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.
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.
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.