Psychopharmacology of plants and their metabolites used as marijuana substitutes

描述（由申请人提供）：近年来，新的精神活性植物已经出现在街道上。一个例子是强烈的致幻薄荷鼠尾草（Salvia divinorum）及其活性代谢物鼠尾草素A。这种致幻剂的使用不受联邦和大多数州法律的管制，正在全国和地球仪蔓延。自1970年联邦政府颁布《管制物质法》成为法律，大麻（marijuana）被列入附表一以来，市场上开始出现一些大麻替代品或替代品。 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。尽管它们容易获得，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及其与中枢神经系统相互作用的机制都尚未确定。 该项目的目的是研究用作大麻替代品的精神活性植物的化学和药理学。在这个项目中，我们选择了五种具有突出互联网销售优惠的大麻替代植物。我们建议根据查佩尔山的北卡罗来纳州大学的NIMH精神活性药物筛选计划对这些植物的CNS受体电池进行生物学评价，并分离出负责其精神作用的活性次级代谢产物。从长远来看，本项目中发现和开发的新的CNS受体配体将有助于更好地了解中枢神经系统功能及其疾病。为实现这些目标，将努力实现以下具体目标：1.从流行的互联网资源和专业实体获取选定的植物物种。2.通过蒸发/升华工艺鉴别活性代谢物3.选择性提取生物材料。4.提取物对CNS神经递质受体亲和力的生物学评价。5.活性次级代谢产物的生物测定引导的分级分离。6.代谢产物的结构解析及其在特定受体系统中的生物学再评价。该项目产生的数据将成为进一步研究的基础，并为寻求更广泛的资金提供初步结果。 公共卫生相关性：随着街头精神活性植物和物质的数量不断增加，人们的健康，特别是青年人的健康，日益成为一个重要问题。许多新兴的致幻植物通过互联网广告，并用作大麻替代品的研究很少。我们不知道它们在中枢神经系统中的作用机制、它们成为滥用成瘾药物的潜力、它们对人体重要器官和系统的毒性或其他副作用。我们的项目，研究精神药理学的植物用作大麻替代品将解决这些问题，并提供信息，以进一步研究在这一领域。

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.