Cannabidiol (CBD), a major component of cannabis, has various effects such as antiemetic and anxiolytic activities, and it has recently been marketed as a supplement.The number of people using CBD during pregnancy is increasing, and there are concerns about its effects on the fetus. In addition, the scientific evidence supporting the fetal safety of CBD use during pregnancy is insufficient. To investigate CBD transfer from the mother to the fetus, a single intravenous dose of CBD was administered to pregnant mice in this study, and fetal pharmacokinetics (distribution and elimination) was analyzed. The transfer of CBD from the maternal blood to the fetus was rapid, and the compound accumulated in the fetal brain, liver, and gastrointestinal tract.Conversely, little CBD was transferred from the mother to the amniotic fluid. We analyzed the pharmacokinetics of CBD using a two-compartment model and found that the maternal and fetal half-lives of CBD were approximately 5 and 2 h, respectively. Furthermore, we performed a moment analysis of the pharmacokinetics of CBD, observing a mean residence time of less than 2 h in both the mother and fetus. These results suggest that once-daily CBD intake during pregnancy is unlikely to result in CBD accumulation in the mother or fetus.

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The capacity for metabolizing drugs that are substrates of CYP decreases during the active stage of ulcerative colitis but subsequently improves during the remission stage. This decrease in CYP expression was likely caused by the observed reduction in the levels of nuclearly localized pregnane X receptor and constitutive androstane receptor, and the increase in the production of inflammatory cytokines triggered by lipopolysaccharides.

The drug-metabolizing enzyme CYP is mainly involved in the metabolism of various substances in the liver, such as drugs, endogenous substances, and carcinogens. Recent reports have also revealed that CYP1B1 plays a major role in the developmental process. Because the level of CYP expression is markedly high in the liver, we hypothesize that CYP plays a role in the developmental process of the liver. To verify this hypothesis, we analyzed the expression patterns of various CYP molecular species and their functions during the differentiation of embryonic stem cells (ES cells) into hepatocytes and the developmental process in mice. The results demonstrated that CYP2R1 and CYP26A1 are expressed at an earlier stage of the differentiation of ES cells into hepatocytes than hepatoblast-specific markers. Additionally, during the development of the mouse liver, CYP2R1 and CYP26A1 were mostly up-regulated during the stage when hepatoblasts appeared. In addition, when CYP2R1 and CYP26A1 expressions were forced in ES cells and liver of adult mice, they differentiated into hepatoblast marker positive cells. These results suggest that CYP2R1 and CYP26A1 may play a major role in hepatoblast cell differentiation during the development of the liver.Key words embryonic stem cell; liver; CYP; hepatoblast The mature liver contains a variety of cell types, such as hepatocytes, sinusoidal endothelial cells, bile duct epithelial cells, stellate cells and Kupffer cells. The hepatocyte account for 80% of the volume of the liver and play a major role in liver functions, such as metabolism and excretion of drugs. Additionally, the fetal liver is known to act as a hematopoietic organ.The expression of CYP is significantly up-regulated in the liver, and CYP converts fat-soluble drugs into a water-soluble state so that they can be easily excreted. In addition to drug metabolism, CYP is also known to be involved in the oxidative metabolism of endogenous substances, including steroids, bile acid, hormones, and eicosanoids. To date, 58 types of CYP molecular species have been identified in humans, and 108 types have been identified in mice.1-3) As the CYP molecular species share high amino acid sequence homology in several substrate-recognition sites, in addition to the abovementioned functions of CYP, it may also play a major role in development and differentiation in the body. Because CYP begins to be expressed close to the time of hematopoiesis initiation during the fetal stage and CYP requires heme for its structure, CYP is considered to be involved in the development of the liver during the fetal stage. Moreover, it has been reported that the metabolites of endogenous substances and the intermediate metabolites of chemical substances have an effect on the development of individuals and on homeostasis.4-6) Therefore, CYP, which transiently appears during the process of development, is thought to possibly play an important role in the development of the liver.It has been reported that the knockout of either the CYP26A1 gene in mice causes abn...