Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice
Nicole Fadahunsi, Jens Lund, Alberte Wollesen Breum, Cecilie Vad Mathiesen, Isabella Beck Larsen, Gitte M. Knudsen, Anders B. Klein, Christoffer Clemmensen
Translational Psychiatry August 11, 2022 DOI: 10.1038/s41398-022-02103-9 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice (diet-induced obese and genetic mouse models of obesity) |
| Intervention | Psilocybin |
| Dose | a single dose, a single high dose, sub-chronic microdosing |
| Topics | Psilocybin |
| Keywords | Term time Balance ability Hallucinogen Energy balance Schizophrenia object-oriented programming |
| Citations | 47 |
| Key points | Psilocybin has no acute or long-lasting effects on food intake or body weight in obese mice, despite altering the prefrontal cortex transcriptome. |
Abstract
Abstract Psilocybin and other serotonergic psychedelics have re-emerged as therapeutics for neuropsychiatric disorders, including addiction. Psilocybin induces long-lasting effects on behavior, likely due to its profound ability to alter consciousness and augment neural connectivity and plasticity. Impaired synaptic plasticity in obesity contributes to ‘addictive-like’ behaviors, including heightened motivation for palatable food, and excessive food seeking and consumption. Here, we evaluate the effects of psilocybin on feeding behavior, energy metabolism, and as a weight-lowering agent in mice. We demonstrate that a single dose of psilocybin substantially alters the prefrontal cortex transcriptome but has no acute or long-lasting effects on food intake or body weight in diet-induced obese mice or in genetic mouse models of obesity. Similarly, sub-chronic microdosing of psilocybin has no metabolic effects in obese mice and psilocybin does not augment glucagon-like peptide-1 (GLP-1) induced weight loss or enhance diet-induced weight loss. A single high dose of psilocybin reduces sucrose preference but fails to counter binge-like eating behavior. Although these preclinical data discourage clinical investigation, there may be nuances in the mode of action of psychedelic drugs that are difficult to capture in rodent models, and thus require human evaluation to uncover.
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 40
- Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action. Journal of Neuroscience November 8, 2023
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 2025
- Psychedelic Commercialization: A Wide-Spanning Overview of the Emerging Psychedelic Industry. Psychedelic Medicine September 13, 2023
- UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice. Neuropsychopharmacology November 1, 2023
- Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms Molecular Psychiatry April 27, 2024
and 35 more in the library
Cites 21
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
- Long-term follow-up of psilocybin-facilitated smoking cessation The American Journal of Drug and Alcohol Abuse July 21, 2016
and 16 more in the library