Growing frustration with conventional therapeutic approaches to mental illness has prompted scientists to look toward serotonergic (or ‘classic’) psychedelics (LSD, psilocybin), given their potential for enhancing cognition and behavior and promoting personal growth and development. The psychedelic experience—described as ‘mystical’ or ‘spiritual’—is a primary driver of this research and preliminary findings over the past decade suggest that these psychoactive substances may be efficacious in treating psychiatric disorders including depression and post-traumatic stress disorder (PTSD). However, the mechanisms by which these psychedelics work in the brain are not well understood. As a result, research on serotonergic psychedelics is rapidly emerging as an important area of rodent translational research, in which experimental findings from rodents are translated to humans. Elucidating the mechanisms by which serotonergic psychedelics impact cognition and behavior is crucial for understanding their therapeutic potential. While animal models are fundamental to achieving this goal, translating findings from rodents to humans poses certain kinds of epistemic challenges. The aim of my project is to articulate these challenges and suggest potential avenues for overcoming them.