Effects of a single dose of psilocybin on diet-induced weight loss in obese mice
Ryan J. Keenan, Rezaul Haque, Xianbo Jin, Tomris Mustafa, Jihane Homman‐ludiye, Kayla Elysee, Zi Shan Wee, Stephanie E. Simonds, Claire J. Foldi, Michael A. Cowley
March 31, 2025 preprint DOI: 10.21203/rs.3.rs-6225000/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study |
|---|---|
| Population | Diet-induced obese (DIO) mice |
| Intervention | Psilocybin |
| Dose | a single dose |
| Duration | Four-week period |
| Topics | Psilocybin |
| Keywords | Weight loss Animal science Diet-induced obese Food science Pharmacology Endocrinology Obesity Hallucinogen |
| Key points | Psilocybin exacerbated diet-induced weight loss over four weeks in DIO mice switched to low-fat chow, primarily by modulating food intake without affecting energy expenditure. |
Abstract
Abstract Prolonged obesity induces enduring structural changes within neural circuits that contribute to maintaining the body at an elevated/obese body weight. These circuits regulate various mechanisms which can inhibit extreme or persistent weight loss. Therefore, a potential therapeutic strategy to facilitate weight loss is to promote structural plasticity within the brain. Psychedelic compounds, such as psilocybin, promote neural plasticity caused by a rapid and persistent growth of dendritic spines, which can facilitate the remodelling of neural circuits. Preclinical and clinical studies using psychedelic compounds have demonstrated efficacy for various neuropsychiatric disorders, which are often comorbid with obesity, and share underlying neural mechanisms. Here, we evaluate the effects of a single dose of psilocybin on body weight, food intake and energy expenditure in diet-induced obese (DIO) mice switched onto a low-fat chow. Psilocybin exacerbated diet-induced weight loss over a four-week period in DIO mice and increased the susceptibility for mice to exhibit more profound weight loss. Psilocybin appears to exert these effects predominantly through modulating food intake, with no influence on energy expenditure. No differences were observed in body weight or food intake in DIO mice maintained on a high-fat diet, indicating psilocybin does not necessarily directly promote weight loss or reduce food intake. Rather, it may help facilitate weight loss, provided it is administered in combination with other weight loss promoting interventions. Additional experimentation is required to examine the precise mechanisms involved; however, this data supports further investigation into the use of psychedelic compounds as an adjunct therapy for obesity.
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 |