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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 使用不同的层析技术组合从大麻提取物中分离出24种化合物，包括真空液相色谱、开柱层析和高效液相色谱(正相和反相)。分离得到的化合物经UV、IR、GC-MS、HR-ESI-MS、一维和二维核磁共振确证结构。在鉴定的24种化合物中，有9种是首次从大麻中分离得到。这九种化合物包括四种羟化大麻素、环氧大麻酚酸、三种四氢大麻酸酯和一种四氢大麻酸醛。其余14种化合物为已知化合物，包括11种大麻素：脱氢大麻呋喃、大麻素、大麻环醇、大麻环酸、大麻酚、大麻酚酸、大麻酚酸、四氢大麻酚A、四氢大麻酚和大麻酚；3种非大麻素酚：大麻酚I、大麻环醇和大麻黄素B；以及一种甾醇：β-谷甾醇。所有分离的化合物都进行了CB1受体亲和分析(初步筛选)。只有4个化合物在测定中表现出高度抑制作用，与THC相当，1个化合物表现出中度抑制。这5种活性化合物均为羟化大麻类化合物，其中4种为新的天然产物。活性化合物的IC50分别为589 nm、624 nm、73 nm、1256 nm和6408 nm。对这些化合物进行了GTP？S测定，以确定它们是激动剂还是拮抗剂。

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.