Neural mechanisms underlying psilocybin’s therapeutic potential – the need for preclinical in vivo electrophysiology
Rebecca Smausz, Joanna C. Neill, John Gigg
Journal of Psychopharmacology May 30, 2022 DOI: 10.1177/02698811221092508 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Default mode network Psilocybin |
| Keywords | Prefrontal cortex Hallucinogen Cognition Neuroimaging Biological neural network Electrophysiology Neurophysiology Consciousness |
| Citations | 60 |
| Key findings | Psilocybin's effects on the default-mode network, particularly the prefrontal cortex and hippocampus, likely mediate its consciousness-altering properties, but contradictory neuroimaging evidence exists, and in vivo electrophysiology may provide a more holistic understanding. |
Abstract
Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting effects. In this review, we outline the current understanding of the neurophysiology of psilocybin’s psychoactive properties, highlighting the need for additional preclinical studies to determine its effect on neural network dynamics. We first describe how psilocybin’s effect on brain regions associated with the default-mode network (DMN), particularly the prefrontal cortex and hippocampus, likely plays a key role in mediating its consciousness-altering properties. We then outline the specific receptor and cell types involved and discuss contradictory evidence from neuroimaging studies regarding psilocybin’s net effect on activity within these regions. We go on to argue that in vivo electrophysiology is ideally suited to provide a more holistic, neural network analysis approach to understand psilocybin’s mode of action. Thus, we integrate information about the neural bases for oscillatory activity generation with the accumulating evidence about psychedelic drug effects on neural synchrony within DMN-associated areas. This approach will help to generate important questions for future preclinical and clinical studies. Answers to these questions are vital for determining the neural mechanisms mediating psilocybin’s psychotherapeutic potential, which promises to improve outcomes for patients with severe depression and other difficulty to treat conditions.
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 52
- Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action? Frontiers in Psychiatry February 10, 2023
- 5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system. Communications Biology July 26, 2023
- The evolution and ecology of psilocybin in nature. Fungal Genetics and Biology June 1, 2023
- Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options. Journal of Clinical Medicine March 17, 2024
- Psilocybin as a lead candidate molecule in preclinical therapeutic studies of psychiatric disorders: A systematic review Journal of Neurochemistry November 29, 2023
and 47 more in the library
Cites 51
- 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 can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- 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
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
and 46 more in the library