PSILOCYBIN INCREASES HALLUCINATION-LIKE PERCEPTION VIA OVER-RELIANCE ON PERCEPTUAL PRIORS

Psychedelics induce perceptual changes such as hallucinations through unknown mechanisms. In perceptual inference models, hallucinations are thought to arise from an imbalance between perceptual expectations relative to sensory evidence, but it is unclear whether psychedelic-induced hallucinations reflect over- or under-weighting of perceptual expectations. To address this question, we trained rats on an auditory detection task with an explicit confidence report, in which hallucination-like-percepts (HALIPs) were operationalized as high-confidence false alarms. Rats reported the presence or absence of an upsweep signal embedded in background noise across varying signal-to-noise ratios by making a binary choice. Following each choice, rats invested variable time to obtain a randomly delayed reward, providing a behavioral report of decision confidence. Administration of psilocybin (1 mg/kg, i.p.) significantly increased HALIPs relative to control conditions, while leaving overall task performance and confidence reports largely unchanged. Psilocybin-induced HALIPs were abolished by pre-administration of the 5-HT_2A receptor antagonist ketanserin (1 mg/kg, i.p.), implicating 5-HT_2A receptor activation in this effect. Administration of LSD (200 µg/kg) similarly increased HALIPs, indicating that the effect generalizes across classical psychedelics. Bayesian perceptual modeling revealed that psilocybin selectively increased reliance on perceptual priors relative to current sensory evidence. Together, these results establish a behavioral and computational framework for studying psychedelic-induced perceptual changes, and identify increased weighting of perceptual expectations via 5-HT_2A receptor activation as an algorithmic mechanism underlying hallucination-like perception.