Psilocybin rapidly, but not immediately, reverses reward learning deficits in a durable manner in an inflammatory rat model of depressive symptoms

Abstract The serotonergic psychedelic, psilocybin, shows potential for rapid and sustained antidepressant effects but the underlying mechanisms remain unknown. Using a chronic interferon-alpha–induced rat model of depression, we show acute psilocybin (0.3 mg/kg) reverses impaired reward-induced biases within 24hrs, with effects enduring for at least 7 days. This suggests psilocybin can restore blunted reward processing, an effect which could significantly contribute to its sustained antidepressant effects. Competing Interest Statement ESJR has received collboarative grant and contract research funding from Boehringer Ingelheim, Compass Pathways plc, Eli Lilly, IRLab Therapeutics, MSD, Pfizer and Small Pharma. ESJR has been paid as a consultant or invited speaker by Compass Pathways, Pangea Botanicals and Charles River. GG (current) and CT (former) were employed by Compass Pathways Ltd.