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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。的大麻是一种最古老的药用植物，也是世界上使用最广泛的非法药物大麻的来源。迄今为止，从大麻中已经分离和/或鉴定出近500种天然成分。研究最广泛的是δ-9-四氢大麻酚（A9-THC），它现在被认为是大麻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。它也已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，用于刺激患有消耗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，其适用于治疗青光眼、偏头痛、痉挛、焦虑和疼痛的治疗应用。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工作的重点，以开发提供治疗益处的化合物，与A9-THC相比，其滥用倾向降低。既然如此，是大麻的数百种天然成分，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表现出生物活性。我们预期它们中的一些将具有A9-THC样活性，其他将增强A9-THC的活性，并且其他将是A9-THC的天然拮抗剂。该项目将采用多学科方法分离和分析大麻的天然成分，这些成分以前从未被研究过生物活性。该项目的具体目标是：1）分离和结构分析不同的大麻化合物，特别是大麻三酚类和非大麻素酚类，其生物活性未知，2）确认分离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）研究分离的化合物的精神活性并将其与A9-THC的精神活性进行比较，和4）研究Δ 9-THC与单个分离的化合物的相互作用，并确定它们对大麻的总体生物活性的贡献。预计该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倾向和药用特性。

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.