Pharmaceutical Sciences Seminar
Faculty Candidate

Cody J. Wenthur, PharmD, PhD
Department of Chemistry
The Scripps Research Institute

Next-Generation Substance Use Disorder Therapeutics: Exploiting Complexity to Simplify Treatment

Despite the enormous health, social, and economic burdens that psychiatric illnesses have placed on the United States, the rate of entry into clinical trials for central nervous system (CNS) therapeutics is decreasing, as are the rates of success for those CNS compounds that do make it into human trials. This discrepancy is especially severe for substance use disorder (SUD), where overdose and dependence rates are rapidly increasing, yet few or no FDA-approved medications are available for treatment of these conditions. When addressing the challenges in developing new therapeutics for SUD, there is an opportunity to generate substantial benefit to the field by identifying common mechanisms that underlie the activity multiple classes of abused drugs. Furthermore, given the polypharmacologic nature of the mechanism of action for many drugs of abuse, there is also an opportunity to exploit multi-target psychoactivity within complex chemical mixtures arising from post-metabolic tissue samples or counterfeit drug products. The recent development of allosteric modulators directed toward metabotropic glutamate receptors provide a selective means to isolate individual receptors that support maladaptive learning behavior in addiction, while development of the DISSECTIV method provides a path to isolate contributions of single compounds and identify emergent behaviors arising from the concerted actions of synthetic psychoactive drug mixtures. Taken together, these two approaches present complementary routes to deconstruct complex biological and chemical systems in order to identify promising mechanisms for the development of next-generation means to treat substance use disorder.