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

Studies reporting the effects of psychedelic drugs on mouse behavior are rapidly emerging. However, the reproducibility and reliability of these effects remain uncertain. Here we implemented a multi-institutional collaborative approach to assess which effects of psilocybin on mouse behavior are robust and replicable. Five independent laboratories performed the same experiments to test the acute and persistent effects of psilocybin (2 mg kg^-1, intraperitoneally) on various behaviors. Psilocybin acutely increased anxiety- and avoidance-related behaviors and decreased fear expression in a robust and replicable manner. Surprisingly, however, psilocybin did not have replicable effects 24 h after administration in terms of reducing anxiety- and depression-like behaviors or facilitating fear extinction learning. Additionally, we did not observe psilocybin-induced alterations in social preference or social reward learning. Our characterization of psilocybin's behavioral effects, using ~200 male and female mice per experiment across five laboratories, demonstrates several robust acute effects and suggests that some of psilocybin's reported persistent effects in mice may be modest and/or inconsistent.