Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

A single dose of psilocin, the active compound in psychedelic mushrooms, alters sleep architecture in mice. Psilocin delayed the onset of REM sleep and reduced NREM sleep maintenance for about three hours after injection, without causing long-term changes in sleep quantity. The acute brain response featured enhanced oscillations around 4 Hz. When mice were sleep-deprived, psilocin did not change the overall amount of sleep rebound, but it slowed the recovery of slow wave activity in the medial prefrontal cortex. These findings suggest that psilocin affects both global vigilance and local sleep homeostasis, which may relate to its potential antidepressant effects.

Study at a glance

Abstract

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the regulation of neuronal firing and activity homeostasis. It remains unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic in vivo electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 hours after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow wave activity. However, psilocin decreased the recovery rate of sleep slow wave activity following sleep deprivation in the local field potentials of electrodes targeting medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.