Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Viale G. Marconi 446, 00146, Rome, Italy. viviana.trezza@uniroma3.it.
2 papers in the library · 22 citations · publishing 2023-2026
Fragile X syndrome (FXS) is the most common inherited intellectual disability and the leading monogenic cause of autism spectrum disorder (ASD). Serotonin, involved in brain development and synaptic remodeling, may be insufficient during childhood in these disorders, worsening behavioral and emotional symptoms. This study tested psilocybin, a serotonin-modulating compound, in adolescent Fmr1-Δexon 8 rats—a model of both ASD and FXS. Systemic and oral microdoses of psilocybin normalized the rats' performance on the novel object recognition test, a measure of exploratory behavior, perception, and recognition. The results suggest that psilocybin may help ameliorate cognitive deficits associated with ASD and FXS.
In a rat model of Fragile X Syndrome (FXS), psilocybin microdosing rescued deficits in novel object recognition memory. This benefit persisted even when serotonin receptors (5HT2AR or 5HT1AR) were blocked, but was abolished by blocking the TrkB receptor, indicating that the effect depends on BDNF/TrkB signaling rather than classical serotonergic pathways. At the molecular level, psilocybin normalized mature BDNF, increased TrkB, and restored downstream AKT signaling in the prefrontal cortex—pathways linked to synaptic plasticity and cognition. These results suggest psilocybin microdosing could be a promising therapeutic strategy for neurodevelopmental disorders like FXS and autism spectrum disorder, potentially dissociating therapeutic benefits from hallucinogenic effects.