Neuropharmacology
August 21, 2025
James J Gattuso, Geraldine Kong, Bilgenur Bezcioglu et al.
7 citations
Chronic psilocybin given orally to mice at two doses (0.1 and 1 mg/kg) increased sociability in male wild-type mice but did not improve anxiety, compulsive, or depressive behaviors, nor did it induce psychosis-like effects. Psilocybin affected gut motility in a dose-dependent way. While overall gut microbiome diversity remained unchanged, specific bacterial species—Lactobacillus murinus, Lactobacillus animalis, and Alistipes dispar—decreased in male wild-type mice only. A cluster of these bacteria correlated with movement, head-twitch response, and gut motility, distinguishing psilocybin-treated from control mice, suggesting a feedback loop involving serotonin signaling. Other bacterial clusters were linked to startle response and sociability, indicating psilocybin engages distinct neural pathways. The findings underscore the roles of the microbiome and sex in psychedelic research.
Molecular Psychiatry
April 6, 2025
James J. Gattuso, Carey Wilson, Anthony J. Hannan et al.
2 citations
A study in a mouse model of obsessive-compulsive disorder (OCD)-like behaviors tested a psychedelic mushroom extract (PME) for potential therapeutic benefits. The research used SAPAP3 knockout mice, which exhibit compulsive grooming and other OCD-like behaviors. The findings suggest that PME may reduce these behaviors, indicating possible therapeutic effects. This work underscores the need for well-designed preclinical studies in the growing field of psychedelic research for psychiatric disorders.
Psychedelics.
October 28, 2025
James J Gattuso, Bilgenur Bezcioglu, Carey Wilson et al.
1 citation
Psilocybin, a serotonergic psychedelic, shows growing evidence for reducing obsessive-compulsive symptoms. A systematic review of 13 studies (4 clinical trials, 9 preclinical) found that single doses rapidly reduced symptoms in patients with OCD and body dysmorphic disorder. In wild-type mice, psilocybin briefly decreased marble-burying behavior only on the first day. In SAPAP3 knockout mice, a genetic model of compulsive behavior, a single dose produced robust, lasting reductions in excessive grooming, replicated across labs and doses. Chronic hallucinogenic doses did not improve anxiety or compulsive behavior in these mice, but chronic sub-hallucinogenic doses in rats reduced self-grooming and increased synaptic markers in the paraventricular thalamus. The evidence suggests transient clinical effects and lasting anti-compulsive effects in animal models, warranting larger placebo-controlled trials with neuroimaging.
bioRxiv (Cold Spring Harbor Laboratory)
October 24, 2024
James J Gattuso, Carey Wilson, Anthony J. Hannan et al.
1 citation
preprint
Acute psilocybin administration reduced compulsive grooming behavior in male SAPAP3 knockout mice, a model of obsessive-compulsive disorder, for up to eight days after a single injection. The compound did not affect anxiety-like behaviors. Psilocybin increased locomotion in wild-type mice but not in knockouts, suggesting underlying serotonergic differences. Both genotypes showed the typical head-twitch response, confirming the drug's hallucinogenic effect at the 1 mg/kg dose. The findings indicate psilocybin may have enduring anti-compulsive potential.
European Journal of Neuroscience
December 1, 2025
Nina Kleditzsch, James J Gattuso, Anthony J. Hannan et al.
Psilocybin, the active compound in psychedelic mushrooms, is being studied as a treatment for depression. Its metabolite psilocin binds to serotonin receptors and the serotonin transporter (5-HTT). In mice lacking 5-HTT, psilocybin failed to cause hyperactivity or head twitches, suggesting 5-HTT might be involved. To test this, researchers gave mice the selective 5-HTT inhibitor escitalopram before psilocybin. Escitalopram did not block psilocybin's effects on movement or head twitches. This indicates that acute blockade of 5-HTT does not directly mediate these behaviors, and the earlier findings in knockout mice likely stem from developmental changes or altered serotonin levels rather than acute transporter function.
The International Journal of Neuropsychopharmacology
August 1, 2025
Thibault Renoir, J. Gattuso, Bilgenur Bezcioglu et al.
Acute psilocybin reduced compulsive grooming in male mice for up to one week and in both sexes shortly after dosing, but chronic psilocybin did not improve anxiety-like, depressive-like, or compulsive-like behaviors or social deficits. The findings suggest acute psilocybin may help reduce compulsive behaviors, while repeated low-dose use offers limited benefits. The study used SAPAP3 knockout mice, a model of obsessive-compulsive disorder, and found differences in serotonin receptor signaling between genotypes. Results highlight the need for caution as psychedelic-assisted therapy gains approval, especially regarding microdosing.