## 4 Discussion
As AEA is a potent CB1 agonist, it is possible that the decrease in its serum concentration results in reduced anti-inflammatory activity on GI mucosa, thus resulting in more pronounced CD symptoms, and in patients in remission, facilitating recurrence of the disease. [PERSON] et al. found the AEA concentration to be lower in IBD inflamed mucosa in comparison to IBD uninflamed mucosa, which implies some kind of self-reinforcing dysregulation inflammatory processes related to the EC system. Interestingly, the same study also found the CB1 receptor expression to be higher in the inflamed mucosa, which might be some kind of compensation for a lower concentration of AEA [28]. On the other hand, cannabinoids have also the ability to regulate intestinal motility by reducing smooth muscle contractility [32] and the rate of gastric emptying. This slowing of motility may be one of the factors behind some reports on the effectiveness of cannabis in reducing diarrhea, though such reports mostly rely on patient-reported outcomes. The positive effect of cannabinoids (exo- and endogenous) in the course of CD also includes the stimulating effect on the appetite center, which is especially important in the period of remission [32; 33]. It is estimated that 65 to 75% of CD patients suffer from malnutrition. Depending on the severity of the course of CD and the duration of the disease, secondary symptoms associated with the malabsorption syndrome may appear, such as electrolyte disturbances, anemia, avitaminosis, especially B12, and hypoproteinemia. In pediatric patients, malnutrition is the main cause of growth retardation [34; 35]. Additionally, a decrease in bone mineral density is often noticed in CD patients, which may be related to the frequent vitamin D3 deficiency [36]. According to a study by [PERSON] et al., patients with IBD who used cannabis reported significant improvement in various self-assessed symptoms, such abdominal pain, abdominal cramping, diarrhea, and joint pain. Interestingly, the same study also found a correlation between long-term cannabis use and the necessity for surgery in patients with CD, but as the authors noted, it may be because people who used cannabis for their symptoms had greater disease severity [37; 38]. The diminished long-termconcentration of AEA deteriorates all these above-mentioned symptoms and deficiencies, worsening the course of the disease and prolonging the duration of the disease. There are various approaches that can enhance endocannabinoid-related signaling: increasing eCB production and secretion, administration of exogenic eCB analogs, and inhibiting the enzymes responsible for the degradation of eCBs. So far, the most extensively examined was the third approach. To date, there are a few studies on humans describing the effects of FAA inhibitors on various diseases, but none regarding their use in treating IBD. Animal studies revealed the mechanism of action of FAAH and/or MAGL inhibitors. [PERSON] et al. have shown that total FAAH inhibition combined with partial inhibition of MAGL (using PF-3845 combined with JZL184) in mice has a strong antinociceptive effect without significant cannabimimetic side effects; additionally, the measured brain AEA levels increased more than 10 times, while 2-AG levels increased 2-3 times [39]. A similar study, using only MAGL inhibitor JZL184, also by [PERSON] et al., showed a reduction of mechanical allodynia and paw edema in the carrageenan test in mice [40]. In a study by [PERSON] et al., FAAH inhibitor PF-3845 administered to two mouse models of colitis (TNBS-induced and DSS-induced) provided an anti-inflammatory effect measured by both microscopic and biochemical findings in the TNBS-induced colitis model, but it had no positive effect on DSS-induced colitis [41]. As previously stated, reduced activity of the FAAH enzyme, which is responsible for breaking down AEA, is responsible for the increased concentration of AEA which has anti-inflammatory properties.