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.
Alcohol use disorder (AUD) is a major medical problem with limited treatments. (R)-ketamine, a form of the dissociative psychedelic with fewer dissociative and anesthetic effects than the racemic mixture, reduced alcohol consumption in female but not in male Marchigian Sardinian alcohol-preferring (msP) rats when given orally at doses of 10, 20, and 40 mg/kg in a two-bottle free choice 24-hour drinking paradigm. No effect was observed on alcohol self-administration. (R)-ketamine also attenuated the retrieval of alcohol-related memories in female but not in male rats. These results suggest (R)-ketamine attenuates alcohol-related behaviors in a sex-dependent manner, with females showing higher sensitivity, supporting clinical investigation in patients with AUD.