Alcohol Use Disorder (AUD) is a debilitating mental health condition impacting over 23 million Americans. AUD causes severe physical and mental suffering and is responsible for high mortality rates and an average of 22 years lower life expectancy.
The disorder is characterized by recurring relapses into excessive alcohol consumption but the exact brain mechanisms responsible for these frequent relapses are not fully understood.
Scientists believe that the disorder is likely linked to poor executive functions and impulse control. A group of German scientists are actively investigating the molecular mechanism of altered executive functions and increased relapses in alcohol dependence. The research focuses on the role of the metabotropic glutamate receptor 2 (mGluR2) which functions as a receptor to regulate the release of glutamate in the brain.
In a recently published report in the journal Science Advances, the research team demonstrated "a causal link between a reduced mGluR2 function within the brain region of the prefrontal cortex in alcohol-dependent rodents and an impaired executive control as well as craving for alcohol. mGluR2 activation has thus been identified as a potential therapeutic mechanism in alcohol dependence." reported Neuroscience New
Psychedelics have long been credited with reducing addictive behaviors. The German researchers sought out to explore whether psilocybin which acts on the serotonin 2A receptors (5-HT2AR) in the brain and bonds with mGluR2 can help regulate mGluR2 levels and restore executive control functions.
“We were able to show that psilocybin can restore mGluR2 levels which leads to a reduction in relapses to alcohol,” said Marcus Meinhardt, the lead researcher. This research opens up the possibility of developing new therapeutic approaches that focus on psilocybin as a driver of mGluR2.
AUD patients commonly demonstrate executive function impairments that increase cravings and lead to relapse. The researchers were able to induce a marked reduction in cognitive flexibility and excessive alcohol-seeking in rats through a neuron-specific prefrontal mGluR2 knockdown. When the researchers administered psilocybin to the same alcohol-dependent rats, they were able to restore mGluR2 expression and reduce relapse behavior.
These findings advance our understanding of the molecular mechanisms behind AUD and lay a foundation for the potential future treatment of alcoholism through psychedelics or pharmaceutical solutions with similar functions.