Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice.
Nicole FadahunsiJens LundAlberte Wollesen BreumCecilie Vad MathiesenIsabella Beck LarsenGitte Moos KnudsenAnders Bue KleinChristoffer ClemmensenPublished in: Translational psychiatry (2022)
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.
Keyphrases
- weight loss
- bariatric surgery
- high fat diet induced
- roux en y gastric bypass
- body weight
- weight gain
- drug induced
- high dose
- gastric bypass
- insulin resistance
- liver failure
- prefrontal cortex
- metabolic syndrome
- glycemic control
- physical activity
- type diabetes
- stem cells
- gene expression
- endothelial cells
- body mass index
- small molecule
- genome wide
- respiratory failure
- mouse model
- electronic health record
- intellectual disability
- intensive care unit
- risk assessment
- white matter
- high glucose
- cell therapy
- dna methylation
- functional connectivity
- artificial intelligence
- multiple sclerosis
- induced pluripotent stem cells
- oxidative stress