NeuroImage
October 27, 2022
Anders Lykkebo-Valløe, Brice Ozenne, Sophia Armand et al.
44 citations
Psilocybin's acute perceptual psychedelic effects may arise from drug-level decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs. The authors apply and argue for a modified approach to modeling eigenvectors from LEiDA that more fully acknowledges their underlying structure. These findings contribute to a more comprehensive neurobiological framework underlying acute effects of serotonergic psychedelics.
medRxiv
July 3, 2023
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.
20 citations
preprint
Psychedelics like psilocybin are thought to increase brain entropy, but previous findings have not been replicated. In 28 healthy participants with 121 fMRI scans taken before and after psilocybin, brain entropy was measured alongside plasma psilocin levels, serotonin 2A receptor occupancy, and subjective drug intensity. Shannon entropy of path-length and instantaneous correlation distributions showed significant positive associations with drug effects, while sample entropy showed divergent associations depending on time-scale. However, 8 of 13 entropy metrics showed no significant effects, and the metrics correlated poorly with each other. The results suggest a nuanced acute effect of psilocybin on brain entropy and highlight specific metrics that may mediate clinical effects.
medRxiv
December 17, 2021
Anders S. Olsen, Anders Lykkebo-Valløe, Brice Ozenne et al.
4 citations
preprint
After a psychedelic dose of psilocybin, the occurrence and duration of two brain states involving lateral frontoparietal and medial fronto-parietal-cingulate coherence decrease, while a fully connected brain state increases. These changes are associated with both the level of psilocin in the blood and the intensity of the subjective drug experience. The findings suggest that the acute perceptual effects of psilocybin may arise from a shift away from specific frontoparietal connectivity motifs toward a more uniform connectivity structure. The study also proposes an improved method for modeling brain states from dynamic functional connectivity data.
medRxiv
January 16, 2026
Kristian Larsen, Patrick M Fisher, Drummond E. Mcculloch et al.
1 citation
Classical psychedelics such as LSD, psilocybin, and mescaline produce distinct changes in brain complexity and entropy that are not seen with stimulants like MDMA or d-Amphetamine. Using resting-state fMRI data from three placebo-controlled crossover trials with 79 participants across 255 sessions, the study found that psychedelics specifically increased meta-state complexity, short-timescale multiscale entropy, and dynamic conditional correlation entropy. Both drug classes increased Lempel-Ziv and spatial complexity and decreased absolute modularity, but only psychedelics showed these unique complexity and entropy increases. These findings suggest that psychedelic-specific brain signal changes may help distinguish the acute psychedelic state from other psychoactive drug effects and could be relevant to understanding their therapeutic potential.
Nature Communications
June 24, 2026
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.
A prominent theory holds that psychedelics increase brain entropy, but past studies have used many different entropy measures. This work analyzed 121 fMRI scans from 28 healthy adults before and after psilocybin, testing 14 entropy metrics with two brain-parcellation methods and seven denoising pipelines. Five metrics—including Shannon entropy of spatial eigendistribution, path-length, instantaneous correlations, brain-state switching, and sample entropy at short time-scales—consistently showed positive associations with psychedelic effects. However, eight metrics showed no significant effects, and Lempel-Ziv complexity gave inconsistent positive results. The entropy measures correlated poorly with each other, indicating that brain entropy is not a single, unified phenomenon.
bioRxiv
April 13, 2026
Anders S. Olsen, Kristian Larsen, Drummond E-W. McCulloch et al.
Psilocybin, a serotonergic drug, alters brain function and connectivity as measured with fMRI, but whether these effects are frequency-specific was unknown. In 28 healthy volunteers scanned after oral psilocybin (0.2–0.3 mg/kg), psilocin (the active metabolite) was associated with a selective reduction in low-frequency spectral power (0.01–0.06 Hz) and an increase in spectral entropy, with strongest effects in transmodal networks. Low-frequency connectivity energy explained by the unimodal/transmodal axis also decreased. These findings demonstrate that psilocin induces spatially distributed, frequency-dependent alterations, suggesting broadband fMRI analyses may obscure low-frequency dynamics and that frequency-resolved approaches offer greater sensitivity.