Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor
Ram Harari, Ipsita Chatterjee, Dmitriy Getselter, Evan Elliott
iScience April 9, 2024 DOI: 10.1016/j.isci.2024.109686 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Psilocybin |
| Topics | Anxiety Psilocybin Serotonin |
| Keywords | Pharmacology Hallucinogen Amygdala Receptor |
| Citations | 20 |
| Key findings | Pharmacological blockade of the 5-HT2A receptor attenuates psilocybin-induced head twitch response but does not rescue psilocybin's effect on anxiety-related behavior in mice. |
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.
Comparable studies
Other preclinical and animal studies on psilocybin for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats | 2018 | Experimental study | n = 40 |
| Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming SAPAP3 knockout mice | 2024 | Randomized controlled trial | n = 50 |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study | |
| Novel Psilocin Prodrugs with Altered Pharmacological Properties as Candidate Therapies for Treatment-Resistant Anxiety Disorders Mice and human cellular fractions | 2023 | Experimental study |