Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism
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Alcohol-induced mGluR2 deficits are restored by psilocybin, resulting in a rescue of pathological behaviors in alcoholism.
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Several studies established a causal role for reduced prefrontal metabotropic glutamate receptor 2 function in craving and relapse responses in preclinical models of alcohol dependence.
“Several studies established a causal role for reduced prefrontal metabotropic glutamate receptor 2 (mGluR2) function in craving and relapse responses in preclinical models of alcohol dependence [48–52].”
A single administration of psilocybin restored mGluR2 expression and reduced operant alcohol-seeking behaviors in alcohol-dependent rats.
“More recently, a single administration of psilocybin was found to restore mGluR2 expression and reduce operant alcohol-seeking behaviors in alcohol-dependent rats [48].”
Preliminary preclinical evidence suggests that psychedelics' psychoplastogenic properties might directly counteract the hypofrontality observed in chronic alcohol exposure, thereby restoring the function of the reflective prefrontal system and its regulatory action on the reward system.
“Preliminary preclinical evidence suggests that psychedelics’ psychoplastogenic properties [44] might directly counteract the hypofrontality observed in chronic alcohol exposure [48], thereby restoring the function of the reflective prefrontal system and its regulatory action on the reward system.”
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- Authors
- Meinhardt, M. W., Pfarr, S., Fouquet, G., Rohleder, C., Meinhardt, M. L., Barroso-Flores, J., Hoffmann, R., Jeanblanc, J., Paul, E., Wagner, K., Hansson, A. C., Köhr, G., Meier, N., von Bohlen und Halbach, O., Bell, R. L., Endepols, H., Neumaier, B., Schönig, K., Bartsch, D., Naassila, M., Spanagel, R., & Sommer, W. H.
- Affiliations
- Heidelberg University (DE)
- Inserm (FR)
- The University of Sydney (AU)
- Universitätsmedizin Greifswald (DE)
- Institute for Anatomy and Cell Biology, Universitätsmedizin Greifswald, Greifswald, Germany.
- Indiana University Indianapolis (US)
- Forschungszentrum Jülich (DE)
- University of Cologne (DE)
- Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
- Université de Picardie Jules Verne, INSERM UMRS, 1247 Amiens, France.
- Corresponding author
- Meinhardt, Marcus W.
- Pfarr, Simone
- Fouquet, Grégory
- Spanagel, Rainer
- Sommer, Wolfgang H.
- ORCID
- Meinhardt, Marcus W.
- Fouquet, Grégory
- Rohleder, Cathrin
- Barroso-Flores, Janet
- Jeanblanc, Jérôme
- Paul, Elisabeth
- Wagner, Konstantin
- Hansson, Anita C.
- Köhr, Georg
- von Bohlen und Halbach, Oliver
- Bell, Richard L.
- Endepols, Heike
- Neumaier, Bernd
- Schönig, Kai
- Bartsch, Dusan
- Naassila, Mickaël
- Spanagel, Rainer
- Sommer, Wolfgang H.
- Venue
- Science Advances
- Published
- 2021-11-19
- Volume
- 7
- Issue
- 47
- Pages
- eabh2399-eabh2399
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC8598005
- OpenAlex
- W3213463597
- Cited by
- 89
- References
- 84
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 25 · 2023: 22 · 2022: 14 · 2021: 2
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc)
- HAL (submittedVersion)
- Funders
- European Commission (668863, HORIZON2020)
- Deutsche Forschungsgemeinschaft (ME 5279/3–1, TRR 265, 402170461)
- Agence Nationale de la Recherche (ANR-18-NEUR-0007)
- Bundesministerium für Bildung und Forschung (01ZX1909A, FKZ: 01EW1908, 402170461, FKZ: 01ZX1909A, 01EW1908)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- psilocybin, mGluR2, alcoholism, alcohol craving, executive dysfunction, cognitive flexibility, alcohol seeking, relapse, prefrontal cortex, viral gene delivery, personalized treatment, pharmacological interventions
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