At the University of Kentucky's Sanders-Brown Center on Aging, researchers are uncovering an unlikely solution to one of addiction medicine's most stubborn problems: a drug originally designed to treat dementia may help ease the brain inflammation that makes alcohol withdrawal so dangerous and relapse so likely.
The discovery centers on MW150, an experimental compound that targets p38α MAPK, a signaling pathway strongly linked to inflammation in the brain. When researchers tested the drug in cell culture models during acute alcohol exposure and withdrawal, they observed significant reductions in inflammatory markers—particularly during the withdrawal phase itself. The findings, published in the journal Alcohol, represent an important early signal that compounds already in development for neurodegenerative diseases could someday be repurposed to address a very different crisis.
Alcohol use disorder remains notoriously difficult to treat. Relapse rates stay stubbornly high, especially during withdrawal, when the brain experiences a surge of neuroinflammation that both drives cravings and causes lasting neurological damage. "Alcohol use disorder is incredibly difficult to treat because relapse rates remain so high, especially during withdrawal," said Caleb Bailey, Ph.D., a researcher in the lab of Linda Van Eldik, director of the Sanders-Brown Center on Aging. "We wanted to explore whether reducing inflammation in the brain could potentially lessen some of those effects."
What makes this work particularly compelling is that MW150 and a related drug, Neflamapimod, are not theoretical compounds languishing in basic science. Both are already moving through clinical trials for dementia and other neurodegenerative conditions. That existing development pipeline could dramatically accelerate their journey toward treating alcohol-related conditions if promising findings continue to accumulate. "Because these compounds are already further along in development for other neurological diseases, it raises the possibility that they could someday be repurposed more efficiently for alcohol-related conditions," Bailey explained.
The research team, led by Van Eldik—a nationally recognized expert in neuroinflammation—has spent years developing small-molecule therapeutics targeting inflammation pathways linked to diseases like Alzheimer's. That expertise in brain inflammation positioned them to recognize a connection many might have missed: the neuroinflammatory mechanisms driving neurodegenerative disease and those driving alcohol withdrawal may respond to the same interventions.
For Kentucky, the stakes of this work feel especially concrete. Alcohol and bourbon are woven into the state's cultural identity, yet the Commonwealth faces a genuine public health burden from alcohol use disorder. Even if these compounds never directly change drinking behavior, their neuroprotective effects—reducing brain inflammation and its cascading damage—could meaningfully improve long-term outcomes for people struggling with addiction.
The project also marks a milestone in the career of McKenna Green, an undergraduate researcher from Cadiz, Kentucky, who served as first author on the publication. A recent graduate with dual degrees in psychology and public health, Green joined Van Eldik's lab in 2023 and has been accepted into the university's Cognitive Neuroscience Experimental Psychology doctoral program. For Green, the experience was transformative: "Being able to contribute to research that could someday help people struggling with alcohol use disorder has been incredibly meaningful."