For decades, Benadryl has been a go-to drug for allergies, sneezing fits, or a quick fix for sleepless nights. But new research is drawing attention to its potential risks for long-term brain health. A major study led by Shelley Gray, a pharmacist at the University of Washington’s School of Pharmacy, tracked nearly 3,500 adults ages 65 and older who were part of the Adult Changes in Thought study. Over about seven years, 800 participants developed dementia.
When researchers looked closely, they found that those who regularly used anticholinergic medications such as Benadryl were far more likely to develop dementia. In fact, taking one of these drugs for three years or more was linked with a 54 percent higher risk of dementia compared to people who had used them for three months or less. A 2015 study published in JAMA Internal Medicine confirmed these findings, showing a 63 percent higher risk of Alzheimer’s disease for long-term users.
How Benadryl affects the brain
Benadryl’s active ingredient, diphenhydramine, works by blocking histamine, a chemical that triggers allergy symptoms. But it also blocks another critical chemical called acetylcholine, which plays a major role in learning, attention, and memory. As Dr. Malaz Boustani of Indiana University explained, “Acetylcholine is responsible for attention, concentration and memory.” Blocking it too often, especially in older adults whose natural acetylcholine levels are already declining, can worsen confusion and memory loss.
Doctors also warn that diphenhydramine crosses into the brain more easily than newer antihistamines. That’s why it can cause grogginess, poor attention, and even interfere with deep REM sleep. Dr. David Stukus of Nationwide Children’s Hospital put it bluntly: “The feeling is more like being knocked out after having too much to drink, than deep, restorative sleep.”
The risks go beyond dementia
The dangers of Benadryl aren’t limited to memory decline. Older adults taking it face a higher risk of falls, accidents, and daytime confusion. The European Union has even placed diphenhydramine on its “do not drive” list, and airline pilots are barred from flying for two to three days after using it. Studies have shown it can impair driving ability even more than alcohol.
Physicians like Dr. Pamela Tambini caution that patients often underestimate these risks because the drug is sold over the counter. “People sometimes assume these medications must be harmless because they are sold over the counter, but if you use them too often or for too long, they can mess with your thinking, make you groggy during the day, and possibly lead to long-term problems,” she said.
What experts recommend instead
Most doctors agree that occasional use of Benadryl is fine, especially in situations where no alternatives are available. But long-term or frequent use is strongly discouraged. Safer allergy options include second-generation antihistamines like loratadine (Claritin), cetirizine (Zyrtec), or fexofenadine (Allegra), which do not cross into the brain as easily. For sleep, experts suggest improving bedtime habits, using melatonin supplements, or trying cognitive behavioral therapy for insomnia rather than relying on older antihistamines.
Dr. Boustani even helped develop the Anticholinergic Cognitive Burden Scale, which ranks drugs like Benadryl based on their mental side effects. He advises patients to avoid medications with high scores when possible. “There are so many alternatives to these drugs,” he explained.
Doctors stress the importance of reviewing your medications regularly, especially as you get older. Because the body processes drugs more slowly with age, side effects can linger longer. “These drugs aren’t something to take long-term if you want to keep a clear head into old age,” Harvard Health Publishing staff wrote in their review.
Experts say that people should not panic or rush to throw away their medicine cabinets, but they should consider talking with their doctors about alternatives. As Dr. Stukus reminded, “Just because you’ve always done something a certain way, it doesn’t mean it’s the best option available.”
