Studies of Cannabidiol in Neurodevelopment

大麻二酚在神经发育中的研究

基本信息

  • 批准号:
    10366030
  • 负责人:
  • 金额:
    $ 19.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-04-01 至 2024-03-31
  • 项目状态:
    已结题

项目摘要

Cannabidiol (CBD) is a terpenoid constituent of the cannabis plant that is currently enjoying popularity as an herbal and food additive with purported beneficial effects in the treatment of anxiety, sleep disorders, inflammation and pain. Epidemiological studies indicate that use of CBD-containing products is increasing, including among pregnant and lactating women. In spite of these trends, we know very little about the effects of CBD on the developing brain. The purpose of the studies in this exploratory project is to examine the consequences of CBD exposure during development on the functioning of the cerebellum in later life. The overall hypothesis of these studies is that exposure of developing neurons to CBD results in increased apoptosis and dysregulated outgrowth of axons and dendrites. The specific goals of this project are to explore this hypothesis in the cerebellum of mice. The premise of this project is supported by a few studies in the literature and by preliminary data from our laboratory demonstrating that CBD exposure in utero results in significant reductions in performance on the rotarod assay, indicative of loss of balance and coordination. In addition, we have found that direct exposure of cerebellar granule neurons (CGNs) in culture to CBD results in apoptosis and, at lower concentrations, inappropriate activation of glycogen synthase kinase 3ß (GSK3ß). GSK3ß regulates activity-dependent dendritic arborization in CGNs and its over-activation has been associated with loss of appropriate cell morphology and connections to targets. Thus, our preliminary data support the hypothesis that CBD can be neurotoxic to developing neurons in the cerebellum. A second goal of these studies is to explore the hypothesis that GPR55, a G protein coupled receptor that is antagonized by CBD, is the site of action for CBD to affect neuronal development. In the first aim, we will examine the effects of perinatal CBD exposure on several cerebellar-dependent behaviors and cerebellar morphology at several ages. We will study the hypothesis that GPR55 is the site of action of CBD to alter cerebellar function and determine whether GSK3ß phosphorylation is altered by in vivo exposure to CBD. We utilize a voluntary consumption method for the administration of CBD to pregnant mice and will measure the concentrations of CBD that result in the dam and pups using this approach. In the second aim, we will examine the mechanism by which CBD affects GSK3ß activity in cultured CGNs, focusing on the role of GPR55, and determine the effects of CBD on activity-dependent neuritic outgrowth in these neurons. Successful completion of these studies will provide important information regarding the role of CBD in neuronal maturation and will begin to address an important gap in our knowledge regarding the effects of perinatal CBD exposure on brain development.
大麻二酚(CBD)是大麻植物的萜类成分,目前作为一种药物受到欢迎

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)

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Cecilia J Hillard其他文献

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?
循环内源性大麻素:它们来自何处以及去向何方?
  • DOI:
    10.1038/npp.2017.130
  • 发表时间:
    2017-06-27
  • 期刊:
  • 影响因子:
    7.100
  • 作者:
    Cecilia J Hillard
  • 通讯作者:
    Cecilia J Hillard

Cecilia J Hillard的其他文献

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{{ truncateString('Cecilia J Hillard', 18)}}的其他基金

2023 Cannabinoid Function in the CNS Gordon Research Conference and Gordon Research Seminar
2023中枢神经系统戈登研究会议和戈登研究研讨会大麻素功能
  • 批准号:
    10683605
  • 财政年份:
    2023
  • 资助金额:
    $ 19.5万
  • 项目类别:
Mechanisms underlying the influence of stress on drug-seeking behavior
压力对药物寻求行为影响的机制
  • 批准号:
    10752220
  • 财政年份:
    2023
  • 资助金额:
    $ 19.5万
  • 项目类别:
Examining the impact of circulating endocannabinoid levels on neurocognition, mood, and early cannabis use in youth enrolled in the ABCD Study
检查循环内源性大麻素水平对参加 ABCD 研究的青少年的神经认知、情绪和早期大麻使用的影响
  • 批准号:
    9916212
  • 财政年份:
    2019
  • 资助金额:
    $ 19.5万
  • 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
  • 批准号:
    10477473
  • 财政年份:
    2019
  • 资助金额:
    $ 19.5万
  • 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
  • 批准号:
    10238098
  • 财政年份:
    2019
  • 资助金额:
    $ 19.5万
  • 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
  • 批准号:
    10013295
  • 财政年份:
    2019
  • 资助金额:
    $ 19.5万
  • 项目类别:
Examining the impact of circulating endocannabinoid levels on neurocognition, mood, and early cannabis use in youth enrolled in the ABCD Study
检查循环内源性大麻素水平对参加 ABCD 研究的青少年的神经认知、情绪和早期大麻使用的影响
  • 批准号:
    10019508
  • 财政年份:
    2019
  • 资助金额:
    $ 19.5万
  • 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
  • 批准号:
    10689093
  • 财政年份:
    2019
  • 资助金额:
    $ 19.5万
  • 项目类别:
Circulating endocannabinoids in rats: Assay development and validation
大鼠循环内源性大麻素:检测方法开发和验证
  • 批准号:
    9306814
  • 财政年份:
    2016
  • 资助金额:
    $ 19.5万
  • 项目类别:
CB2 Cannabinoid Receptors and Cocaine Action: Studies with Conditional Knock Outs
CB2 大麻素受体和可卡因作用:条件敲除研究
  • 批准号:
    9250114
  • 财政年份:
    2016
  • 资助金额:
    $ 19.5万
  • 项目类别:

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