A cannabinoid analogue of Δ9‐tetrahydrocannabinol disrupts neural development in chick

Marijuana is the most commonly abused illicit drug by pregnant women. Its major psychoactive constituent, Δ⁹‐THC (Δ⁹‐tetrahydrocannabinol), crosses the placenta and accumulates in the f?tus, potentially harming its development. In humans, marijuana use in early pregnancy is associated with miscarriage, a fetal alcohol‐like syndrome, as well as learning disabilities, memory impairment, and ADHD in the offspring. Classical studies in the 1970 s have reached disparate conclusions as to the teratogenic effects of cannabinoids in animal models. Further, there is very little known about the immediate effects of Δ⁹‐THC on early embryogenesis. We have used the chick embryo as a model in order to characterize the effects of a water‐soluble Δ⁹‐THC analogue, O‐2545, on early development. Embryos were exposed to the drug (0.035 to 0.35 mg/ml) at gastrulation and assessed for morphological defects at stages equivalent to 9–14 somites. We report that O‐2545 impairs the formation of brain, heart, somite, and spinal cord primordia. Shorter incubation times following exposure to the drug show that O‐2545 interferes with the initial steps of head process and neural plate formation. Our results indicate that the administration of the cannabinoid O‐2545 during early embryogenesis results in embryotoxic effects and serves to illuminate the risks of marijuana exposure during the second week of pregnancy, a time point at which most women are unaware of their pregnancies. Birth Defects Res (Part B) 83:477–488, 2008. © 2008 Wiley‐Liss, Inc.