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Psilocybin acutely reduces low-frequency BOLD power and frequency-specific connectivity

Anders S. Olsen, Kristian Larsen, Drummond E. Mcculloch, Melanie Ganz, Martin K Madsen, Brice Ozenne, Gitte M. Knudsen, Naveed Ur Rehman, Patrick M. Fisher

bioRxiv April 13, 2026 preprint DOI: 10.64898/2026.04.09.717379 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort
Sample size 28
Population Healthy volunteers
Intervention Psilocybin
Dose 0.2 – 0.3 mg/kg
Topics Psilocybin
Key findings Psilocybin produced 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.

Abstract

Abstract Psilocybin and other serotonergic drugs acutely alter human brain function and large-scale connectivity as measured with BOLD fMRI, but whether these effects are frequency-specific remains unknown. We applied multitaper spectral and cross-spectral analyses to resting-state fMRI data from 28 healthy volunteers scanned multiple times acutely following oral psilocybin administration (0.2 – 0.3 mg/kg), together with plasma psilocin measurements, to estimate psilocin associations with temporal frequency-specific activity and connectivity. Psilocybin produced a selective reduction in low-frequency spectral power (0.01 – 0.06 Hz ) and an increase in spectral entropy, with the strongest effects in transmodal networks. We also observed a reduction in low-frequency connectivity energy explained by the unimodal/transmodal axis. These findings demonstrate that psilocin induces spatially distributed, frequency-dependent alterations, suggesting that broadband fMRI analyses may obscure low-frequency dynamics. Frequency-resolved approaches may offer greater sensitivity for characterizing psychedelic effects on brain activity.

Comparable studies

Other observational and cohort studies on psilocybin, most cited first.

Study Year Design Participants
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression 2017 Observational cohort n = 19
Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers 2019 Observational cohort n = 8
Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans 2017 Observational study
Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) 2015 Observational cohort n = 190,000
Prediction of Psilocybin Response in Healthy Volunteers Healthy volunteers 2012 Observational cohort n = 409

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