Psilocybin and its metabolite psilocin produce psychedelic effects by activating the 5-HT2A receptor. While proposed as a treatment for depression and anxiety, psilocybin can also induce acute anxiety. In mice, psilocybin increased anxiety in behavioral tests. Blocking the 5-HT2A receptor reduced the head twitch response (a proxy for psychedelic effects) but did not prevent the anxiety-related behavior. Phosphopeptide analysis of the amygdala revealed signal transduction pathways both dependent and independent of the 5-HT2A receptor. Presynaptic proteins were specifically involved in psilocybin-induced acute anxiety. These findings suggest that anxiety and psychedelic effects involve separable mechanisms, informing clinical use.
Psilocybin, a psychedelic compound from hallucinogenic mushrooms, causes changes in visual perception, but the molecular mechanisms in vision-related brain regions were unknown. In mice, psilocybin induced robust gene expression changes in the visual cortex that closely mirror those caused by light exposure, even when mice were kept in the dark. These changes involve synaptic functioning and specific neuron subtypes. Combined psilocybin and light exposure produced synergistic effects on genes related to epigenetic programming. The findings suggest psilocybin alters visual cortex gene expression in ways that may affect visual perception both independently and together with visual experience.