Chemistry and Pharmacology of Newly Emerging Psychoactive Plants

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DESCRIPTION (provided by applicant): In recent years new psychoactive plants and their active secondary metabolites have been emerging on the streets. An example is the strong hallucinogenic mint Salvia divinorum and its active metabolite salvinorin A. This use of new hallucinogens unregulated by Federal and most State laws is spreading across the country and globally. The 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 chemistry and pharmacology of these substances are largely unknown. In most cases neither the active constituents of these plants nor the mechanism of their interaction with the central nervous system have been determined. The purpose of this project is study the chemistry and pharmacology of lesser known emerging psychoactive plants with purported hallucinogenic or sedative activity. For this project we have selected 15 potent hallucinogenic/sedative plant species with little known chemistry and pharmacology. We propose to biologically evaluate these plants against the battery of CNS receptors under NIMH Psychoactive Drug Screening Program at the University of North Carolina at Chapel Hill and isolate the active secondary metabolites responsible for hallucinogenic and other 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 botanical gardens, private collections or commercial brokers. 2. Selective extraction of biological material. 3. Biological evaluation of extracts for affinity to CNS neurotransmitters receptors. 4. Bioassay-guided fractionation and isolation of active secondary metabolites. 5. Structure elucidation of isolated metabolites and their biological re-evaluation in the specific receptor systems. 6. Chemical transformations of lead compounds. 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 newly emerging hallucinogens on the streets, the concern of the health of people, especially youth, becomes a very important issue. For many hallucinogenic plants used we do not know their mechanism of action in central nervous system, their potential to become addictive drugs of abuse, their toxicity to vital organs and systems of human body or other side effects. Our project on the chemistry and pharmacology of newly emerging psychoactive plants will address these issues and provide information to further research in this area.