Study finds single dose of psilocybin causes measurable brain changes in first-time users

May 5, 2026

A Nature Communications study demonstrates that a single 25mg dose of psilocybin produces both immediate and lasting brain changes in 28 healthy first-time users. EEG recordings showed acute increases in brain entropy and gamma power with decreased alpha and theta power at 1-2 hours post-dosing, coinciding with peak subjective intensity. One month later, DTI scans revealed decreased axial diffusivity in prefrontal cortex-striatum and prefrontal cortex-thalamus tracts, alongside reduced brain network modularity that correlated with improved well-being. A control dose of 1mg psilocybin produced no measurable changes, strengthening causal attribution to the higher dose and suggesting psilocybin induces enduring neuroplastic effects.

Acute brain changes during psilocybin administration

▪Significant decreases in alpha power were observed after 25 mg psilocybin administration.
▪Significant increases in Lempel-Ziv complexity (LZc), a measure of informational entropy of spontaneous scalp potentials, were observed at 1 and 2 hours after 25 mg psilocybin administration.
▪Eyes-closed, task-free electroencephalography (EEG) recordings were done in healthy human volunteers during psilocybin administration at 1, 2, and 4.5 hours post-dosing.
▪Power increases in the gamma band at 2 hours and decreases in the theta band at 1 and 2 hours were observed after 25 mg psilocybin administration.
▪Increases in brain entropy (LZc) and decreases in alpha power were maximal at the 2-hour timepoint after 25 mg psilocybin administration, coinciding with maximum subjective intensity.
▪No changes in EEG recorded activity were observed under 1 mg psilocybin administration.

Long-term structural and functional brain changes one month after dosing

▪Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) recordings were done in healthy human volunteers before and one month after 25 mg psilocybin administration.
▪A large sized effect (95% CI [0.33, 1.34], d = 0.9) was found for BOLD fMRI responses to fearful faces versus fixation cross one month post-25mg psilocybin versus one month post-1mg psilocybin (t(24) = −3.85, p = 0.005).
▪No significant differences in axial diffusivity were observed following 1 mg psilocybin administration.
▪Significant decreases in axial diffusivity (AD) were observed one month after 25 mg psilocybin in a prefrontal cortex-thalamus tract (PFC-THA; F(2, 48) = 9.51, p = 0.008).
▪Post-hoc t-tests found significant decreases in axial diffusivity one month post-25mg psilocybin versus one month post-1mg for the prefrontal cortex-striatum tract (t(24) = −3.72, p = 0.006).
▪Significant decreases in axial diffusivity (AD) were observed one month after 25 mg psilocybin in a bilateral prefrontal cortex-striatum tract (PFC-STR; F(2, 48) = 10.30, p = 0.005).
▪Statistically significant group-average decreases in brain network modularity were not observed one month post-25 mg versus one month post-1 mg psilocybin (p = 0.209; d = 0.3).
▪No statistically significant changes in within- or between-network resting-state functional connectivity were observed at one month post-25 mg psilocybin versus one month post-1 mg psilocybin.
▪A statistically significant decrease in brain network modularity was observed one month post-25mg psilocybin when contrasted against pre-dose baseline (t(24) = −2.95, p = 0.007; d = 0.6).