Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms.
Juliet Meccia, Joëlle Lopez, Rosemary C. Bagot
Psychopharmacology 2023 DOI: 10.1007/s00213-022-06297-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Psilocybin |
| Keywords | Affect Cognition Medial prefrontal cortex Preclinical models Psychedelics Psilocybin magic mushrooms Hallucinogens Mood disorders Antidepressants Neuroscience brain connectivity Neural networks |
| Citations | 14 |
| Key findings | Acute modulation of prefrontal cortex circuits by psilocybin may contribute to long-term structural and functional alterations that mediate antidepressant effects. |
Abstract
Interest in the therapeutic potential of serotonergic psychedelic compounds including psilocybin has surged in recent years. While human clinical research suggests psilocybin holds promise as a rapid and long-lasting antidepressant, little is known about how its acute mechanisms of action mediate enduring alterations in cognition and behavior. Human neuroimaging studies point to both acute and sustained modulation of functional connectivity in key cortically dependent brain networks. Emerging evidence in preclinical models highlights the importance of psilocybin-induced neuroplasticity and alterations in the prefrontal cortex (PFC). Overviewing research in both humans and preclinical models suggests avenues to increase crosstalk between fields. We review how acute modulation of PFC circuits may contribute to long-term structural and functional alterations to mediate antidepressant effects. We highlight the potential for preclinical circuit and behavioral neuroscience approaches to provide basic mechanistic insight into how psilocybin modulates cognitive and affective neural circuits to support further development of psilocybin as a promising new treatment for depression.
Comparable studies
Other narrative reviews on psilocybin for depression, 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 | |
| Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression | 2021 | Review | |
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review | 2020 | Review | |
| From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders | 2021 | Review |
Citations in the library
Cited by 11
- Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes JAMA Psychiatry December 6, 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
- Limbic System Response to Psilocybin and Ketamine Administration in Rats: A Neurochemical and Behavioral Study International Journal of Molecular Sciences December 20, 2023
- Psilocybin increases optimistic engagement over time: computational modelling of behaviour in rats. Translational Psychiatry September 30, 2024
- New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity Cell Death Discovery May 1, 2024
and 6 more in the library
Cites 64
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- 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
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled 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
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
and 59 more in the library