Psychedelic Targeting of Metabotropic Glutamate Receptor 2 and Its Implications for the Treatment of Alcoholism
Kevin Domanegg, Wolfgang H. Sommer, Marcus W. Meinhardt
Cells March 22, 2023 DOI: 10.3390/cells12060963 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction |
| Keywords | Metabotropic glutamate receptor Metabotropic receptor Pharmacology Bioinformatics |
| Citations | 23 |
| Key findings | Psychedelics acting through serotonin 2A receptors may restore metabotropic glutamate receptor 2 function in alcohol use disorder, potentially reducing relapse. |
Abstract
Alcohol abuse is a leading risk factor for the public health burden worldwide. Approved pharmacotherapies have demonstrated limited effectiveness over the last few decades in treating alcohol use disorders (AUD). New therapeutic approaches are therefore urgently needed. Historical and recent clinical trials using psychedelics in conjunction with psychotherapy demonstrated encouraging results in reducing heavy drinking in AUD patients, with psilocybin being the most promising candidate. While psychedelics are known to induce changes in gene expression and neuroplasticity, we still lack crucial information about how this specifically counteracts the alterations that occur in neuronal circuits throughout the course of addiction. This review synthesizes well-established knowledge from addiction research about pathophysiological mechanisms related to the metabotropic glutamate receptor 2 (mGlu2), with findings and theories on how mGlu2 connects to the major signaling pathways induced by psychedelics via serotonin 2A receptors (2AR). We provide literature evidence that mGlu2 and 2AR are able to regulate each other’s downstream signaling pathways, either through monovalent crosstalk or through the formation of a 2AR-mGlu2 heteromer, and highlight epigenetic mechanisms by which 2ARs can modulate mGlu2 expression. Lastly, we discuss how these pathways might be targeted therapeutically to restore mGlu2 function in AUD patients, thereby reducing the propensity to relapse.
Comparable studies
Other narrative reviews on addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Mindfulness meditation–based pain relief: a mechanistic account | 2016 | Review | |
| Psychedelics as anti-inflammatory agents Animal models and cellular studies | 2018 | Review | |
| A narrative review of yoga and mindfulness as complementary therapies for addiction. | 2013 | Review | |
| The neuropsychopharmacology of cannabis: A review of human imaging studies | 2018 | Review |
Citations in the library
Cited by 16
- The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews May 1, 2025
- Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Translational Psychiatry December 14, 2023
- Psilocybin and the glutamatergic pathway: implications for the treatment of neuropsychiatric diseases. Pharmacological Reports December 1, 2024
- Unlocking the healing power of psilocybin: an overview of the role of psilocybin therapy in major depressive disorder, obsessive-compulsive disorder and substance use disorder Frontiers in Psychiatry June 11, 2024
- Evaluating the potential for psilocybin as a treatment for post-traumatic stress disorder. Journal of Pharmacology and Experimental Therapeutics 2025
and 11 more in the library
Cites 41
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- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Global Street Food: la cocina de la calle Diseño interior 2009
- Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials Journal of Psychopharmacology March 8, 2012
and 36 more in the library