The Effects of Maternal Delta-9-Tetrahydrocannabinol and Cannabidiol Exposure on Fetal Heart Development in Mice
Abstract
Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted in heart abnormalities in 73% of offspring with non-compaction of the myocardium and hypoplastic coronary arteries as the two main phenotypes. To our knowledge, this is the first reported study demonstrating that phytocannabinoids can induce congenital heart abnormalities. Cannabis consumption in human pregnancies could be teratogenic and should be avoided.