P 3: PSYCHOACTIVITY OF CANNABINOIDS & INTERACT W/ DELTA-9-TETRAHYDROCANNABINOL

P 3：大麻素的心理活性

• 批准号: 7610759
• 负责人: SAMIR A ROSS
• 金额: $ 20.09万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610759
• 关键词: Acids; Affinity; Agonist; Aldehydes; Biological Assay; Biological Factors; CNR1 gene; Cannabinoids; Cannabinol; Cannabis; Column Chromatography; Computer Retrieval of Information on Scientific Projects Database; Esters; Funding; Grant; High Pressure Liquid Chromatography; Institution; Liquid Chromatography; Phase; Research; Research Personnel; Resources; Source; Sterols; Structure; Techniques; Tetrahydrocannabinol; Time; United States National Institutes of Health; beta Sitosterol; cannabicyclol; cannabigerol; cannabigerolic acid; cannabinolic acid; cannabiripsol; cannabispiran; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Twenty four compounds have been isolated from Cannabis extracts using a combination of different chromatographic techniques, including vaccum liquid chromatography, open column chromatography, and HPLC (normal and reversed phase). The structures of the isolated compounds were established by UV, IR, GC-MS, HR-ESI-MS, 1D and 2D- NMR experiments. Nine out of the 24 identified compounds were isolated for the first time from Cannabis. These nine compounds include four hydroxylated cannabinoids, epoxycannabigerolic acid, three tetrahydrocannabinoic acid esters, and one THC aldehyde. The remaining 14 compounds are known and include 11 cannabinoids: dehydrocannabifuran, cannabicitran, cannabicyclol, cannabicyclolic acid, cannabigerol, cannabigerolic acid, cannabinol, cannabinolic acid, THC acid A, THC, and cannabiripsol; 3 non-cannabinoid phenolics: cannabispiran I, cannabispiranol, and canniflavin B; and one sterol: beta-sitosterol. All of the isolated compounds were subjected to CB1 receptor affinity assays (primary screen). Only four compounds showed highly significant inhibition in the assays, highly comparable with that of THC, and one showed moderate inhibition. The five active compounds are hydroxylated cannabinoids and four of them are new natural products. The IC50s of the active compounds are 589 nM, 624 nM, 73 nM, 1256 nM and 6408 nM. These compounds were subjected to GTP¿S assays in order to determine if they are agonists or antagonists.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 使用不同色谱技术的组合，包括真空液相色谱法、开放柱色谱法和HPLC（正相和反相），从大麻提取物中分离出24种化合物。化合物的结构经UV、IR、GC-MS、HR-ESI-MS、1D和2D-NMR确证。24种化合物中有9种是首次从大麻中分离得到的。这九种化合物包括四种羟基化大麻素、环氧大麻萜酸、三种四氢大麻酸酯和一种THC醛。其余14种化合物是已知的，包括11种大麻素：脱氢大麻呋喃、大麻西喃、大麻环醇、大麻环酸、大麻萜酚、大麻萜酸、大麻酚、大麻酚酸、THC酸A、THC和大麻酚; 3种非大麻素酚：大麻螺烷I、大麻螺烷醇和大麻黄素B;和一种甾醇：β-谷甾醇。 对所有分离的化合物进行CB 1受体亲和力测定（初步筛选）。只有四种化合物在测定中显示出高度显著的抑制作用，与THC的抑制作用高度相当，并且一种化合物显示出中度抑制作用。这五种活性化合物是羟基化的大麻素，其中四种是新的天然产物。活性化合物的IC 50分别为589 nM、624 nM、73 nM、1256 nM和6408 nM。对这些化合物进行GTP？S测定，以确定它们是激动剂还是拮抗剂。