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Neural correlates of insight on psilocybin: a within-subjects, healthy volunteer study

Poster Session F - Tuesday, March 10, 2026, 8:00 – 10:00 am PDT, Fairview/Kitsilano Ballroom

Lorenzo Pasquini¹ (), Manesh Girn¹, Hannes Kettner¹, Avery Ostrand¹, Kate Allison¹, Christian Valtierra¹, Will Lucas¹, Patrick McConnell¹, Catriona Miller¹, Sydney Griffith¹, Dawn Weinstein¹, Brian Anderson¹, Andrea Rosati¹, Jennifer Mitchell¹, Robin Carhart-Harris¹; ¹University of California San Francisco

Psilocybin is a serotonergic psychedelic that induces altered states of consciousness characterized by profound psychological insights, which can catalyze powerful therapeutic breakthroughs for a range of psychiatric conditions. However, the neuronal signatures of different psychedelic substates that arise within a dosing session, as well as across sessions and individuals, have not been fully characterized. To address this gap, we conducted a personalized neuroimaging study in healthy, psychedelic-experienced volunteers. 10 participants were dosed with up to 25 mg psilocybin on four distinct dosing days, with each dosing day separated by the next by at least one week. On each dosing day, we measured participants’ brain activity multiple times using fMRI, with three runs being collected before dosing as well as at 50-, 120-, and 190-min post-dosing. Each scan session was followed by a brief resting-state EEG session. Normalized global signal complexity – NGSC, an index of the unpredictability of brain activity – initially increased at 50 min post-dose, peaked at 120 min post-dose, and gradually decreased at 190 min-postdose when compared to the pre-dose scans. NGSC increases were particularly prominent among medial parietal and prefrontal brain areas overlapping with the default mode network. NGSC correlated with EEG-based increases in signal complexity assessed via Lempel Ziv Complexity as well as with self-reported levels of psychological insight, assessed through visual analog scales after each fMRI run. Our findings show that personalized approaches applied to neuropharmacological studies have the potential to elucidate the dynamics of psychedelic substances on both brain function and individual experience.

Topic Area: EMOTION & SOCIAL: Emotion-cognition interactions