A novel compound developed at the Miguel Hernández University of Elche (UMH) in Spain, known as MCH11, has demonstrated effectiveness in reducing alcohol consumption and the motivation to drink in mice. The study, which highlights significant differences in response based on sex, suggests potential pathways for more personalized treatments for alcohol use disorder (AUD). The findings were published in the journal Biomedicine & Pharmacotherapy.
The research team, comprising members from UMH, the Institute for Health and Biomedical Research of Alicante (ISABIAL), and the Primary Care Addiction Research Network (RIAPAD), spent four years investigating the role of the endocannabinoid system in alcohol addiction. This system, which connects the nervous system to various bodily functions, plays a critical role in regulating pleasure, motivation, and stress—factors that are heavily involved in AUD.
Alcohol use disorder is a major global health issue, responsible for approximately 2.6 million deaths each year. Current treatment options are often inadequate, with up to 70% of patients relapsing within the first year of their recovery. According to researcher Abraham Torregrosa, the limitations of existing therapies highlight the need for innovative approaches.
The study’s focus on MCH11 revolves around its function as an inhibitor of monoacylglycerol lipase, an enzyme that breaks down the endocannabinoid molecule 2-arachidonoylglycerol (2-AG). By inhibiting this enzyme, MCH11 increases the availability of 2-AG in the brain, which is associated with improved impulse control and reduced withdrawal symptoms.
Study leader Jorge Manzanares noted, “Our results show that MCH11 acts on nervous-system mechanisms that help control the drinking impulse, but without undesirable side effects.” This outcome is particularly significant, as impulsive behaviors are closely linked to the development and persistence of alcoholism.
Sex-Dependent Differences in Efficacy
The research revealed notable sex-dependent differences in the compound’s effectiveness. MCH11 was effective at low to medium doses in male mice, while female mice required higher doses to achieve similar results. This disparity underscores the need for sex-specific adaptations in treatment approaches.
Additionally, the researchers conducted genetic analyses that indicated MCH11 could correct gene alterations associated with alcohol use disorder in both sexes, although females again required higher doses for similar effects.
The team also explored the potential of combining MCH11 with topiramate, an existing medication used in clinical settings for treating alcohol addiction. The combination proved to be the most effective, suggesting that MCH11 may serve as a valuable component in a tailored therapy regimen.
Manzanares emphasized the potential for MCH11 to be part of a personalized and sex-adapted treatment strategy. “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 cautioned.
This research, spearheaded by Torregrosa, along with colleagues María García Gutiérrez, Daniela Navarro, and Francisco Navarrete, represents a significant step forward in the quest for more effective treatments for alcohol use disorder. As the field continues to evolve, findings from studies like this could play a crucial role in shaping future therapeutic strategies.
For further details, the full study can be accessed through Biomedicine & Pharmacotherapy.
