Psilocybin asymmetrically modulates outcome-based choice and cortical processing under uncertainty.
David S Jacobs, Alejandro Torrado Pacheco, Randall J. Olson, Angela J Langdon, Bita Moghaddam
bioRxiv : the preprint server for biology August 13, 2026 preprint DOI: 10.64898/2026.07.16.733837 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Rodents |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Key findings | Psilocybin improved choice selection in uncertain contexts and shifted reinforcement learning rates bidirectionally, enhancing updating from rewarded while reducing updating from unrewarded actions, with corresponding changes in neural encoding of task features. |
Abstract
Emerging clinical research with psilocybin highlights the value of the psychedelic experience on successful treatment of a multitude of psychiatric disorders. While the psychedelic trip or clinical support procedures cannot be modeled in rodents, neural processes critical to meta-learning and flexible modification of previously learned strategies can be quantified during psilocybin exposure. Here we applied computational modeling and single unit recordings from medial prefrontal cortex to characterize the effect of psilocybin using a value-based probabilistic choice task. Psilocybin improved choice selection in uncertain contexts and shifted reinforcement learning rate bidirectionally, enhancing updating from rewarded, while reducing updating from unrewarded, actions. These behavioral changes coincided with selective shifts in the neural encoding of task features including enhanced neural representation of rewarded, and diminished representation of unrewarded, outcomes. Collectively these data indicate that psilocybin improves choice selection in uncertain contexts by reweighing cortical coding in a way that favors learning from positive new information over prospective actions.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |