Developing Cannabinoid Molecular Derivatives in Diagnostics and Therapeutics for Bipolar Disorder.
The purpose of this proposed collaborative, interdisciplinary (chemistry and molecular biology) research project is systematic design and development of novel cannabinoid hybrids as probes and treatment for bipolar disorder (BD). This proposal builds upon an ongoing research collaboration between PIs Marlene Murray and Desmond Murray engaging undergraduate students in novel synthesis and bioactivity of hybrid psychotropic compounds as potential anti-bipolar disorder agents. Specifically, this proposal is based on (a) Dr. Marlene Murray’s ongoing interest, molecular biology research, and discoveries in bipolar disorder and in monitoring inositol levels in response to potential anti-bipolar agents in yeast and mammalian cell models, and (b) the development of synthetic methodology for creating biologically relevant hybrid molecules, such as, acylals, amides and acylureas, in the laboratory of Dr. Desmond Murray. The current literature indicates (1) an over-50 year decline in psychiatric drug development in the pharmaceutical industry which has created an urgent need for new and better psychotropic diagnostics and therapeutics, in general, and for bipolar disorder, in particular, (2) the need to develop new safer psychotropic drugs, including BD drugs, with fewer, less harmful, less unmanageable side effects, (3) the discovery of new biomolecular targets for psychiatric disorders, (4) some signs of increasing researcher interest in the field of psychiatric drug discovery, (5) the growing research and advances in the field of small molecule hybrid drug medicinal chemistry, and (6) an increasing body of reliable studies and reports regarding the psychotropic effects of cannabinoids. So, our proposed project lies at the cutting edge and intersection of multiple needs and fields and continues to provide us opportunities for pedagogical instruction and research for Andrews University undergraduate students, particularly from, but not limited to, our biology and chemistry departments. Development of our proposed novel hybrid cannabinoids employs established organic synthetic methodology. As far as we know, our proposed cannabinoid, CBD and CBG hybrids have not been made and or studied in general or specifically as therapeutics for psychotropic diseases including BD. Furthermore, the synthetic methodology facilitates rapid access to a wide diversity of molecules to investigate the structure – bioactivity relationships of our proposed cannabinoid hybrids.