The depressed state has been theorised to be characterised by an impairment in sleep homeostasis, for example that the need for sleep increases more slowly during wakefulness and so is chronically low in depressed patients. Sleep disturbance is strongly associated with the development and maintenance of many common psychological disorders, including depression. However, slow-wave amplitude and dynamics across the cortical surface reveal a heterogeneity and dependence on both behaviour and neuronal activity levels during previous wakefulness, with evidence for a bidirectional relationship between local neuronal activity and sleep-wake homeostasis. The brain’s homeostatic sleep debt is reflected during non-rapid eye movement (NREM) sleep in the average levels of slow-wave activity (0.5-4 Hz) in neurophysiological field potentials, such as the electroencephalogram (EEG) or intracortical local field potential (LFP). Alongside the circadian rhythm, the occurrence of sleep is itself regulated by a homeostatic principle prolonged wakefulness is compensated by increased sleep intensity, enabling an approximately constant sleep quantity to be obtained each day. The brain-wide changes in neuronal activity occurring alongside the sleep-wake cycle are strongly implicated in the regulation of plasticity of cortical function for example, cellular maintenance, synaptic scaling, firing rate homeostasis, and systems-level memory consolidation are enabled by the sleep state. Neuronal plasticity is not passive but is shaped by ongoing neuronal activity. While the evidence demonstrates that psychedelics can induce structural and functional synaptic plasticity in vivo, facilitate learning and memory, and exert long-lasting behavioural effects in rodents, the specific underlying neurophysiology remains unclear, especially regarding the relevance to psychiatric disorders in humans. The psychedelic state is widely suggested to promote neuroplasticity, which is theorised to be important for psilocybin’s therapeutic efficacy. However, the challenge remains to dissect which neuronal effects are specific to, and necessarily characteristic of, the psychedelic state. Psychedelics act on 5-HT 2A receptors on layer V pyramidal neurones, inhibitory interneurones, and presynaptic thalamocortical afferents across the cortex, most notably prefrontal cortex, modulating glutamate transmission and disrupting neural dynamics and functional networks on a brain-wide scale. Induction of the psychedelic state depends on the metabolite of psilocybin, psilocin (4-hydroxy-N,N-dimethyltryptamine), which acts as a partial agonist of 5-HT 2A receptors. A growing body of evidence suggests that, under appropriate conditions, psilocybin exposure promotes long-lasting positive effects on psychological well-being, offering a promising new treatment method for affective disorders. Psilocybin is a classical serotonergic psychedelic. 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. However, psilocin decreased the recovery rate of sleep slow-wave activity following sleep deprivation in the local field potentials of electrodes targeting the medial prefrontal and surrounding cortex. 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. No long-term changes in sleep-wake quantity were found. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 h after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz.

Here, chronic electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. However, it remains largely unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the homeostatic regulation of neuronal activity and synaptic plasticity.

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. Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood.

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