1080 Psilocybin Elicits Non-Linear Night to Night Changes in Sleep Spectral Power

Abstract Introduction Despite evidence of an acute effect of psilocybin on sleep physiology, its enduring effects beyond the period of acute administration and active metabolism remain unexplored. Within a clinical trial of psilocybin-assisted therapy for alcohol use disorder comorbid with major depressive disorder, we monitored sleep for ten continuous nights (3 pre-dose | 7 post-dose) in participants (N=22) undergoing an open-label psilocybin-dosing session. Methods We obtained two frontal bipolar-derivations (AF7-FPZ & AF8-FPZ) of sleep-EEG to quantify whole-night power spectral density (PSD). Artifactual epochs (30s) were rejected automatically using our validated convolutional neural network (CNN) based sleep-state classifier (‘ezscore-f’) before deriving whole-night PSD (10·log10 μV²/Hz) in canonical bands (SWA: 0.5-2Hz, Delta2: 2-4Hz, Theta: 4-8Hz, Alpha:8-13Hz, Sigma:13-15Hz, beta:18-30Hz) from 30s-windowed multitaper spectral analyses using six orthogonal tapers. Night-to-night (N−2 to N+7) changes in PSD displayed evidence of curvilinear trajectories and were modeled through mixed-effects growth-curve models, using 3rd-degree polynomial spline terms with participant-specific random intercepts. Results Across all models, between-participant variance of random intercepts was small (mean ICC=0.66), indicating consistent baseline spectral levels. SWAPSD, ThetaPSD, and AlphaPSD showed no evidence of systematic change, with all spline terms non-significant (all p>0.15), suggesting stable dynamics across nights. In contrast, Delta2PSD showed low-order curvature, with two natural spline (ns) components reaching significance (ns1: p=0.009; ns2: p=0.042), consistent with an increase in nights following dosing followed by stabilization. SigmaPSD demonstrated a similar pattern, with a significant second-order spline component (p=0.017) and a third-order spline component approaching significance (p=0.067). BetaPSD likewise exhibited a small but detectable nonlinear fluctuation, with a significant second-order spline term (ns2: p=0.024). First-derivative estimates from fitted trajectories suggested that Delta2PSD approached its peak at night-five, and subsequently trended toward baseline, whereas SigmaPSD and BetaPSD approached local maxima on night-three, yet values remained above baseline thereafter. Conclusion While SWA, Theta, & Alpha remained stable across nights, night-to-night variability in delta2, sigma, and beta bands were observed characterized by subtle early increases that did not persist across the full observation window. Support (if any) Johns Hopkins Center for Psychedelic and Consciousness Research, Sleep Research Society (Small Research Award), Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation.