Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors
ACS Chemical Neuroscience August 1, 2024 Samuel C Woodburn, Caleb M Levitt, Allison M Koester et al. 28 citations
Psilocybin robustly enhances fear extinction in male and female mice when given acutely before testing, across all doses tested. It also produces long-term improvements in extinction retention and reduces fear renewal in a novel context, though these effects depend on dose. Females may respond to a narrower dose range than males. Administration before fear learning or immediately after extinction does not alter behavior, showing that concurrent extinction experience is necessary. Blocking the 5-HT2A receptor eliminates psilocybin's effects on extinction, retention, and renewal, while blocking the 5-HT1A receptor only attenuates the effect on fear renewal. These findings highlight dose, context, and serotonin receptors as key factors in psilocybin's facilitation of fear extinction.