The effects of psilocybin on cognition and emotional processing in healthy adults and adults with depression: a systematic literature review.

Introduction: Psilocybin, a naturally occurring serotonergic agonist in some mushroom species, has shown promise as a novel, fast-acting pharmacotherapy seeking to overcome the limitations of conventional first-line antidepressants. Studying psilocybin effects on cognition and emotional processing may help to clarify the mechanisms underlying the therapeutic potential of psilocybin and may also support studies with people suffering from depression. Thus, this review aims to provide a comprehensive overview of the current literature regarding the effects of psilocybin on these two key areas in both healthy and depressed populations.

Method: A systematic search was performed on 29 January 2024, in the PubMed, EBSCOhost, Web of Science and SCOPUS databases. After duplicates removal, study selection was conducted considering pre-specified criteria. Data extraction was then performed. The quality assessment of the studies was carried out using the Cochrane Collaboration tools for randomized (RoB 2.0) and non-randomized (ROBINS-I) controlled trials.

Results: Twenty articles were included, with 18 targeting healthy adults and two adults with depression. Results point to impairments within attentional and inhibitory processes, and improvements in the domains of creativity and social cognition in healthy individuals. In the population with depression, only cognitive flexibility and emotional recognition were affected, both being enhanced. The comparison of outcomes from both populations proved limited.

Conclusions: Psilocybin acutely alters several cognitive domains, with a localized rather than global focus, in a dose- and time-dependent manner. However, the significant methodological constraints call for further research, in the context of depression and with standardized protocols, with longitudinal studies also imperative.