Effect of psilocybin on decision-making and motivation in the healthy rat.
Brianna F Roberts, Alexia L Zylko, Courtney E Waters, Jessica D Crowder, William J Gibbons, Abhishek K. Sen, J Andrew Jones, Matthew S. Mcmurray
Behavioural Brain Research February 25, 2023 DOI: 10.1016/j.bbr.2022.114262 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Healthy male and female rats |
| Intervention | Psilocybin |
| Dose | 1 mg/kg |
| Topics | Psilocybin |
| Keywords | Delay discounting Head twitch response Motivation Probability discounting Progressive ratio Psychedelics hallucinogens Entheogens Psychedelic compounds Rodent research Cognitive function decision-making Executive function |
| Citations | 13 |
| Key findings | Psilocybin at 1 mg/kg did not affect decision-making in probability or delay discounting tasks and did not reduce motivation in a progressive ratio task in rats. |
Abstract
Psilocybin and its active metabolite psilocin are hallucinogenic serotonergic agonists with high affinity for several serotonin receptors. In addition to underlying the hallucinogenic effects of these compounds, serotonin receptor activation also has important effects on decision-making and goal-directed behaviors. The impact of psilocybin and psilocin on these cognitive systems, however, remains unclear. This study investigated the effects of psilocybin treatment on decision-making and motivation in healthy male and female rats. We compared probability and delay discounting performance of psilocybin treated (1 mg/kg) to vehicle rats (n = 10/sex/group), and further assessed motivation in each group using a progressive ratio task. We also confirmed drug action by assessing head twitch responses after psilocybin treatment (1 mg/kg). Results from this study demonstrated that exposure to 1 mg/kg psilocybin did not affect decision-making in the probability and delay discounting tasks and did not reduce response rates in the progressive ratio task. However, psilocybin treatment did cause the expected increase in head twitch responses in both male and female rats, demonstrating that the drug was delivered at a pharmacologically relevant dosage. Combined, these results suggest that psilocybin may not impair or improve decision-making and motivation. Considering recent interest in psilocybin as a potential fast-acting therapeutic for a variety of mental health disorders, our findings also suggest the therapeutic effects of this drug may not be mediated by changes to the brain systems underlying reward and decision-making. Finally, these results may have important implications regarding the relative safety of this compound, suggesting that widespread cognitive impairments may not be seen in subjects, even after chronic treatment.
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 11
- Preclinical models for evaluating psychedelics in the treatment of major depressive disorder. British Journal of Pharmacology October 28, 2024
- Less is more? A review of psilocybin microdosing Journal of Psychopharmacology September 16, 2024
- Effects of psilocybin on uncertain punishment learning. Neurobiology of Learning and Memory September 1, 2024
- Psilocybin as a fast-acting and long-lasting antidepressant for adolescence: Proposing NeuroD1 as a biomarker of its long-term plasticity Biomedicine & Pharmacotherapy October 30, 2025
- Cognitive and affective models of psychedelics in rodents. International review of neurobiology 2025
and 6 more in the library
Cites 17
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- 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
- Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry November 8, 2021
- The paradoxical psychological effects of lysergic acid diethylamide (LSD) Psychological Medicine February 5, 2016
and 12 more in the library