Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA; Center on Human Development and Disability, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, University of Washington, Seattle, WA, USA.
Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
Pharmacol Ther. 2018 Feb;182:133-151. doi: 10.1016/j.pharmthera.2017.08.014. Epub 2017 Aug 25.
The broad-based legalization of cannabis use has created a strong need to understand its impact on human health and behavior. The risks that may be associated with cannabis use, particularly for sensitive subgroups such as pregnant women, are difficult to define because of a paucity of dose-response data and the recent increase in cannabis potency. Although there is a large body of evidence detailing the mode of action of Δ-tetrahydrocannabinol (THC) in adults, little work has focused on understanding how cannabis use during pregnancy may impact the development of the fetal nervous system and whether additional plant-derived cannabinoids might participate. This manuscript presents an overview of the historical and contemporary literature focused on the mode of action of THC in the developing brain, comparative pharmacokinetics in both pregnant and nonpregnant model systems and neurodevelopmental outcomes in exposed offspring. Despite growing public health significance, pharmacokinetic studies of THC have focused on nonpregnant adult subjects and there are few published reports on disposition parameters during pregnancy. Data from preclinical species show that THC readily crosses the placenta although fetal exposures appear lower than maternal exposures. The neurodevelopmental data in humans and animals suggest that prenatal exposure to THC may lead to subtle, persistent changes in targeted aspects of higher-level cognition and psychological well-being. There is an urgent need for well-controlled studies in humans and preclinical models on THC as a developmental neurotoxicant. Until more information is available, pregnant women should not assume that using cannabis during pregnancy is safe.
大麻使用的广泛合法化,使得人们强烈需要了解其对人类健康和行为的影响。由于缺乏剂量反应数据和大麻效力的最近增加,与大麻使用相关的风险(特别是对于孕妇等敏感亚组)难以定义。尽管有大量证据详细说明了 Δ-四氢大麻酚(THC)在成人中的作用模式,但很少有工作专注于了解怀孕期间使用大麻如何可能影响胎儿神经系统的发育,以及是否可能有其他植物衍生的大麻素参与其中。本文概述了重点关注 THC 在发育中的大脑中的作用模式、在怀孕和非怀孕模型系统中的比较药代动力学以及暴露后代的神经发育结果的历史和当代文献。尽管公共卫生意义日益重要,但关于 THC 的药代动力学研究主要集中在非怀孕的成年受试者上,怀孕期间的处置参数发表的报告很少。来自临床前物种的数据表明,尽管胎儿暴露似乎低于母体暴露,但 THC 很容易穿过胎盘。人类和动物的神经发育数据表明,产前暴露于 THC 可能导致针对更高水平认知和心理健康的特定方面的微妙、持久的变化。迫切需要在人类和临床前模型中对 THC 作为发育神经毒物进行良好控制的研究。在有更多信息之前,孕妇不应认为在怀孕期间使用大麻是安全的。