A novel compound developed at the Miguel Hernández University of Elche (UMH) in Spain has demonstrated an ability to significantly reduce alcohol consumption and the motivation to drink among mice. The study, published in the journal Biomedicine & Pharmacotherapy, highlights notable differences in efficacy based on sex, indicating potential pathways for personalized treatments for alcohol use disorder.
The compound, known as MCH11, is not yet available for human use, but its development could lead to more effective therapies for a condition that affects millions globally. According to the World Health Organization, alcohol use disorder contributes to approximately 2.6 million deaths each year. Abraham Torregrosa, the first author of the study, noted the limitations of existing therapies, revealing that up to 70% of patients relapse within the first year of treatment.
The research team, which includes experts from the Institute of Neurosciences, the Institute for Health and Biomedical Research of Alicante (ISABIAL), and the Primary Care Addiction Research Network, focused on the endocannabinoid system. This complex signaling network regulates pleasure, motivation, and stress—key factors in alcohol addiction. In individuals with alcohol use disorder, an imbalance in this system occurs, leading to decreased levels of molecules like 2-arachidonoylglycerol (2-AG), which play a crucial role in well-being and impulse control.
MCH11 functions as an inhibitor of monoacylglycerol lipase, an enzyme responsible for breaking down 2-AG. By inhibiting this enzyme, MCH11 increases the availability of 2-AG in the brain, subsequently reducing both the urge to drink and withdrawal symptoms. Jorge Manzanares, the study leader, explained that the compound targets mechanisms within the nervous system that help control drinking impulses without producing significant side effects in mice tested.
The treatment proved effective and selective, showing both anxiolytic and antidepressant effects while not impairing motor or cognitive functions. However, the research revealed important sex-based differences in response to MCH11. While male mice responded positively to low and medium doses, female mice required higher doses to achieve similar results.
The genetic impact of MCH11 alongside behavioral changes was also significant. Torregrosa mentioned that the study utilized polymerase chain reaction (PCR) analysis to confirm that MCH11 corrects genetic alterations associated with alcohol use disorder in both male and female mice, although the latter required higher doses for similar effectiveness.
Additionally, the researchers explored the effects of combining MCH11 with topiramate, a medication already in clinical use for alcohol addiction. The findings indicated that this combination was the most effective treatment approach, suggesting that MCH11 could be integrated into a personalized, sex-adapted therapy regimen.
Despite these promising results, Manzanares cautioned that the findings remain preliminary, emphasizing the lengthy path from demonstrating drug efficacy in animal models to potential application in human patients.
The research team, comprising Abraham Torregrosa, María García Gutiérrez, Daniela Navarro, Francisco Navarrete, and Jorge Manzanares, represents the Translational Neuropsychopharmacology Group at UMH. As the understanding of alcohol use disorder evolves, MCH11’s development could herald a new era in addiction treatment tailored to individual needs.
