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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Hallucinogen Psychotherapist |
| Citations | 30 |
| Key findings | 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".
Comparable studies
Other narrative reviews on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The pharmacology of psilocybin | 2002 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| Psychedelics, Meditation, and Self-Consciousness | 2018 | Review | |
| The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act | 2018 | Review |
Citations in the library
Cited by 27
- Psychedelics: Threshold of a Therapeutic Revolution Neuropharmacology May 27, 2023
- Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms Molecular Psychiatry April 27, 2024
- Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic JAMA Network Open December 5, 2024
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Deciphering psilocybin: Cytotoxicity, anti-inflammatory effects, and mechanistic insights International Immunopharmacology February 23, 2024
and 22 more in the library
Cites 76
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 71 more in the library