A multi-institutional investigation of psilocybin’s effects on mouse behavior
OpenAlex – April 09, 2025
Source: OpenAlex
Summary
A rigorous multi-lab study on the hallucinogen psilocybin, a compound related to tryptophan, revealed surprising acute effects on mouse behavior. Across five labs using ~200 mice, psilocybin acutely increased anxiety but decreased fear expression. However, 24 hours later, this drug, influencing neurotransmitter receptors, showed no replicable persistent effects on reducing anxiety or depression-like behaviors, including anhedonia, or facilitating fear extinction. This finding in psychology and drug studies suggests psilocybin's long-term efficacy for conditions like social anxiety, impacting clinical and developmental psychology, might be less consistent in mice.
Abstract
ABSTRACT Studies reporting novel therapeutic effects of psychedelic drugs are rapidly emerging. However, the reproducibility and reliability of these findings could remain uncertain for years. Here, we implemented a multi-institutional collaborative approach to define the robust and replicable effects of the psychedelic drug psilocybin on mouse behavior. Five laboratories performed the same experiments to test the acute and persistent effects of psilocybin (2 mg/kg, IP) on various behaviors that psychedelics have been proposed to affect, including anxiety-related approach-avoidance, exploration, sociability, depression-related behaviors, fear extinction, and social reward learning. Through this coordinated approach, we found that psilocybin had several robust and replicable acute effects on mouse behavior, including increased anxiety- and avoidance-related behaviors and decreased fear expression. Surprisingly, however, we found that psilocybin did not have replicable effects 24 hours post psilocybin administration on reducing anxiety- and depression-like behaviors or facilitating fear extinction learning. Additionally, we were unable to observe psilocybin-induced alterations in social preference or social reward learning. Overall, our comprehensive characterization of psilocybin’s acute and persistent behavioral effects using ∼200 total male and female mice per experiment spread across five independent labs demonstrates with unique certainty several acute drug effects and suggests that psilocybin’s persistent effects in mice may be more modest and inconsistent than previously suggested. We believe this unusual multi-laboratory, highly coordinated research effort serves as a model for facilitating the generation of replicable results and consequently will reduce efforts based on unreliable and spurious results.