Teratogenic Effects of Marijuana in Developing Chick CNS

描述（由申请人提供）：该提案的目的是评估大麻对发育中的神经系统的致畸作用。大麻是孕妇最常用的非法药物。大麻的主要精神活性成分四氢大麻酚（THC）会穿过胎盘，在胎儿大脑中积累，可能会损害中枢神经系统的发育。在怀孕早期吸食大麻会导致流产和后代在10岁时出现认知异常，比如智商低、学习障碍、记忆障碍和多动症。动物模型显示，四氢大麻酚暴露在相当于人类怀孕两到三周的时期，会导致发育中的神经系统畸形。在这个时候，大多数女性都不知道自己怀孕了，因此也不知道大麻的潜在有害影响。我们建议结合显微外科，药理学和分子方法，以小鸡为动物模型，表征大麻对大脑发育初始阶段的胚胎毒性作用。这项研究将为更好地了解怀孕早期接触大麻的风险提供信息，并将为涉及其他滥用药物（如酒精、可卡因、甲基苯丙胺和阿片类药物或其组合）的致畸性研究提供基础。

DESCRIPTION (provided by applicant): The goal of the proposal is to assess the teratogenic effects of marijuana on the developing nervous system. Marijuana is the most commonly used illicit drug by pregnant women. Its major psychoactive constituent, THC, crosses the placenta and accumulates in fetal brain, potentially harming CNS development, marijuana use in early pregnancy is associated with miscarriage and cognitive abnormalities at age 10 in the offspring, such as lower IQ and learning disabilities, memory impairment and ADHD. Animal models show that THC exposure at a period corresponding to weeks two-three of human pregnancy, results in teratogenesis of the developing nervous system. At this time point, most women are unaware of their pregnancy, and thus of the potentially harmful effects of marijuana. We propose to use a combination of microsurgical, pharmacological and molecular approaches using chick as an animal model, to characterize the embryotoxic effects of marijuana on the initial steps of brain development. This research will provide information for a better understanding of the risks of marijuana exposure during early pregnancy, and will serve as a basis for teratogenic studies involving other drugs of abuse, such as alcohol, cocaine, metamphetamine and opiates, or combinations thereof.