Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity
Chronic administration of psilocybin to cafeteria-diet-induced obese rats produced modest but significant reductions in weight gain, high-calorie food intake and central adiposity at the low and high doses. An intermediate psilocybin dose required premature termination, and the positive control metformin produced larger reductions in weight gain than psilocybin.
Authors
- Barr, A. M.
- Huang, J.
- Pham, M.
Published
Abstract
Background
There are currently relatively few effective pharmacological treatments for obesity, and existing ones may be associated with limiting side-effects. In the search for novel anti-obesity agents, drugs that modify central serotonergic systems have historically proven to be effective in promoting weight loss. Psilocin, which is rapidly metabolized from psilocybin, is an agonist at multiple serotonin receptors. In the present study we assessed the effects of psilocybin and a positive control (metformin) on changes in body weight in a rat model of obesity.
Methods
Five groups of adult male rats were pre-conditioned with a cafeteria diet until obese (>600 g) and then treated with either psilocybin (0.1, 1, or 5 mg/kg, i.p.), metformin (300 mg/kg, p.o.) or vehicle control. Treatments were for 27 consecutive weekdays, and body weights and high calorie food intake were recorded daily. Fasting glucose levels were recorded after 11 days of treatment. At the end of treatment rats completed a glucose tolerance test, and multiple fat pads were dissected out to assess adiposity.
Results
The medium dose psilocybin group had to be terminated from the study prematurely. Both the low and high dose psilocybin groups caused a significant decrease in changes in body weight compared to controls. The metformin group produced a greater decrease in change in body weight than either psilocybin groups or controls. Both high dose psilocybin and metformin decreased consumption of the high calorie diet, and exhibited decreased central adiposity.
Conclusion
Psilocybin demonstrated modest but significant effects on weight gain. Further study is recommended.
Research Summary of 'Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity'
Introduction
Hutson and colleagues frame the study within the longstanding interest in serotonergic agents as anti-obesity treatments. They note that drugs which raise synaptic serotonin or act at specific serotonin receptors (notably 5-HT1B, 5-HT2C and 5-HT6) have historically reduced feeding and body weight, but many such agents were withdrawn because of adverse effects. Psilocybin, metabolised to the active compound psilocin, is an agonist at multiple serotonin receptors and has become of interest because of its safety profile in human research and associations in epidemiological data with lower odds of overweight/obesity and improved cardiometabolic self-reports. The authors therefore identify a gap: whether chronic administration of psilocybin can modulate weight gain in a controlled preclinical model of obesity. The present study aimed to determine whether repeated administration of psilocybin alters weight gain in a validated rodent model of diet-induced obesity. Using a cafeteria diet to induce obesity in Sprague-Dawley rats, the investigators compared three doses of psilocybin (0.1, 1 and 5 mg/kg) against an oral metformin positive control (300 mg/kg) and a vehicle control over 27 weekday treatments. Outcome measures included relative change in body weight, consumption of the high-calorie diet, fasting glucose, glucose tolerance and fat-pad measures of adiposity. The authors justify the approach by noting the translational predictive validity of rodent obesity paradigms for human weight outcomes and include a “microdose” condition to reflect emerging interest in sub-perceptual dosing.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Huang, J., Pham, M., Panenka, W. J., Honer, W. G., & Barr, A. M. (2022). Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.891512
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