High doses of Psilocybe cubensis mushroom, given orally or by injection, produced antidepressant- and anxiety-reducing effects in mice without signs of neurotoxicity. The mushroom's polar aqueous extract, which contained psilocybin and psilocin, was particularly effective. In behavioral tests, the mushroom and its extracts matched the effects of standard antidepressant and anti-anxiety drugs. The lethal dose was greater than 2000 mg/kg, indicating low acute toxicity. These preclinical results suggest the mushroom may be a safe and effective treatment for anxiety and depression.
A review of chemical studies on Psilocybe mushrooms, covering publications from 1958 to 2025, identified at least 50 different metabolites across 32 species. Most metabolites were alkaloids with indole structures, responsible for psychotropic properties, but amino acids, terpenoids, and saccharides were also reported. The genus comprises about 165 hallucinogenic species, yet information on non-alkaloid metabolites remains scarce.
Microdosing an aqueous extract of Psilocybe cubensis mushrooms produces anxiolytic and antidepressant-like effects in mice comparable to a single macrodose and the antidepressant fluoxetine. Over ten days of repeated microdosing, the extract also altered brain electrical activity (electrocorticography), promoted dendritic maturation in hippocampal neurons, and changed corticosterone levels. These findings suggest that P. cubensis may offer a therapeutic alternative for anxiety and depression, with microdosing providing benefits similar to larger doses.