Classic psychedelics in translational research: addressing epistemic challenges from bench to bedside

Abstract

Abstract In the last decade alone, preliminary evidence has suggested that classic psychedelics (CPs) can rapidly and durably ameliorate symptoms and cognitive deficits associated with depression. However, the mechanisms by which CPs work in the brain are not well understood. Rodent translational research, in which experimental findings from rodents are used to understand the human brain, is fundamental in achieving this goal. This chapter focuses on a representative subset of human and rodent studies investigating CPs for depression, including the various lines of research that have been initiated to understand how they work. It is shown that in addition to epistemic challenges that scientists face in translating findings from rodents to humans, there is a mismatch between experimental approaches used in human clinical trials and rodent translational studies. Thus, current experimental practices are not conducive to mechanistic discovery. The chapter concludes with a set of positive proposals to expedite the drive to translate CPs into effective treatments for depression.