Jacqueline Anne Sullivan

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

Ian Hacking instigated a revolution in 20th century philosophy of science by putting experiments (“interventions”) at the top of a philosophical agenda that historically had focused nearly exclusively on representations (“theories”). In this paper, I focus on a set of conceptual tools Hacking (1992) put forward to understand how laboratory sciences become stable and to explain what such stability meant for the prospects of unity of science and kind discovery in experimental science. I first use Hacking’s tools to understand sources of instability and disunity in rodent behavioral neuroscience. I then use them to understand recent grass-roots collaborative open science initiatives aimed at establishing stability in this research area and tease out some implications for unity of science and kind creation and discovery in cognitive neuroscience.