Sporadic use of classic psychedelics and neuropsychological performance: A cross-sectional analysis

Abstract

Background: Evidence on the neuropsychological consequences of classic psychedelics like psilocybin, LSD, and ayahuasca is conflicting, and little is known about how sporadic use of psychedelics under naturalistic conditions may affect cognitive functioning. Given the growing interest in the therapeutic potential of psychedelics and the rise in non-medical use, further exploration into their neuropsychological effects is needed.

Methods: This cross-sectional, exploratory study employed a comprehensive neuropsychological test battery to assess cognitive domains such as executive function, memory, attention, and visuospatial abilities among individuals with mild to moderate lifetime use of psychedelics. Analyses compared all users to non-users, moderate users to matched controls, and adjusted dose-response analyses were conducted within the users group.

Results: From 2611 screened individuals, N = 136 participants (84 psychedelic users and 52 controls) were included. Participants were aged 18-50 years. Neuropsychological performance was broadly equivalent between users and controls. However, matched-pair analyses showed that psychedelic users had a modest advantage in executive functions, especially superior performance on the Wisconsin Card Sorting Test (WCST) (p < .05). Dose-response analyses further corroborated these findings, indicating a positive association between lifetime psychedelic use and performance on the WCST, specifically total errors (p < .001), perseverative responses (p < .001), perseverative errors (p < .001), non-perseverative errors (p = .008), and conceptual level responses (p = .004).

Conclusions: The study did not detect any negative associations between sporadic lifetime psychedelic use and cognition. Instead, a moderate association with executive functioning was found, indicating increased cognitive flexibility in users. Dose-response analyses further supported this relationship.

Keywords: Cognitive flexibility; LSD; Neuropsychological performance; Psilocybin; Psychedelic.