A cannabinoid analogue of Delta9-tetrahydrocannabinol disrupts neural development in chick.

Marijuana is the most commonly abused illicit drug by pregnant women. Its major psychoactive constituent, Delta(9)-THC (Delta(9)-tetrahydrocannabinol), crosses the placenta and accumulates in the foetus, 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 Delta(9)-THC on early embryogenesis. We have used the chick embryo as a model in order to characterize the effects of a water-soluble Delta(9)-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. (c) 2008 Wiley-Liss, Inc.