Psychedelics as Inspiration for Plasticity-Promoting Neurotherapeutics
Neural plasticity—broadly defined as the ability of the brain to change and adapt—is of fundamental importance to a properly functioning nervous system. It is the basis for learning and memory and enables our brains to recover from the pathological changes that underlie neuropsychiatric diseases such as depression, post-traumatic stress disorder, and substance use disorder. Recently, our group discovered that psychedelic natural products and related compounds, such as LSD, DMT, and ibogaine, rapidly promote structural and functional neural plasticity in rodents. These compounds are capable of re-wiring neural circuitry to produce long-lasting antidepressant, anxiolytic, and anti-addictive behavioral responses. Psychedelics have inspired our total synthesis and medicinal chemistry efforts to develop safer and more effective neurotherapeutics, and they serve as key chemical tools in our studies to understand the fundamental biochemical mechanisms that give rise to neural plasticity.