A novel compound known as MCH11 has shown promising results in reducing alcohol consumption and the motivation to drink in mice, as revealed by research conducted at the Miguel Hernández University of Elche (UMH) in Spain. The study indicates significant sex-dependent differences in how the compound works, which could lead to personalized treatments for alcohol use disorder. The findings were published in the journal Biomedicine & Pharmacotherapy and represent four years of collaborative research involving 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 affects millions globally and results in approximately 2.6 million deaths each year. According to Abraham Torregrosa, the first author of the study, traditional therapies for this condition have significant limitations, with up to 70% of patients relapsing within the first year of treatment. To explore more effective pharmacological options, the research team examined the endocannabinoid system, which plays a crucial role in regulating pleasure, motivation, and stress related to alcohol consumption.
The compound MCH11 acts as an inhibitor of monoacylglycerol lipase, an enzyme responsible for breaking down 2-arachidonoylglycerol (2-AG), a molecule linked to feelings of well-being and impulse control. By inhibiting this enzyme, MCH11 increases 2-AG levels in the brain, thereby diminishing the urge to drink and alleviating withdrawal symptoms.
“Our results indicate that MCH11 influences nervous-system mechanisms that help manage the drinking impulse without causing undesirable side effects,” explained Jorge Manzanares, the study leader and a professor at UMH. He emphasized the importance of these findings, noting that impulsivity is closely tied to the development and persistence of alcoholism. The treatment was found to be effective and selective in mice, providing both anxiolytic and antidepressant effects without impairing their motor or cognitive functions.
Notably, the experiments demonstrated marked differences between male and female mice. “In males, the treatment showed effectiveness at lower and medium doses, while females required higher doses to achieve similar results,” Manzanares stated. This distinction highlights the necessity for gender-specific treatment approaches in addressing alcohol use disorder.
The research team also investigated the genetic impact of MCH11, finding that it corrects gene alterations associated with alcohol use disorder in both sexes. Using PCR analysis, they confirmed that while both male and female mice benefited from the treatment, females needed higher doses for similar efficacy.
Moreover, the study explored the combined effects of MCH11 and topiramate, an existing medication used for alcohol addiction. “The combination proved to be the most effective,” noted Manzanares, indicating MCH11’s potential as part of a tailored, gender-specific therapy for alcohol use disorder.
While these findings are encouraging, Manzanares cautioned that they are still preliminary. “There is a long road ahead from demonstrating drug efficacy in animal models to its application in human patients,” he concluded.
The research was conducted by a dedicated team at UMH, including Torregrosa, María García Gutiérrez, Daniela Navarro, Francisco Navarrete, and Manzanares. The implications of this study could be significant in addressing the global challenge of alcohol addiction, opening avenues for more targeted and effective treatments in the future.
