Blood-pressure drugs were a promising alcohol treatment. In two large cohorts, they did nothing.

Genetics and animal work pointed to L-type calcium channel blockers as a treatment for alcohol use disorder. Checked against the health records of two large US systems, people who started them did not drink less.

Alcohol use disorder has few effective medications, so a credible new target is worth taking seriously. L-type calcium channel blockers, prescribed for blood pressure, had both genetic and laboratory support behind them. Researchers led by Christopher Rentsch tested whether that support survived contact with patients. They ran two preregistered observational cohort studies on electronic health records, one at the US Department of Veterans Affairs and one at Kaiser Permanente Northern California. New users of brain-penetrant calcium channel blockers, nifedipine or felodipine, were compared with new users of amlodipine, a similar drug that does not cross into the brain, and with patients from the same clinics taking neither. Everyone needed a 180-day washout and at least 60 days of supply, and the groups were matched on propensity scores. The outcome was change in drinks per week, measured with difference-in-differences. In the VA, the difference between the brain-penetrant drug and its non-penetrant comparator was 0.14 drinks per week, with a confidence interval from minus 0.06 to 0.34. Against unexposed patients it was exactly 0.00. Kaiser produced the same answer. Prespecified subgroups by diagnosis, drinking level and sex pointed the same way, though some were small. This is observational, so it cannot rule out an effect a trial might find, and people prescribed one blood-pressure drug rather than another differ in ways matching only partly fixes. But two independent systems, preregistered, agreeing on nothing, is a meaningful result. The authors conclude the evidence does not support repurposing these drugs and that other targets deserve the effort instead.