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 via OpenAlex
Summary
AI-generated from the abstractA single dose of psilocybin substantially alters the prefrontal cortex transcriptome in mice 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. Sub-chronic microdosing also has no metabolic effects, does not augment GLP-1-induced weight loss, and does not enhance diet-induced weight loss. A single high dose reduces sucrose preference but fails to counter binge-like eating behavior. These preclinical data discourage clinical investigation, though nuances in psychedelic drug action may require human evaluation.
Study at a glance
| 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 |
| Citations | 47 |
| Key finding | 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.