Psilocybin increases optimistic engagement over time: computational modelling of behaviour in rats.
Elizabeth L. Fisher, Ryan Smith, Kyna Conn, Andrew W. Corcoran, Laura K Milton, Jakob Hohwy, Claire J. Foldi
Translational Psychiatry September 30, 2024 DOI: 10.1038/s41398-024-03103-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with computational modeling Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Behavioral science Animal research Mental health Psychedelics |
| Citations | 14 |
| Key findings | Psilocybin increased task engagement and reduced loss aversion in rats, suggesting an optimism bias through altered belief updating. |
Abstract
Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit active inference and reinforcement learning computational models to a novel two-armed bandit reversal learning task capable of capturing engagement behaviour in rats. The model revealed that after receiving psilocybin, rats achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.
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 |
Citations in the library
Cited by 13
- The Emergence of Psilocybin in Psychiatry and Neuroscience Pharmaceuticals April 9, 2025
- Psychedelic medicine: mechanisms, evidence, and translation to practice BMJ February 23, 2026
- Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises Molecular Psychiatry April 26, 2025
- The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field Neuroscience & Biobehavioral Reviews May 9, 2025
- Computational Analysis of Psilocybin Effects on Three-Choice Touchscreen Reversal Learning in Rats: A Pilot Study Psychedelic Medicine February 3, 2026
and 8 more in the library
Cites 21
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up Journal of Psychopharmacology February 1, 2022
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
and 16 more in the library