Pharmacological Research
December 29, 2025
Martina Colognesi, Daniela Gabbia, Anna Signor et al.
3 citations
Chronic low-dose psilocybin (0.05 mg/kg) reduced body-weight gain, liver steatosis, hyperglycemia, and insulin resistance in mice fed a high-fat/high-fructose diet, without causing central nervous system effects. Multi-omics analyses showed near-complete normalization of disrupted hepatic lipid and carbohydrate metabolism pathways. Psilocybin also improved muscle strength and function, potentially through restoration of leptin sensitivity. The metabolic benefits were independent of the psychedelic target 5-HT2A and instead resulted from antagonism of the serotonin 5-HT2B receptor in the liver, supporting psilocybin as a potential novel therapeutic for metabolic disorders.
Journal of Medicinal Chemistry
January 26, 2026
Marco Banzato, Martina Colognesi, Lorena Lucatello et al.
A library of fluorinated reversible N-alkyl carbamate derivatives of psilocin was designed and synthesized to reduce acute psilocin exposure and limit hallucinogenic-like effects. By varying the number and positioning of fluorine atoms on the alkyl promoiety, carbamate bond stability was systematically modulated, yielding compounds with finely tuned hydrolysis under physiological conditions. A lead compound (4e) demonstrated favorable oral bioavailability and efficient brain penetration while undergoing partial bioconversion to psilocin. It exhibited intrinsic serotonergic activity at 5-HT2A and 5-HT2C receptors but induced attenuated psychotropic effects compared to psilocybin. Fluorinated carbamate chemistry provides a versatile platform to control psilocin exposure and serotonergic signaling.
The International Journal of Neuropsychopharmacology
February 1, 2025
Sofia Nasini, Sara Tidei, Benedetta Barzon et al.
Repeated low-dose psilocybin (0.05 mg/kg) given to adult male mice for 30 days was safe and well tolerated, with no effect on body weight. The treatment produced anxiolytic-like effects: mice spent more time in the light compartment of the light/dark box, showed shorter latency to choose the first arm in the T-maze, and reduced grooming in the open field. No changes were seen in the elevated plus maze, forced swim test, or sociability test. In the cued Morris water maze, psilocybin-treated mice reached the submerged platform faster across all three days and made more successful trials on days 1 and 2, suggesting possible enhancement of spatial memory and learning that requires further study.