Psilocybin and the glutamatergic pathway: implications for the treatment of neuropsychiatric diseases.
Izabela Szpręgiel, Agnieszka Bysiek
Pharmacological reports : PR December 1, 2024 DOI: 10.1007/s43440-024-00660-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Psilocybin Serotonin |
| Keywords | Psychedelic medicine Neurotransmitters brain chemicals Neural signaling Glutamate Depression treatment ant Gaba |
| Citations | 18 |
| Key findings | Psilocybin's antidepressant effects appear to stem from increased glutamate release and subsequent GABAergic activity, along with promotion of neuroplasticity via glutamatergic pathways. |
Abstract
In recent decades, psilocybin has gained attention as a potential drug for several mental disorders. Clinical and preclinical studies have provided evidence that psilocybin can be used as a fast-acting antidepressant. However, the exact mechanisms of action of psilocybin have not been clearly defined. Data show that psilocybin as an agonist of 5-HT2A receptors located in cortical pyramidal cells exerted a significant effect on glutamate (GLU) extracellular levels in both the frontal cortex and hippocampus. Increased GLU release from pyramidal cells in the prefrontal cortex results in increased activity of γ-aminobutyric acid (GABA)ergic interneurons and, consequently, increased release of the GABA neurotransmitter. It seems that this mechanism appears to promote the antidepressant effects of psilocybin. By interacting with the glutamatergic pathway, psilocybin seems to participate also in the process of neuroplasticity. Therefore, the aim of this mini-review is to discuss the available literature data indicating the impact of psilocybin on glutamatergic neurotransmission and its therapeutic effects in the treatment of depression and other diseases of the nervous system.
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 3
- Psilocybin as Transformative Fast‐Acting Antidepressant: Pharmacological Properties and Molecular Mechanisms Fundamental and Clinical Pharmacology July 16, 2025
- Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View. Molecular Neurobiology June 4, 2025
- The Potential Role of Psilocybin in Traumatic Brain Injury Recovery: A Narrative Review Brain Sciences May 26, 2025
Cites 10
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl) November 8, 2017
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology November 1, 2020
- The Therapeutic Potential of Psilocybin Molecules May 15, 2021
- Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin ACS Chemical Neuroscience January 11, 2023
and 5 more in the library