Prenatal cannabidiol exposure alters physical and behavioral development in rats

Recently, it has been reported that 20% of pregnant women in the U.S. and Canada use cannabidiol (CBD) during pregnancy (Bhatia et al., 2024). The common perception is that CBD exposure is harmless to the fetus. However, the effects of CBD on the developing fetus are not well known, hampered by potential polydrug use, limited information on CBD levels in products, and varying drug administrative routes. Animal models may increase our understanding of the safety of CBD use during pregnancy. The current study exposed pregnant Sprague-Dawley rats to 50 mg/kg CBD or control vehicle once daily from gestational days 5-20. CBD was dissolved in honey and delivered via a cookie dough edible; controls received a cookie dough edible with no CBD. Exposure to CBD during gestation reduced the number of pups born and tended to increase the ratio of male-female pups by reducing the number of female pups, indicative of possible hormonal changes. Open field activity was examined in the offspring on postnatal days 30-34 (early adolescence) during the dark cycle. Prenatal CBD exposure significantly increased activity levels, impaired habituation, and increased risk-taking behavior in females, but not males. These data illustrate that prenatal CBD exposure may adversely impact behavioral development in a sex-dependent manner. Elucidation of the risks associated with CBD use during pregnancy is critical to inform pregnant women and promote healthy pregnancies.