Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice

This mice study finds brain changes (prefrontal cortex transcriptome) but no acute nor long-lasting effects on food intake or bodyweight in obese mice after psilocybin administration. Though it’s difficult to translate to humans, the study suggests no non-psychological route through which psychedelics (psilocybin) can help with eating disorders.

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.”

Authors: Nicole Fadahunsi, Jens Lund, Alberte W. Breum, Cecilie V. Mathiesen, Isabella B. Larsen, Gitte M. Knudsen, Anders B. Klein & Christoffer Clemmensen

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Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice

https://doi.org/10.1038/s41398-022-02103-9

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Published in
Translational Psychiatry
August 11, 2022
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Study details

Topics studied
Eating Disorders

Study characteristics
Animal Study

Authors

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Gitte Knudsen
Gitte Moos Knudsen is the Chair Professor at the Neurology and Neurobiology Research Unit, Copenhagen University Hospital, and director of the Center for Experimental Medicine Neuropharmacology (NeuroPharm).

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