Cells
March 22, 2023
Kevin Domanegg, Wolfgang H. Sommer, Marcus W. Meinhardt
23 citations
Alcohol use disorders remain a major public health problem, and current medications have limited success. Recent clinical trials suggest that psychedelics, especially psilocybin, combined with psychotherapy can reduce heavy drinking. This review connects two lines of research: how addiction alters metabotropic glutamate receptor 2 (mGlu2) function, and how psychedelics act through serotonin 2A receptors (2AR) to induce gene expression and neuroplasticity. Evidence indicates that mGlu2 and 2AR can regulate each other's signaling, either through crosstalk or by forming a 2AR-mGlu2 heteromer, and that 2AR activation can epigenetically modulate mGlu2 expression. The authors propose that targeting these pathways could restore mGlu2 function in AUD patients and reduce relapse risk.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Marcus W Meinhardt, Ivan Skorodumov, Jérôme Jeanblanc et al.
8 citations
A new approach in psychiatric drug development, the preclinical randomized controlled trial (preRCT), was tested across three European centers using a rat model of alcohol relapse. Ketamine (20 mg/kg) reduced relapse, while R-ketamine worked only in females at the same dose; a higher dose (40 mg/kg) was effective in males. The sex-dependent effects were linked to plasma R-ketamine levels, which were twice as high in females. R-ketamine produced a lasting reduction in alcohol consumption without adverse effects. The findings support moving to a clinical trial that accounts for sex differences.
Translational psychiatry
December 5, 2024
Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al.
6 citations
Alcohol use disorder (AUD) impairs prefrontal control mechanisms, leading to reduced inhibitory control and increased relapse risk. Using a biocompatible neuroprosthesis in a rat model of alcohol addiction, researchers measured neural oscillations and event-related potentials during abstinence. Alcohol-dependent rats showed reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity, along with a dominance in higher beta frequencies indicating hyperarousal prone to relapse. Treatment with psilocybin or LY379268 restored these electrophysiological impairments, with psilocybin particularly counteracting the hyperarousal state. These prefrontal markers may serve as indicators of relapse vulnerability and treatment response, especially for psychedelic drugs.
Research Square
February 22, 2024
Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al.
Current treatments for alcohol use disorder (AUD) are often ineffective due to large variability in individual responses and high relapse rates. A precision medicine approach using biomarkers of prefrontal control mechanisms—which are severely disrupted in AUD, reducing inhibitory control and promoting compulsive behavior and relapse—may improve outcomes. In a rat model of alcohol addiction and relapse, a biocompatible neuroprosthesis measured prefrontal neural function during abstinence. Alcohol-dependent rats showed reduced amplitudes of P1N1 and N1P2 event-related potential components and attenuated event-related oscillatory activity. Treatment with psilocybin (a 5-HT2AR agonist) or LY379268 (an mGluR2 agonist) restored these impairments. Psilocybin also counteracted a dominance in higher beta frequencies indicative of hyperarousal prone to relapse. These findings identify prefrontal markers of relapse and treatment response, particularly for psychedelic drugs.