Drug Metab Dispos. 2021 Feb 2:DMD-AR-2020-000270. doi: 10.1124/dmd.120.000270. Online ahead of print.
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. Significance Statement CBD is currently marketed as a supplement, and despite its increasing use during pregnancy, little information concerning its fetal effects has been reported. In the present study, CBD was administered to pregnant mice, and the pharmacokinetics in the fetus was investigated using a two-compartment model and moment analysis. The results of these analyses provide important information for estimating the risk to the fetus if CBD is mistakenly consumed during pregnancy.