Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats
Ivan Skorodumov, Rainer Spanagel, Jonathan R Reinwald, Christian N. Schmitz, Martin Kuchař, Wolfgang Weber‐fahr, Marcus W. Meinhardt
Translational Psychiatry December 14, 2023 DOI: 10.1038/s41398-023-02690-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, placebo-controlled crossover pharmaco-fMRI study Peer reviewed |
|---|---|
| Population | Healthy rats and a rat model of alcohol relapse |
| Intervention | Psilocybin |
| Topics | Addiction Default mode network Psilocybin |
| Keywords | Hallucinogen Pharmacology |
| Citations | 25 |
| Key points | Psilocybin induced acute widespread decreases in functional connectivity and DMN hypoconnectivity, but alcohol relapse severity was negatively correlated with neural responsivity to psilocybin, suggesting a standard dose may be insufficient for severe AUD. |
Abstract
Abstract Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin’s general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.
Comparable studies
Other preclinical and animal studies on psilocybin for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism | 2021 | Preclinical study | |
| Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse Male and female rats | 2020 | Preclinical animal study | |
| Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories. Male and female Marchigian Sardinian alcohol-preferring (msP) rats | 2023 | Preclinical experimental study | |
| Sex-specific role of the 5-HT2A receptor in psilocybin-induced extinction of opioid reward. Male and female mice | 2025 | Experimental study |
Citations in the library
Cited by 15
- Potential Differences in Psychedelic Actions Based on Biological Sex. Endocrinology July 1, 2024
- Psilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial EClinicalMedicine March 14, 2025
- The Emergence of Psilocybin in Psychiatry and Neuroscience Pharmaceuticals April 9, 2025
- Classic psychedelics and the treatment for alcoholism. Progress in Neuro-Psychopharmacology and Biological Psychiatry December 20, 2024
- Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats Frontiers in Neuroscience May 1, 2025
and 10 more in the library
Cites 42
- 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
- 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
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 37 more in the library