Preclinical perspectives on the mechanisms underlying the therapeutic actions of psilocybin in psychiatric disorders
Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson
Neuropharmacology March 13, 2023 DOI: 10.1016/j.neuropharm.2023.109504 via OpenAlex
Summary
AI-generated from the abstractPsychedelic compounds like psilocybin show promise for treating neuropsychiatric disorders, with clinical trials demonstrating rapid (within days) and persistent (3-12 months) improvement in treatment-resistant depression. This review examines preclinical models and experimental approaches used to study the neurobiological actions of psychedelic drugs, summarizing insights into mechanisms underlying therapeutic effects, including receptor binding and second messenger signaling cascades. It also discusses potential biological processes such as improvements in synaptic structure and function and suppression of inflammation that may produce lasting symptom amelioration. Better mechanistic understanding will advance these medicines.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Hallucinogen Psychology Psychiatry Psychotherapist |
| Citations | 30 |
| Key finding | Psychedelic drugs like psilocybin induce rapid and persistent improvement in treatment-resistant depression, with mechanisms involving receptor binding, second messenger signaling, synaptic changes, and anti-inflammatory effects. |
Abstract
Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3-12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental approaches that have been used to study the neurobiological actions of psychedelic drugs. We further summarize the insights these studies have provided into the possible mechanisms underlying the induction of their therapeutic actions, including the receptors to which psychedelics bind and the second messenger signaling cascades that they activate. We also discuss potential biological processes that psychedelics may alter to produce the lasting amelioration of symptoms, including improvements in synaptic structure and function and suppression of inflammation. Improved mechanistic understanding of psychedelic drug actions will aid in the advancement of these promising new medicines. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".