Preadministration of Lorazepam Negates the Long-Term Antidepressant-Like Effects of Psilocybin in Male Wistar Kyoto Rats
Psychedelic Medicine December 16, 2025 Sophie Woodruff, Meghan Hibicke, Charles D. Nichols
Psilocybin produced sustained antidepressant-like effects in male Wistar Kyoto rats for up to 9 weeks, as measured by the forced swim test. However, when lorazepam was administered 30 minutes before psilocybin, those antidepressant-like effects were completely prevented, and the rats performed similarly to controls given only saline. At 12 weeks post-treatment, lorazepam was associated with decreased Gria3 gene expression, and psilocybin with increased Gria4 expression in the prelimbic cortex, but the role of these gene changes in antidepressant effects remains unclear. The findings suggest that benzodiazepines may reduce the therapeutic benefits of psilocybin-assisted therapy.