Abstract

Summary
Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti‐inflammatory effects. We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately. Colitis was induced in mice by 2,4‐dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC‐MS‐IT‐TOF). Endocannabinoids and related mediators were assessed by LC‐MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin‐1β, and intestinal permeability. CBG, but not CBD, given by oral gavage, ameliorated DNBS‐induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti‐inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon. By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease..