The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action

Abstract

Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin's antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regarding the potential antidepressant properties, we hypothesized that psilocybin, similar to other classical antidepressants, would reduce rapid eye movement (REM) sleep and prolong REM sleep latency. Moreover, we also hypothesized that psilocybin would promote slow-wave activity (SWA) expression in the first sleep cycle, a marker of sleep-related neuroplasticity. Twenty healthy volunteers (10 women, age 28-53) underwent two drug administration sessions, psilocybin or placebo, in a randomized, double-blinded design. Changes in sleep macrostructure, SWA during the first sleep cycle, whole night EEG spectral power across frequencies in non-rapid eye movement (NREM) and REM sleep, and changes in subjective sleep measures were analyzed. The results revealed prolonged REM sleep latency after psilocybin administration and a trend toward a decrease in overall REM sleep duration. No changes in NREM sleep were observed. Psilocybin did not affect EEG power spectra in NREM or REM sleep when examined across the whole night. However, psilocybin suppressed SWA in the first sleep cycle. No evidence was found for sleep-related neuroplasticity, however, a different dosage, timing, effect on homeostatic regulation of sleep, or other mechanisms related to antidepressant effects may play a role. Overall, this study suggests that potential antidepressant properties of psilocybin might be related to changes in sleep.

Keywords: EEG power spectra; Rapid Eye Movement latency; Rapid Eye Movement sleep; antidepressant; neuroplasticity; psilocybin; sleep; slow-wave (delta-wave) sleep.

FIGURE 1

(A) Topographic plots of differences in t-values (Psilocybin–Placebo) in absolute delta power (left) and average absolute delta power in psilocybin (left top) and placebo (left bottom) condition during the first SWS cycle, significant over averaged parietal, temporal and occipital derivations (corrected). (B) Topographic plots as described in (A) for relative delta power with all differences non-significant. The yellow-red dot denotes areas significant at p < 0.01 (corrected).

FIGURE 2

Topographic plots of differences in t-values (Psilocybin–Placebo) in absolute (top) and relative (bottom) spectral power for each frequency band in the REM (top) and NREM (bottom) sleep across the entire sleep period. The yellow-red dot denotes electrodes significant at p < 0.05 (uncorrected). No differences remained significant in both absolute and relative spectral power after correcting for multiple comparisons (Sidak method, all frequency bands, all 19 derivations).