Psychopharmacology of plants and their metabolites used as marijuana substitutes

描述(申请人提供)：近年来，新的精神活性植物不断出现在街道上。一个例子是强致幻薄荷丹参及其活性代谢物salvinorin A。这种迷幻剂的使用不受联邦和大多数州法律的监管，正在全国和全球范围内蔓延。自1970年联邦政府颁布《管制物质法》成为法律，并将大麻(大麻)列入附表一以来，一些大麻替代品或替代品开始出现在市场上。这些植物很容易在许多互联网网站上获得，在不久的将来很有可能成为街头毒品。尽管它们现成可用，但这些植物及其代谢物的精神药理学在很大程度上是未知的。在大多数情况下，这些植物的活性成分和它们与中枢神经系统相互作用的机制都还没有确定。本项目的目的是研究用作大麻替代品的具有精神活性的植物的化学和药理学。对于这个项目，我们选择了五种具有突出网络销售报价的大麻替代品植物。我们建议根据北卡罗来纳大学教堂山分校的NIMH精神活性药物筛选计划，对这些植物的中枢神经系统受体电池进行生物学评估，并分离出对其精神作用负责的活性次生代谢物。从长远来看，该项目发现和开发的中枢神经系统受体的新配体将有助于更好地了解中枢神经系统的功能及其紊乱。为了实现这些目标，将实现以下具体目标：1.从流行的互联网来源和专业实体获得选定的植物物种。2.汽化/升华法鉴定活性代谢物3.生物物质的选择性提取4.提取物与中枢神经递质受体亲和力的生物学评价。5.生物测定引导的活性次生代谢物的分离和分离。6.分离代谢物的结构鉴定及其在特定受体系统中的生物再评价。该项目产生的数据将构成进一步研究的基础，并为寻求更广泛的资金提供初步结果。 公共卫生相关性：随着街道上精神活性植物和物质的数量不断增加，人们的健康，特别是年轻人的健康，成为一个越来越重要的问题。许多通过互联网宣传并用作大麻替代品的新兴致幻植物对此研究甚少。我们不知道它们在中枢神经系统中的作用机制，它们成为成瘾药物滥用的可能性，它们对人体重要器官和系统的毒性或其他副作用。我们研究用作大麻替代品的植物的精神药理学的项目将解决这些问题，并为这一领域的进一步研究提供信息。

DESCRIPTION (provided by applicant): In recent years, new psychoactive plants have been emerging on the streets. An example is the strong hallucinogenic mint Salvia divinorum and its active metabolite salvinorin A. The use of this hallucinogen, unregulated by Federal and most State laws, is spreading across the country and globe. Since 1970 when the Controlled Substances Act was enacted into law by Federal Government and cannabis (marijuana) was placed in the Schedule I, a number of marijuana substitutes or alternatives started to appear on the market. These plants are easily obtained on numerous internet sites and have a high potential of becoming street drugs in the near future. Despite their ready availability, the psychopharmacology of these plants and their metabolites is largely unknown. In most cases, neither the active constituents of these plants nor the mechanisms of their interactions with the central nervous system have been determined. The purpose of this project is the study of the chemistry and pharmacology of psychoactive plants used as marijuana substitutes. For this project, we have selected five marijuana-substitute plant species with prominent internet sales offers. We propose to biologically evaluate these plants against the battery of CNS receptors under the NIMH Psychoactive Drug Screening Program at the University of North Carolina at Chapel Hill, and isolate the active secondary metabolites responsible for their psychotropic effects. In the long-term, new ligands to CNS receptors discovered and developed in this project will contribute to better knowledge of the central nervous system functions and its disorders. To achieve these goals, the following specific aims will be pursued: 1. Acquisition of selected plant species from popular internet sources and professional entities. 2. Identification of active metabolites by vaporization/sublimation process 3. Selective extraction of biological material. 4. Biological evaluation of extracts for affinity to CNS neurotransmitters receptors. 5. Bioassay-guided fractionation and isolation of active secondary metabolites. 6. Structure elucidation of isolated metabolites and their biological re-evaluation in the specific receptor systems. The data generated by this project will form a basis for further research and provide preliminary results for seeking more extensive funding. PUBLIC HEALTH RELEVANCE: With the growing number of psychoactive plants and substances on the streets, concern for people's health, especially that of youth, becomes an increasingly important issue. Many of the emerging hallucinogenic plants advertised via Internet and used as marijuana substitutes are poorly studied. We do not know their mechanism of action in the central nervous system, their potential to become addictive drugs of abuse, their toxicity to vital organs and systems of the human body or other side effects. Our project to study the psychopharmacology of plants used as marijuana substitutes will address these issues and provide information to further research in this area.