Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor
iScience – April 09, 2024
Source: OpenAlex
Summary
Remarkably, Psilocybin, a potent Hallucinogen explored in Medicine for Anxiety, can induce acute anxiety via distinct brain pathways. Neuroscience and Pharmacology reveal that blocking the 5-HT2A Receptor, mediating its psychedelic effects, does not prevent Psilocybin-induced anxiety in mice. Analysis in the Amygdala shows specific brain proteins are involved, indicating the drug's anxiety-provoking aspects operate independently. This insight from Psychedelics and Drug Studies into Neurotransmitter Receptor Influence on Behavior is crucial for developing safer alkaloid-based treatments, informing Psychology and future chemical synthesis.
Abstract
Psilocybin, and its metabolite psilocin, induces psychedelic effects through activation of the 5-HT2A receptor. Psilocybin has been proposed as a treatment for depression and anxiety but sometimes induces anxiety in humans. An understanding of mechanisms underlying the anxiety response will help to better develop therapeutic prospects of psychedelics. In the current study, psilocybin induced an acute increase in anxiety in behavioral paradigms in mice. Importantly, pharmacological blocking of the 5-HT2A receptor attenuates psilocybin-induced head twitch response, a behavioral proxy for the psychedelic response, but does not rescue psilocybin's effect on anxiety-related behavior. Phosphopeptide analysis in the amygdala uncovered signal transduction pathways that are dependent or independent of the 5-HT2A receptor. Furthermore, presynaptic proteins are specifically involved in psilocybin-induced acute anxiety. These insights into how psilocybin may induce short-term anxiety are important for understanding how psilocybin may best be used in the clinical framework.