Effects of a single dose of psilocybin on diet-induced weight loss in obese mice.

A single dose of psilocybin worsened diet-induced weight loss over four weeks in obese mice switched to low-fat chow, making them more likely to lose more weight. The effect came mainly from reducing food intake, not from changing energy expenditure. In obese mice kept on a high-fat diet, psilocybin did not affect body weight or food intake, suggesting it does not directly cause weight loss or reduce eating. Instead, it may help enable weight loss when combined with other weight-loss interventions. The findings support further research into psychedelic compounds as an add-on therapy for obesity, though more work is needed to understand the mechanisms.

Study at a glance

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.