A new compound developed at the Miguel Hernández University of Elche (UMH) in Spain demonstrates significant potential in reducing alcohol consumption and motivation to drink in mice. The research, which highlights notable sex-dependent differences in efficacy, could lead to personalized treatments for alcohol use disorder. The findings were published in the journal Biomedicine & Pharmacotherapy after four years of collaborative research by teams 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 a widespread addiction that affects millions globally and results in approximately 2.6 million deaths annually. Currently available therapies often fall short, with up to 70% of patients relapsing within the first year of treatment. According to UMH researcher Abraham Torregrosa, the limitations of existing treatments prompted the search for more effective pharmacotherapy options.
The research team focused on the endocannabinoid system, a critical network that connects the nervous system to various bodily functions and plays a vital role in regulating pleasure, motivation, and stress — all of which are intricately linked to alcohol addiction. In individuals suffering from alcohol use disorder, this system becomes imbalanced, leading to reduced levels of molecules such as 2-arachidonoylglycerol (2-AG), which is essential for well-being and impulse control.
The experimental compound, MCH11, acts 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, effectively decreasing both the urge to drink and withdrawal symptoms. Professor Jorge Manzanares, the study leader, stated that “our results show that MCH11 acts on nervous-system mechanisms that help control the drinking impulse, but without undesirable side effects,” at least in the doses tested on mice.
Gender Differences in Treatment Response
The research findings revealed significant differences in treatment efficacy based on sex. In male mice, MCH11 was effective at low and medium doses, while female mice required higher doses to achieve similar results. Torregrosa noted that the genetic impact of MCH11 is also observable; certain genes altered by alcohol use disorder showed correction through treatment in both sexes, although the dosage differed.
Additionally, the team explored a combination therapy involving MCH11 and topiramate, a medication already used in clinical settings for alcohol addiction. “We found that the combination of both compounds is the most effective,” said Manzanares, emphasizing MCH11’s potential role in personalized, gender-adapted treatment strategies.
Despite the promising results, Manzanares cautioned that the research is still in its early stages. “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 collaborative work was conducted by researchers including Torregrosa, María García Gutierrez, Daniela Navarro, Francisco Navarrete, and Manzanares, all members of the Translational Neuropsychopharmacology Group at UMH. Their findings could potentially lead to more effective treatments for alcohol use disorder, addressing a critical public health issue.
For further information, refer to the study: Abraham B. Torregrosa et al, “MCH11, a new monoacylglycerol lipase inhibitor, reduces ethanol consumption and motivation to drink in mice, with sex-dependent differences,” published in Biomedicine & Pharmacotherapy in 2025. DOI: 10.1016/j.biopha.2025.118662.
