Inserm researchers have highlighted the potential of psilocybin, the active compound in hallucinogenic mushrooms, in alcohol use disorders. Their work also explores the previously unknown mechanisms of action of this molecule. Communicated.
This unprecedented study, carried out by Professor Mickael Naassila and his team from the Research Group on Alcohol and Drug Dependence (GRAP, UPJV/INSERM 1247 laboratory), opens new therapeutic perspectives for the treatment of alcohol addiction. with psilocybin, the active compound in hallucinogenic mushrooms. Published in the scientific journal Brain, vsThis work confirms the potential of psilocybin to combat alcohol addiction, while revealing the previously unknown mechanisms of action of this molecule. A very promising scientific breakthrough for curbing the scourge of alcohol addiction using psychedelics.
Psilocybin reduces alcohol self-administration through selective activation of the left nucleus accumbens
The results of the study conducted by scientists from Inserm and UPJV show that the administration of psilocybin in mouse models of alcohol addiction reduces their alcohol consumption by half. These data confirm the interest in studying this molecule in the treatment of alcohol dependence.
To explain these effects and better understand the underlying mechanisms, researchers measured, in the brain at the level of the nucleus accumbens, the expression of certain genes known to be involved in alcohol addiction. The nucleus accumbens plays a central role in addiction, notably by relaying the pleasant effects of drugs and the motivation to consume them.
The results surprisingly reveal a cerebral lateralization in the effects of psilocybin, with a modification of the expression of certain genes, either upwards or downwards and which is different depending on the left or right side of the brain. brain.
These initial results therefore pushed researchers to explore the specific role of the left or right nucleus accumbens by directly injecting psilocybin either into the left nucleus accumbens or into the right.
Psilocybin injected into non-alcohol consuming rats induced peculiar changes in the brain, including a decrease in the expression of 5HT-2A serotonin receptors only in the left nucleus accumbens. Unexpectedly, the increase in the expression of the BDNF gene, associated with brain plasticity, was observed only in the right nucleus accumbens.
When psilocybin is injected directly into the left nucleus accumbens, it cuts alcohol consumption in half, but it has no effect when injected into the right nucleus accumbens.
A better understanding of the mechanism involved in the beneficial effects of psilocybin on alcohol consumption
The study by Professor Naassila’s team then went even further to decipher the biological mechanism of psilocybin. We know that the hallucinogenic effects of psilocybin are linked to its action on 5-HT2A serotonin receptors. In this work, the researchers showed that these receptors were overexpressed after treatment with psilocybin. Then, to really demonstrate that the effects of psilocybin on alcohol consumption are linked to a specific effect on 5-HT2A serotonin receptors, they tested the effect of blocking these receptors.
And indeed, infusing ketanserin, a 5HT-2A receptor blocker, directly into the left nucleus accumbens prevents psilocybin from reducing alcohol consumption. This blockage in the right nucleus accumbens is not effective.
The study also highlights another well-known potential mechanism in addiction. Administration of psilocybin increases the expression of dopamine D2 receptors in the nucleus accumbens in alcohol-consuming rats. As we already know that in alcohol addiction, we observe a reduction in the expression of D2 receptors in animals and humans, these results could also explain how psilocybin counteracts the mechanisms of addiction. , by restoring the expression of these receptors.
This unprecedented discovery on the lateralization of the effects of psychedelics in the treatment of alcohol addiction opens new avenues of research. Next steps: carry out a more precise mapping of this lateralization and check if this generalizes to other psychedelics (LSD, DMT, etc.).
According to Professor Mickael Naassila: “These results are very original because they demonstrate that psilocybin acts differently on gene expression depending on the cerebral hemisphere. And that in the brain, it is particularly the nucleus accumbens, but the one located in the left hemisphere, which seems involved in the effects of reducing alcohol consumption.
• Press release of May 22, Find out more on the Inserm website
