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Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats
Jonathan R Reinwald1,2,3, Christian N Schmitz2,4, Ivan Skorodumov5
1Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Translational Psychiatry
|December 14, 2023
Summary
Psilocybin shows potential for alcohol use disorder (AUD) treatment, but severe AUD cases may require higher doses. This study found that alcohol relapse intensity correlated with reduced brain response to psilocybin.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Alcohol Use Disorder (AUD) affects millions globally with limited effective treatments.
- Psilocybin shows promise for AUD, but its mechanism of action and brain response in AUD patients are not fully understood.
Purpose of the Study:
- To investigate psilocybin's effects on brain connectivity in healthy rats and a rat model of alcohol relapse.
- To explore AUD-specific alterations in brain responsivity to psilocybin.
Main Methods:
- A randomized, placebo-controlled crossover pharmaco-fMRI study in rats.
- Analysis of resting-state functional connectivity, Default Mode Network (DMN) connectivity, and entropy.
Main Results:
- Psilocybin decreased widespread functional connectivity but increased connectivity between serotonergic and cortical regions.
- Translational evidence for psilocybin-induced DMN hypoconnectivity was observed.
- AUD-specific blunting of DMN hypoconnectivity correlated with alcohol relapse intensity.
Conclusions:
- Psilocybin induces acute neural effects in rodents, with translational validity to humans.
- Neural responsivity to psilocybin was negatively correlated with alcohol relapse severity.
- Standard psilocybin doses may be insufficient for severe AUD cases, informing future clinical trial designs.
