Maternal and Fetal Pharmacokinetic Analysis of Cannabidiol during Pregnancy in Mice

Abstract

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.

Pharmacokinetics of Cannabis and Its Derivatives in Animals and Humans During Pregnancy and Breastfeeding

“…Fetal THC concentrations in rats seem to be around 10% of the maternal concentrations 60 min after the administration of THC by gastric gavage, according to Hutchings et al ( Hutchings et al, 1989 ). Ochiai et al assessed the pharmacokinetics of CBD in maternal plasma, fetuses (whole body) and amniotic fluid of mice over a 24-hour period after an intravenous injection of 10 mg/kg of CBD ( Ochiai et al, 2021 ). The authors observed that CBD transfer to the fetus (whole body) began 15 min after CBD administration at a rate of 66.9%.…”

“…. (1985);Ginsburg et al (2014);Ochiai et al (2021) Brunet et al (2006;Itin et al (2020)Chiang et al (1983);Leuschner et al (1986);Mannila et al (2004);Mannila et al (2006); Al-Ghananeem et al (2011) Half-life (hours) Maternal and fetal: >10 Time of sampling 0-24 h after administration gastric gavage, according to Hutchings et al (Hutchings et al, 1989). Ochiai et al assessed the pharmacokinetics of CBD in maternal plasma, fetuses (whole body) and amniotic fluid of mice over a 24hour period after an intravenous injection of 10 mg/kg of CBD (Ochiai et al, 2021).…”

Animal Models Evaluating the Impact of Prenatal Exposure to Tobacco and Marijuana

“…NHP models have been integral in studying reproductive disorders 8. This review will largely focus on data generated from NHP and rodent models because of their respective translational implications and higher frequency of use for biomedical research, but will also briefly discuss other animal models that have also demonstrated significant prenatal effects following exposure to marijuana or its chemical components given that THC can readily cross the placenta and enter the fetal compartment 9,10…”

Metabolic Consequences of Gestational Cannabinoid Exposure

“…For CBD, established methods using meconium and umbilical cord samples from newborns for the detection of in utero cannabinoid exposure demonstrated that the range of CBD varies from 10-335 ng/mL [79]. In pregnant mice, 10 mg/kg (via tail vein injection) results in peak maternal serum concentrations of 2615.3 ± 442.3 ng/mL and peak fetal tissue concentrations of 598.7 ± 251.9 ng/g of fetus (whole body measurement) [80].…”