Cannabidiol impairs neural tube closure in mouse whole embryo culture

BACKGROUND: Cannabidiol (CBD) is a nonpsychoactive constituent of cannabis widely available as a dietary supplement. Previous reports that it impairs the retinoid, sonic hedgehog, and folate metabolism pathways raise concern that it may impair closure of the embryonic neural tube (NT), producing NT defects including spina bifida and exencephaly. METHODS: We undertook teratogenicity testing of CBD in mouse whole embryo culture. RESULTS: At concentrations that do not diminish embryo viability, growth, or axial rotation, CBD dose‐dependently impairs cranial NT closure, increasing the proportion of embryos that develop exencephaly. It concomitantly diminishes closure of the spinal NT, the posterior neuropore (PNP), producing longer neuropores at the end of culture which is a hallmark of spina bifida risk. Exposure to CBD does not disrupt the formation of long F‐actin cables in surface ectoderm cells flanking the PNP or folding of the neuroepithelium at predictable hinge points. At the cellular level, CBD exposure does not alter proliferation or apoptosis of the spinal neuroepithelium. DISCUSSION: Thus, CBD acts selectively as a neuroteratogen predisposing to spina bifida and exencephaly in mouse whole embryo culture at exposure levels not associated with overt toxicity. Large‐scale testing of CBD's effects on NT closure, particularly in at‐risk groups, is warranted to inform its marketing to women of childbearing age.