Psilocybin intoxication did not affect daytime or sleep-related declarative memory consolidation in a small sample exploratory analysis

Introduction

Psilocybin is a classical serotonergic psychedelic being investigated as a fast-acting antidepressant and adjunct to psychotherapy. Earlier research shows that psilocybin acutely alters sensory perception and cognitive processing, and in preclinical models it can increase synaptic plasticity and dendritic spine growth in medial prefrontal cortex. At the same time, sleep—particularly the first post-learning night and slow wave activity (SWA)—is important for declarative memory consolidation, and prior human work by the authors showed psilocybin increased REM latency but decreased SWA in the first sleep cycle. Taken together, these lines of evidence leave open whether psilocybin affects consolidation of memories learned shortly before or after an acute psychedelic session, and whether post-psilocybin sleep-related consolidation is altered. Nikoli and colleagues set out to test whether a single, weight-adjusted oral dose of psilocybin influences declarative memory consolidation in two arrangements: (A) learning of spatial and verbal material immediately before dosing with delayed recall after the acute effects subsided, and (B) learning of paired associates in the evening after dosing with recall tested before and after the first post-dose night to probe sleep-dependent consolidation. Based on preclinical signals of heightened plasticity, the investigators hypothesised that psilocybin would improve consolidation of newly formed memories and that post-psilocybin first-night sleep would augment this effect.