Jaipreet Mattu

In the last decade alone, a growing body of preliminary evidence suggests 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 translated to humans, 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. Our aim is to show that in addition to epistemic challenges that scientists face in translating findings from rodents to humans, there is also mismatch between experimental approaches used to investigate CPs in humans and rodents. We thus show current experimental practices are not conducive to mechanistic discovery. We end with a set of positive proposals to expedite the drive to translate CPs into effective treatments for depression. Keywords: classic psychedelics, psychiatry, clinical trials, collaboration, extrapolation, major depressive disorder, open science, philosophy of science, rodent models, scientific practice, translation, validity

Serotonergic (or “classic”) psychedelics have struck many researchers as raising significant philosophical questions that, until recently, were largely unexplored by academic philosophers. This paper provides an overview of four emerging lines of research at the intersection of academic philosophy and psychedelic science that have gained considerable traction in the last decade: selfless consciousness, psychedelic epistemology, psychedelic ethics, and spiritual/religious naturalism. In this paper, we highlight philosophical questions concerning (i) psychedelics, self-consciousness, and phenomenal consciousness, (ii) the epistemic profile of the psychedelic experience; (iii) ethical concerns about the appropriate use of psychedelics; and (iv) whether spiritual or religious dimensions of psychedelic use are compatible with a naturalistic worldview.