Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor
iScience April 9, 2024 Ram Harari, Ipsita Chatterjee, Dmitriy Getselter et al. 20 citations
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.