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

Olsen ASiD, Larsen K, McCulloch DEiD, Ganz M, Madsen MK, Ozenne BiD, Knudsen GM, Rehman NuiD, Fisher PM

Apr 13, 20260 citationsDOI: 10.64898/2026.04.09.717379

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.

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Psilocybin

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