Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity.
Yingjie Du, Yunfeng Li, Xiangting Zhao, Yishan Yao, Bin Wang, Liming Zhang, Guyan Wang
Chinese medical journal December 20, 2023 DOI: 10.1097/cm9.0000000000002647 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study in mice Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Psilocybin |
| Dose | 2.5 mg/kg, i.p. |
| Duration | 7 days (fear extinction testing on day 1; retrieval and renewal on days 6 and 7) |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Psychedelics Mental health PTSD Treatment Fear response |
| Citations | 71 |
| Key findings | A single dose of psilocybin facilitated rapid and sustained fear extinction in mice, an effect that may be partially mediated by promotion of hippocampal neuroplasticity. |
Abstract
Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 60
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 2025
- Potential Differences in Psychedelic Actions Based on Biological Sex. Endocrinology July 1, 2024
- Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain. Molecular Psychiatry July 1, 2024
- Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors ACS Chemical Neuroscience August 1, 2024
- Impact of psilocybin on cognitive function: A systematic review Psychiatry and Clinical Neurosciences October 1, 2024
and 55 more in the library
Cites 18
- 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
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up Journal of Psychopharmacology February 1, 2022
and 13 more in the library