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We’ve covered psychedelics on the podcast before—first in 2019 with Ira Byock, where we explored their potential role in medicine, and then again in 2023 with Stacy Fischer, Brian Anderson, and Theora Cimino, focusing on the reasons to approach psychedelic use in patients with caution. In today’s episode, we’re taking a closer look at the current state of the science around one specific psychedelic: psilocybin. We'll discuss three recent clinical trials involving patients with serious illness, joined by our guests James Downar, Ali John Zarrabi, and Margaret Ross. We begin with a refresher on psilocybin—what it is, how it might work, what conditions it may help treat (including demoralization), and how it’s typically administered. What makes this episode especially compelling is our deep dive into the three studies, which highlight two different approaches to using psilocybin: daily microdosing, similar to traditional antidepressants, and a more intensive model known as psilocybin-assisted therapy. This latter approach involves three structured phases—preparation, the dosing session, and post-session integration with trained therapists.