Researchers at the Miguel Hernández University of Elche (UMH) in Spain have developed an experimental compound, MCH11, which demonstrates significant potential in reducing alcohol consumption and the motivation to drink among mice. This study, which reveals notable sex-dependent differences in efficacy, represents a promising step towards more effective treatments for alcohol use disorder.
The findings, published in the journal Biomedicine & Pharmacotherapy, are the culmination of 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 is a serious global health issue, responsible for approximately 2.6 million deaths annually. Current treatment methods have significant shortcomings, with up to 70% of patients relapsing within the first year.
The research team, led by Professor Jorge Manzanares, focused on the endocannabinoid system, a crucial network that regulates pleasure, motivation, and stress—all factors closely linked to alcohol addiction. In individuals with alcohol use disorder, the balance of this system is disrupted, leading to reduced levels of molecules like 2-arachidonoylglycerol (2-AG), which are vital for impulse control and overall well-being.
MCH11 works by inhibiting monoacylglycerol lipase, an enzyme that breaks down 2-AG. By blocking this enzyme, the compound increases the availability of 2-AG in the brain, effectively reducing both the urge to drink and withdrawal symptoms. Professor Manzanares noted that the results indicate MCH11 influences nervous-system mechanisms that regulate drinking impulses without causing adverse side effects, at least in the doses tested with mice.
The study revealed that treatment with MCH11 is both effective and selective, showcasing anxiolytic and antidepressant properties without impairing motor or cognitive functions. Nevertheless, the research highlighted significant differences in response based on sex. Males responded positively to low and medium doses, while females required higher doses to achieve similar outcomes.
The genetic impact of MCH11 was also assessed, revealing that it corrects alterations in genes associated with alcohol use disorder in both sexes, although females again needed higher doses. This adds a layer of complexity to potential treatment strategies, underscoring the need for sex-adapted therapies.
In another promising avenue, the researchers explored the effects of combining MCH11 with topiramate, a medication already in clinical use for alcohol addiction. This combination proved to be the most effective, suggesting a potential pathway for developing personalized treatment options tailored to individual needs.
While the results are encouraging, Professor Manzanares cautioned that the research is still in its early stages. He emphasized, “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.”
The research was conducted by a dedicated team at UMH, including Abraham Torregrosa, María García Gutierrez, Daniela Navarro, and Francisco Navarrete. Their work could pave the way for more effective, personalized approaches to treating alcohol use disorder in the future.
