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

Background: 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. Methods: In a double-blind, placebo-controlled, crossover trial ( N = 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. Results: 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, r = 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 ( r = −0.47 to −0.57) but was independent of acute psychological intensity. Conclusion: 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.