## 4 Discussion  
In recent years, the endocannabinoid system (ECS) has been receiving increased interest from researchers due to its potentially beneficial effects on the physiological processes underlying chronic pain, psychiatric disorders, epilepsy, autoimmune diseases, and cancer. Recent studies have shown that altering the endocannabinoid system influences inflammation and immune responses within the gut, similar to the disturbances in the endoopioid system. Therefore, the endocannabinoid system is a potential therapeutic target in patients suffering from inflammatory bowel diseases (IBDs) [28]. Studies on endogenous cannabinoids in inflammatory bowel diseases have been rare, and results and conclusions are sometimes conflicting. Some studies have focused on patients with IBDs and summarized data from CD and ulcerative colitis (UC) [29, 30]. Discrepancies may also result from the different types of samples, methods, and kits used for analysis, as well as the age of studied persons. Some researchers examined biopsies of inflamed intestinal tissue [29, 31], while others have measured endocannabinoid concentrations in the serum or plasma [30]. Figure 1: Comparison of AEA levels shown as mean and quartiles across three phases of [PERSON]’s disease: acute phase (CD1), during the treatment (CD2), remission (CD3), and in the control group. * means the statistically significant difference between the studied group and controls. ** indicates the probability at the border line of statistical significance, \(\Circle\) shows outliers. Figure 2: 2-AG concentrations in studied groups shown as median and quartiles in the acute phase (CD1), during the treatment (CD2), remission (CD3), and in the control group. \(\Circle\) shows outliers. The observed decrease in serum AEA levels which appeared in our study was also reported by [PERSON] et al., however, another study by [PERSON] et al. reported increased levels of AEA in patients with CD [28; 29]. There are different theories and proofs for the observed changes in endocannabinoid blood levels. [PERSON] et al. examined the mucosal activity of the enzymes responsible for AEA synthesis and degradation, NAPE-PLD and FAAH. These researchers concluded that the cause of lowered AEA levels was decreased activity of NAPE-PLD and increased activity of FAAH. [PERSON] et al. found an increase in both AEA and 2-AG levels in adults with CD by testing the eCB plasma levels [29]. The authors concluded that the decreased CB1 gene expression, which is the primary receptor for AEA, is the reason. The disparity in the results between studies should be an indication of the need for further research into the characteristics of AEA. The lack of changes in the concentration of 2-AG, a representative of endocannabinoids in the course of CD, is puzzling. Similar observations were noted by [PERSON] et al., with no statistically significant differences found between the control group and the group of patients with CD and UC in the concentration of 2-AG in the intestinal mucosa obtained during a biopsy or surgery in adults [28]. The researchers suggest that the real expression of 2-AG could be increased in IBD patients but is masked by an increased level of the enzymes responsible for the degradation of endocannabinoids, FAAH and MAGL. The other explanation is the decreased activity of NAPE-PLD. In 2004, [PERSON] et al. showed that CB1-deficient mice had more intensive inflammation during induced colitis than normal mice; the same results were observed when the CB1 receptor was pharmacologically blocked. Moreover, administration of cannabinoid receptor agonist resulted in protection against induced colitis in FAAH-deficient and wild mice [31]. It was noted that the administered cannabinoid receptor agonist also targeted other metabolic pathways, resulting in an anti-inflammatory mechanism. Nevertheless, the CB1 receptor plays a major role in the prevention of intestinal inflammation, based on observations in CB1-deficient mice.