New Compound MCH11 Reduces Alcohol Intake in Mice, Shows Promise

A new experimental compound, known as MCH11, has demonstrated significant potential in reducing alcohol consumption and the motivation to drink in mice. Research conducted at the Miguel Hernández University of Elche (UMH) in Spain uncovered notable differences in efficacy based on sex, suggesting a path toward more personalized treatments for alcohol use disorder. The findings, detailed in the journal Biomedicine & Pharmacotherapy, represent four years of collaborative research by teams from UMH, the Institute for Health and Biomedical Research of Alicante (ISABIAL), and the Primary Care Addiction Research Network (RIAPAD).

Alcohol use disorder remains a critical global issue, contributing to approximately 2.6 million deaths annually. According to UMH researcher Abraham Torregrosa, who is the first author of the study, existing treatments often fall short, with up to 70% of patients relapsing within the first year of therapy. This stark reality drove researchers to explore the endocannabinoid system, a complex signaling network that plays a vital role in regulating pleasure, motivation, and stress—all crucial factors in alcohol addiction.

The compound MCH11 functions by inhibiting monoacylglycerol lipase, an enzyme that degrades 2-arachidonoylglycerol (2-AG), a molecule associated with well-being and impulse control. By blocking this enzyme, MCH11 increases the availability of 2-AG in the brain, which helps diminish the desire to drink and alleviates withdrawal symptoms.

Jorge Manzanares, the study leader and a professor at UMH, noted, “Our results show that MCH11 acts on nervous-system mechanisms that help control the drinking impulse, but without undesirable side effects,” based on results observed in mice at the tested doses. This is particularly relevant given that impulsive behaviors are closely tied to the onset and persistence of alcoholism.

The researchers observed that MCH11 not only effectively reduced alcohol consumption in mice but also exhibited anxiolytic and antidepressant properties without affecting motor or cognitive functions. However, the study revealed significant sex-dependent differences in treatment response. Males responded effectively to low and medium doses, while females required higher doses for similar effects.

Genetic analysis using PCR techniques indicated that MCH11 helps correct alterations in genes associated with alcohol use disorder in both sexes, although females needed higher dosages for comparable outcomes. The team also assessed the combined use of MCH11 with topiramate, an existing clinical treatment for alcohol addiction, and found this combination to be the most effective approach.

Manzanares emphasized the potential of MCH11 as part of tailored, sex-specific therapies for alcohol use disorder. “The results are very promising, but still preliminary; there is a long road from demonstrating drug efficacy in animal models to applying it in patients,” he concluded.

The research team included Abraham Torregrosa, María García Gutiérrez, Daniela Navarro, Francisco Navarrete, and Jorge Manzanares, all members of the Translational Neuropsychopharmacology Group at UMH. Further details can be found in the study published in Biomedicine & Pharmacotherapy.