Delayed Anxiolytic-Like Effects of Psilocybin in Male Mice Are Supported by Acute Glucocorticoid Release
N. Jones, Zarmeen Zahid, Sean M. Grady, Ziyad W. Sultan, Zhen Zheng, Matthew I. Banks, Cody J. Wenthur
bioRxiv (Cold Spring Harbor Laboratory) August 14, 2020 preprint DOI: 10.1101/2020.08.12.248229 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Male C57BL/6J mice |
| Interventions | Psilocybin chronic oral corticosterone brief isoflurane anesthesia |
| Duration | One week after drug administration |
| Topics | Psilocybin |
| Keywords | Corticosterone Anxiolytic Glucocorticoid Hallucinogen Antidepressant Pharmacology Endocrinology |
| Citations | 9 |
| Key findings | Acute glucocorticoid release is a relevant biological modifier for the post-acute and long-term behavioral effects of psilocybin in mice. |
Abstract
Abstract Despite observed correlations between acute glucocorticoid release, self-reported anxiety, and long-term treatment outcomes for human studies using psilocybin-assisted psychotherapy approaches, the mechanistic relationship between psychedelic-dependent stress and subsequent behavioral responses remains unclear. Using rodents, direct manipulation of stress-associated hormone responses can be achieved with established pharmacologic models for the assessment of antidepressant and anxiolytic therapeutics. Here, chronic oral corticosterone-induced suppression of the hypothalamic-pituitary-adrenal axis is used to assess the relevance of drug-induced glucocorticoid release on the acute, post-acute, and long-term effects of psilocybin in male C57BL/6J mice. In these studies, psilocybin-induced acute anxiogenesis was found to be correlated to post-acute anxiolysis in a dose-dependent manner. Psilocybin also displayed acute increases in plasma corticosterone, but a post-acute anxiolytic effect in the novelty suppressed feeding test. Both effects were lost when psilocybin was administered in animals pre-exposed to chronic oral corticosterone. A similar long-term interaction between chronic corticosterone and psilocybin administration was observed in an open field test occurring one week after drug administration. Psilocybin administration alone led to more time spent in the center of the arena, but animals spent less time in the center with chronic corticosterone exposure. Intriguingly, these interactive effects were absent in animals exposed to brief isoflurane anesthesia after drug treatment. Overall, these experiments identify acute glucocorticoid release as a relevant biological modifier for the post-acute and long-term behavioral effects of psilocybin in mice. Rodent studies are thus suggested as a tractable means to address neuroendocrine mechanisms supporting context-dependent psychedelic effects in mammalian species.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 8
- Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective Frontiers in Psychiatry December 17, 2021
- Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis. International journal of clinical and health psychology : IJCHP 2023
- Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor iScience April 9, 2024
- Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression. Psychopharmacology July 4, 2024
- Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles. Nature Neuroscience June 1, 2025
and 3 more in the library
Cites 32
- 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
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
and 27 more in the library