In a rat model of obesity, psilocybin—a prodrug for the serotonin receptor agonist psilocin—produced modest but significant reductions in weight gain compared to controls. Rats given a low (0.1 mg/kg) or high (5 mg/kg) dose of psilocybin gained less weight over 27 weekdays; the high dose also decreased consumption of a high-calorie diet and reduced central adiposity. Metformin (300 mg/kg) produced a greater decrease in weight gain than either psilocybin dose. A medium-dose psilocybin group was terminated early. Fasting glucose and glucose tolerance were also assessed. The authors recommend further study of psilocybin as a potential anti-obesity agent.
A systematic review of preclinical studies found that extracts from 19 mushroom species and 7 other fungus species nearly all produced antidepressant-like effects in animal models of depression. The review identified 50 relevant studies, mostly in male rodents, using oral administration in acute or chronic regimens. The most common animal model was unpredictable chronic mild stress, while the tail suspension test and forced swim test were frequently used as antidepressant screens. The review discusses each experiment in detail and evaluates the strengths and weaknesses of the studies, highlighting that the antidepressant potential of mushroom and fungus extracts extends beyond psilocybin-containing species to include both psychedelic and non-psychedelic varieties.