Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice
- Author: mycolabadmin
- 8/2/2023
- View Source
Summary
This study examined how psilocybin works to reduce anxiety in mice by investigating the role of stress hormones, particularly corticosterone. Researchers found that psilocybin causes a temporary spike in corticosterone levels that is essential for its anxiety-reducing effects hours after administration. Interestingly, other interventions that increase corticosterone levels also produced similar anxiety-reducing effects, suggesting the stress hormone response itself drives the therapeutic benefit rather than psilocybin’s psychedelic properties alone. These findings suggest that measuring cortisol levels in human patients receiving psilocybin therapy could help explain and optimize therapeutic outcomes.
Background
Psilocybin-assisted psychotherapy shows promise for treating anxiety and depression in humans, with correlations observed between acute cortisol elevation and therapeutic outcomes. However, the mechanistic relationship between psychedelic-induced glucocorticoid release and anxiety-like behaviors remains unclear. Animal models allow for controlled manipulation and measurement of these stress-associated hormonal responses.
Objective
To investigate whether psilocybin-induced plasma glucocorticoid release is necessary for post-acute and long-term anxiolytic effects in mice using behavioral assays and pharmacological manipulation of the HPA axis.
Results
Psilocybin induced acute anxiogenic-like effects at 15 minutes but anxiolytic-like effects at 4 hours post-treatment, corresponding with acute corticosterone elevation followed by return to baseline. Blocking glucocorticoid receptor signaling or suppressing psilocybin-induced corticosterone elevation abolished the anxiolytic effects. Non-psychedelic compounds and stress that elevated corticosterone also produced anxiolytic effects, while chronic corticosterone pretreatment abolished psilocybin’s long-term anxiolytic effects.
Conclusion
Transient psilocybin-induced glucocorticoid release is a critical mechanism driving post-acute anxiolytic effects in mice and is necessary for long-term anxiolytic outcomes. These findings suggest HPA axis activation represents an important translational factor for understanding psychedelic-assisted therapy mechanisms and may have implications for clinical outcomes related to set and setting.
- Published in:ACS Pharmacology & Translational Science,
- Study Type:Experimental Animal Study,
- Source: PMID: 37588757, DOI: 10.1021/acsptsci.3c00123