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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。大麻是已知的最古老的药用植物之一，也是大麻的来源，大麻是世界上使用最广泛的非法药物。到目前为止，已从大麻中分离和鉴定了近500种天然成分，其中研究最广泛的是β-9-四氢大麻酚(A9-THC)，它是目前公认的大麻属植物中的主要生物活性成分。A9-THC是大麻中主要的精神活性成分。它还被食品和药物管理局批准用于控制与化疗相关的恶心和呕吐，最近还被用于刺激患有消瘦综合征的艾滋病患者的食欲。该药物还显示出其他生物活性，可用于治疗青光眼、偏头痛、痉挛、焦虑和疼痛。A9-THC的作用机制涉及与内源性大麻素系统的相互作用。近年来，该系统已成为许多药物开发努力的焦点，以开发提供治疗益处的化合物，与A9-THC相比，滥用风险降低。鉴于大麻有数百种天然成分，我们假设大麻中许多特征不佳的成分也通过内源性大麻素系统显示出生物活性。我们预计其中一些将具有A9-THC样活性，另一些将增强A9-THC的活性，还有一些将成为A9-THC的天然拮抗剂。该项目将使用多学科方法来分离和分析以前从未被研究过生物活性的大麻的自然成分。该项目的具体目的是：1)分离和结构分析不同的大麻化合物，特别是生物活性未知的大麻三醇基和非大麻三醇类酚类化合物；2)确认分离出的化合物的作用机制涉及与内源性大麻素系统的相互作用；3)研究分离出的化合物的精神活性并将其与A9-THC进行比较；以及4)研究A9-THC与单独分离出的化合物的相互作用，并确定它们对大麻整体生物活性的贡献。预计这一项目的结果将提供有关大麻成分的重要新信息，这些成分有助于大麻的滥用责任和药用性能。

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. Cannabis sativa L. is the one the oldest plants known in medicine and also the source of marijuana, the most widely used illicit drug in the world. To date, a total of almost 500 natural constituents have been isolated and/or identified from Cannabis sativa L. The most widely studied has been delta-9-tetrahydrocannabinol (A9-THC), which is now recognized as the main biologically active component in the Cannabis plant. A9-THC is the primary psychoactive component in marijuana. It has also been approved by the Food and Drug Administration for the control of nausea and vomiting associated with chemotherapy, and more recently, for appetite stimulation of AIDS patients suffering from the wasting syndrome. The drug also shows other biological activities which lend itself to therapeutic applications for the treatment of glaucoma, migraines, spasticity, anxiety, and pain. The mechanism of action of A9-THC involves an interaction with the endogenous cannabinoid system. In recent years, this system has become the focus of many drug development efforts to develop compounds that provide therapeutic benefit, with a reduced abuse liability compared to A9-THC. Given that then; are hundreds of natural constituents of Cannabis, we hypothesize that many of the poorly characterized constituents in Cannabis also exhibit biological activity through the endogenous cannabinoid system. We anticipate that some of them will possess A9-THC-like activities, others will enhance the activity of A9-THC, and others will be natural antagonists of A9-THC. A multidisciplinary approach will be used in this project to isolate and analyze natural constituents of Cannabis that have never been studied before for biological activity. The specific aims of the project are to: 1) Isolate and structurally analyze different Cannabis compounds, especially cannabitriols group and non-cannabinoid phenolics, whose biological activity is unknown, 2) Confirm that the mechanism of action of the isolated compounds involves an interaction with the endogenous cannabinoid system, 3) Study the psychoactivtty of the isolated compounds and compare it with that of A9-THC, and 4) Study the interaction of A9-THC with the individual isolated compounds and determine their contribution to the overall biological activities of Cannabis. It is anticipated that the results of this project will provide important new information regarding the constituents of Cannabis that contribute to its abuse liability and medicinal properties.