Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia.
3 papers in the library · 44 citations · publishing 2023-2025
Psilocybin, the psychoactive compound in magic mushrooms, shows promise for treating neuropsychiatric conditions like depression and anxiety, though its biological mechanisms remain unclear. A systematic review of 34 preclinical rodent studies found psilocybin most effective for depression, with potential to alter functional connectivity in the brain. Preclinical models allow controlled study of cellular mechanisms and minimize placebo effects, offering translatable insights for future therapies. The review highlights heterogeneity across studies and identifies avenues for further research.
Psilocybin, a serotonergic psychedelic, shows therapeutic potential for depression and anxiety disorders. In a study using serotonin transporter knockout mice—a model for anxiety and depression—a single dose of psilocybin (1 mg/kg) failed to produce head-twitch or hyperlocomotor responses in knockout animals, unlike wild-type mice. Psilocybin did not alter anxiety- or depressive-like behaviors in either genotype, though a trend toward reduced immobility in the Porsolt swim test appeared in female wild-type mice. Female knockout mice uniquely showed anhedonia-like behavior. The findings indicate that functional serotonin transporters are necessary for psilocybin's acute behavioral effects, with implications for pharmacogenetics in humans.
A single injection of psilocybin reduced compulsive grooming in male SAPAP3 knockout mice—a model of obsessive-compulsive disorder—for up to one week, without affecting anxiety-like behaviors. The drug also decreased grooming in female knockout and wild-type mice and increased locomotion in wild-type but not knockout animals, indicating serotonergic dysfunction in the knockout mice. The typical head-twitch response confirmed psilocybin's hallucinogenic-like effect at the dose used. These findings suggest acute psilocybin may offer a novel treatment option for compulsive disorders, addressing the need for alternatives to current therapies that leave many patients unresponsive.