The Genetics of Cannabinoid Signaling: An Organismal Analysis

About This Grant

Summary Statement A 2024 publication in The Lancet Neurology by Dr. Steinmeĵ and collaborators of the Global Burden of Disease journal reviewed the prevalence of nervous system disorders worldwide from 1990-2021. Based on this comprehensive study, it was estimated that approximately 3 billion people worldwide suffered from neuropsychiatric and neurological disorders on a yearly basis during this time frame. From 2015-2018, adult usage of antidepressants in the United States increased from 10 to 13% (CDC National Center for Health Statistics, 2020). Patients suffering from depression and anxiety are traditionally prescribed selective serotonin reuptake inhibitors (SSRIs) and antipsychotic drugs. Recent clinical studies report that cannabidiol (CBD) also provides relief for these and other mental health disorders. However, the mechanisms of CBD action have yet to be completely resolved. The proposed research seeks to understand the molecular-genetic mechanisms of CBD action. From preliminary studies carried out by undergraduate research trainees and biology majors at Harris-Stowe State University Undergraduate (HSSU), we determined that Drosophila is a tractable and ideal model system to uncover conserved molecular-genetic mechanisms of CBD action within neuronal tissues. Drosophila neurotransmitzers (NTs) and their receptor targets are evolutionarily conserved across invertebrate and vertebrate species within tissues of the central and peripheral nervous systems. In addition to receptor- targeted regulation of neuronal responses, a population of noncanonical receptors, unique lipophilic membrane domains, and unknown targets modulate NT and CBD activity within vertebrates and invertebrates. Drosophila does not express CB1 and CB2 receptors, but larvae respond pharmacologically to CBD making this classical model system ideal for further investigation of offsite targets. We hypothesize that additional families of noncanonical CBD-responsive genes, especially those important for maintaining unique populations of phospholipids within membranes of brain tissues, function to regulate neural signaling pathways. These newly identified noncanonical genes will be genetically placed within cell signaling hierarchies to further understand the holistic mechanisms of CBD action. The proposed research will continue to support the mission of the HSSU Department of Life Sciences and College of STEM to place HSSU students into competitive professional training programs in medicine and science at the doctoral level towards boosting their success in the STEM workforce.