Experts estimate that roughly one in three Americans lives with some degree of liver disease—more than 100 million people in total. Many of them may be unknowingly putting further strain on their liver through everyday medications they assume are safe.

The concern grew serious enough that in 2011, the U.S. Food and Drug Administration (FDA) took action. Regulators urged drug manufacturers to cap the amount of acetaminophen in combination medications—such as Tylenol PM—at 325 milligrams per tablet.

The reason was clear: research showed that higher doses offered little added pain relief, yet significantly increased the risk of liver damage.

Despite this, Tylenol PM still delivers 500 milligrams of acetaminophen per pill.

Diphenhydramine: Sleep Now, Side Effects Later

The second active ingredient in Tylenol PM is diphenhydramine, better known as Benadryl. This antihistamine is what causes the sedating effect that helps people fall asleep. However, that drowsiness comes with trade-offs—especially when the drug is used regularly rather than occasionally.

While it may make sleep come easier in the short term, repeated use can carry cognitive and neurological consequences that many users never anticipate.

Diphenhydramine belongs to a class of drugs known as anticholinergics, meaning it interferes with the brain chemical acetylcholine. This chemical plays a critical role in memory, learning, and overall cognitive performance.

When acetylcholine is blocked too frequently or over long periods, problems can emerge. Research has found that individuals who used anticholinergic medications daily for three years or more faced a 54% greater risk of developing dementia compared with those who used them only occasionally.

Diphenhydramine can also cause a range of side effects, including:

Dry mouth

Lightheadedness or dizziness

Confusion, particularly in older adults

Urinary retention, which can lead to additional complications in the elderly

Dr. Melillo points out that while these effects may seem mild on their own, they can set off or worsen age-related issues—raising the risk of falls, dehydration, and episodes of delirium.

Tylenol PM and Riskier Choices?

Here’s an unexpected twist: acetaminophen may influence how you feel—and how you judge risk.

In a 2020 study from Ohio State University, participants were given either 1,000 milligrams of acetaminophen or a placebo. They were then asked to evaluate how risky various activities seemed, from skydiving and bungee jumping to major life decisions like changing careers.

The results were surprising. Those who took acetaminophen consistently rated these activities as less risky than participants who hadn’t taken the drug. Researchers suggest the medication may dull emotional reactions, softening feelings such as fear and excitement alike.

Earlier research supports this idea, showing that acetaminophen can also reduce empathy, dampening emotional responses to others’ pain—and even muting positive feelings like happiness.

In other words, this widely used medication may do more than ease pain or help with sleep. It could subtly alter how you experience emotions and interpret the world around you.

So What Should You Do Instead?

Dr. Melillo isn’t calling for Tylenol PM to be taken off the shelves. He agrees it can be useful on occasion. But he’s firm about one thing: it shouldn’t become a nightly habit.

For ongoing sleep problems, he recommends speaking with a doctor or pharmacist about options such as:

Sleep aids that don’t create dependence

Melatonin or other natural supplements

Improving sleep habits—cutting back on screens, avoiding caffeine after midday, and sticking to a regular bedtime

Cognitive behavioral therapy for insomnia (CBT-I), which research shows works better than medication over time

If nighttime pain is the real issue, consider approaches like:

Using acetaminophen only when necessary, not routinely Continue reading…