A multi-institutional investigation of psilocybin’s effects on mouse behavior

Psilocybin, the active compound in magic mushrooms, had several clear and repeatable immediate effects on mouse behavior, including increased anxiety and avoidance and reduced fear expression. However, its effects one day later were not consistent across five different laboratories, and no reliable changes were seen in depression-like behavior, fear extinction learning, social preference, or social reward learning. Using about 200 mice per experiment across five independent labs, the findings show that psilocybin's lasting behavioral effects in mice are more modest and less reliable than previously claimed. This coordinated multi-lab approach highlights the importance of replication for producing trustworthy results.

Study at a glance

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.