Psilocybin-induced changes in electroencephalography link acute and long-term effects.

Abstract

<h4>Background</h4>Psilocybin's therapeutic potential is neurophysiologically characterized by acute alpha power reductions and increased entropy. However, the systematic time-course of these changes from administration through the 24-hour sub-acute phase remains poorly characterized.<h4>Methods</h4>In a double-blind, placebo-controlled, crossover trial (<i>N</i> = 20, 10 females), healthy participants received a medium dose ∼0.26 mg/kg of psilocybin. High-density resting-state electroencephalography and psychological states were assessed at baseline, 1, 3, 6, and 24 hours, with a 28-day follow-up.<h4>Results</h4>Psilocybin acutely decreased alpha/beta power and increased gamma-band signal diversity (1-3 hours; returning to baseline at 6 hours). Increased gamma diversity correlated with acute psychological effects (Brief Psychiatric Rating Scale, <i>r</i> = 0.71), with the largest increases observed in participants with lower baseline complexity. At 24 hours, reduced delta/theta power correlated with Positive Life Changes (Persisting Effects Questionnaire) at 4 weeks (<i>r</i> = -0.47 to -0.57) but was independent of acute psychological intensity.<h4>Conclusion</h4>Our findings corroborate known acute effects while identifying a distinct sub-acute "afterglow" associated with long-term outcomes. The dissociation between acute psychology and 24-hour spectral shifts suggests that therapeutic benefits may be driven by sub-acute reductions in top-down cortical hierarchy. These results highlight the significance of the sub-acute window for psychological transformation and suggest normalized diversity as a viable baseline biomarker of individual responsiveness to psychedelic intervention.

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