Impact of psilocybin on cognitive function: A systematic review

Abstract

Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in a range of psychiatric disorders. Evaluating the impact of psilocybin on cognitive function is essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect on cognitive function through a comprehensive search of electronic databases from inception to January 2024, identifying 20 articles involving 2,959 participants. While 85% of studies were conducted in healthy volunteers, most of these studies (85%) used macrodoses, ranging from 45 μg/kg to 30 mg/70 kg. Various cognitive aspects were evaluated and yielded mixed results. Global cognitive function, and processing speed remained mostly unchanged in healthy individuals; However, a limited number of studies reported improvements in certain areas such as sustained attention, working memory, and executive function especially in patients with treatment-resistant depression (TRD). Emotional processing was positively modified, particularly in TRD patients. Psilocybin was observed to enhance emotional empathy without significantly altering cognitive empathy and social cognition. Cognitive flexibility and creative cognition were noted to initially decline but could potentially improve over time. Additionally, with respect to learning and memory skills, psilocybin showed promise in improving specific memory types such as semantic associations and associative learning, while its effects on episodic and verbal memory have been less pronounced compared to other cognitive enhancers. The observed mixed findings underscore the complexity of psilocybin's cognitive influence. Further research is essential to provide a clearer understanding of psilocybin's impact on cognitive domains and to guide the development of safe and effective interventions.

Keywords: cognition; cognitive function; psilocybin; psychedelics; systematic review.

Fig. 1

The Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) flow diagram illustrates the systematic review process, indicating the number of studies included (shown in green) and excluded (shown in red) at each stage.

Fig. 2

Publication year of the published studies until January 2024. Registration year of the included clinical trials, along with their corresponding completion status and reported reasons for trial withdrawal.

Fig. 3

Psilocybin effect on different domains of cognitive function at assessed timepoints during: (a) Post‐acute. (b) Acute phases.

Fig. 4

Psilocybin dose across included studies including macro and microdoses.

Fig. 5

Summary of psilocybin effect on different domains of cognitive function. AUT, alternative uses task; AX‐CPT, AX continuous performance test; CFS, cognitive flexibility scale; COVAT, covert orienting of visual attention task; DSST, digit symbol substitution test; ERT, emotion recognition task; FAIR, Frankfurt Attention Inventory; GMLT, Groton Maze Learning Task; PCET, Penn conditional exclusion test; RAVLT, Rey Auditory Verbal Learning Test; TECA, cognitive‐affective empathy test.