New Compound MCH11 Reduces Alcohol Intake in Mice, Shows Promise

A groundbreaking study conducted at the Miguel Hernández University of Elche (UMH) in Spain has revealed that a new compound, known as MCH11, significantly reduces alcohol consumption and the motivation to drink in mice. The research team identified notable sex-dependent differences in the compound’s effectiveness. While MCH11 is not yet approved for human use, its findings may lead to personalized treatments for alcohol use disorder, a condition that affects millions globally.

The findings, published in the journal Biomedicine & Pharmacotherapy, result from four years of collaborative research involving scientists from the Institute of Neurosciences, the Institute for Health and Biomedical Research of Alicante (ISABIAL), and the Primary Care Addiction Research Network (RIAPAD). Alcohol use disorder is one of the most common addictions worldwide, contributing to approximately 2.6 million deaths annually.

Abraham Torregrosa, the first author of the study, emphasizes the challenges faced by current therapies, noting that up to 70% of patients relapse within the first year of treatment. In pursuit of a more effective pharmacotherapy, the research team focused on the endocannabinoid system, a complex signaling network that connects the nervous system with other bodily functions, including pleasure and stress regulation.

Research indicates that individuals with alcohol use disorder experience an imbalance in this system, leading to decreased levels of molecules such as 2-arachidonoylglycerol (2-AG), which is crucial for well-being and impulse control. MCH11 functions as an inhibitor of monoacylglycerol lipase, an enzyme that breaks down 2-AG. By blocking this enzyme, MCH11 increases the availability of 2-AG in the brain, thereby diminishing both the desire to drink and withdrawal symptoms.

“Our results demonstrate that MCH11 operates on mechanisms within the nervous system that regulate drinking impulses, without causing undesirable side effects,” said Jorge Manzanares, the study leader and professor at UMH. He noted that these findings are particularly significant, as impulsive behaviors are closely associated with the development and maintenance of alcoholism.

In experiments, treatment with MCH11 proved both effective and selective, exhibiting anxiolytic and antidepressant properties while preserving motor and cognitive functions. The research also uncovered significant differences between male and female subjects. “In males, the response to treatment was effective at low and medium doses, while females required higher doses for similar outcomes,” explained Manzanares.

Genetic analysis revealed additional insights, as researchers found that MCH11 corrected gene alterations associated with alcohol use disorder in both sexes. However, the dosage requirements differed, underscoring the necessity for sex-specific treatment approaches.

The team further explored a combined treatment of MCH11 with topiramate, an existing medication for alcohol addiction. They discovered that the combination yielded the most effective results, highlighting MCH11’s potential within a personalized, sex-adapted therapy framework.

Manzanares cautioned that while the results are promising, they remain preliminary. “There is a long road from demonstrating drug efficacy in animal models to applying it in patients,” he concluded.

The collaborative effort was led by Abraham Torregrosa, alongside researchers María García Gutiérrez, Daniela Navarro, Francisco Navarrete, and Jorge Manzanares, all members of the Translational Neuropsychopharmacology Group at UMH.

For more detailed findings, refer to the publication: Abraham B. Torregrosa et al, “MCH11, a new monoacylglycerol lipase inhibitor, reduces ethanol consumption and motivation to drink in mice, with sex-dependent differences,” in Biomedicine & Pharmacotherapy (2025). DOI: 10.1016/j.biopha.2025.118662.