 0.0499),肥胖参与者的PEA浓度高于体重过轻/正常或超重者(P = 0.003)。与所有疾病组合并相比,无胰腺疾病的无症状对照者的AEA浓度显著较低(P = 0.03)。AEA浓度最高的是急性胰腺炎患者,其次是复发性急性胰腺炎患者、慢性腹痛/不确定CP患者和确诊的CP患者。在过去一年中报告有腹痛的胰腺炎患者的AEA浓度显著高于无症状对照者(P = 0.04)。在过去一周内报告有腹痛的参与者中,2-AG水平显著较低(P = 0.02),且疼痛强度与2-AG和OEA浓度呈负相关。内源性大麻素水平可能与胰腺炎的阶段有关,或许是通过激活CB1受体。对我们研究结果的验证将支持在该患者群体中对新型治疗方法进行研究,包括大麻素受体-1拮抗剂。