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Making Sense with Sam Harris · May 29, 2026 · 30m

#478 — The Psychedelic Mind

Sam Harris speaks with Robin Carhart-Harris, a leading neuroscientist and psychedelic researcher. They discuss the current state of psychedelic science, including the FDA's recent denial of MDMA-assisted therapy for PTSD and the critical importance of set and setting. Carhart-Harris explains the REBUS model of how psychedelics relax the brain's high-level beliefs, the role of the default mode network in ego dissolution, and what microdosing research has (and hasn't) shown. The conversation also touches on the neuroscience of consciousness and the puzzling phenomenology of DMT entities.

This summary was generated from show notes and public descriptions, not from a full transcript review. Details may contain inaccuracies.

Canon

Set and Setting as Critical Determinants
The mindset (set) and physical/social environment (setting) are crucial for shaping the psychedelic experience and ensuring safety and therapeutic benefit.
Default Mode Network and Ego Dissolution
Psychedelics reliably decrease activity and connectivity in the default mode network, which correlates with the dissolution of the sense of self or ego.

Curious

REBUS Model of Psychedelic Action
The REBUS model (Relaxed Beliefs Under Psychedelics) proposes that psychedelics reduce the brain's reliance on prior beliefs, allowing a more unconstrained form of cognition.

Highlights

FDA Denial of MDMA-Assisted Therapy for PTSD
The FDA recently rejected an application to approve MDMA-assisted therapy for PTSD, a major setback for the field.
Risks for Vulnerable Populations
People with a personal or family history of psychosis face heightened risks from psychedelics, and screening is essential.
Mixed Evidence on Microdosing
Despite popular claims, rigorous studies on microdosing have so far failed to confirm large cognitive or mood benefits.
Psychedelics as Tools for Consciousness Research
Studying the brain under psychedelics provides a unique window into the neural correlates of conscious experience.
DMT Entities
Many users of DMT report encountering seemingly autonomous, intelligent entities, a phenomenon that remains scientifically unexplained.
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