Nobody Knows How Tylenol Really Works

By Josh Fischman edited by Jeanna Bryner

You’re unlikely to open a medicine cabinet in the U.S. without seeing a bottle of Tylenol, the brand name of a pain reliever and fever reducer also sold generically as acetaminophen. A health care trade association estimates that 52 million consumers use a product containing acetaminophen every week in the U.S. The drug is in the news today after Robert F. Kennedy, Jr., head of the Department of Health and Human Services, implied that acetaminophen that is taken when a person is pregnant can cause autism in that person’s offspring. His statements run counter to the most conclusive scientific evidence to date.

The drug is safe and effective when used as directed, but there is something surprising about it: no one is certain how acetaminophen works to relieve pain and fever.

There are at least two theories about the mechanism of the drug, which was first synthesized in the late 1800s. One is that the medication works by interfering with cyclooxygenase (COX) enzymes, which ultimately lead to the formation of prostaglandins, substances that can heighten pain sensations and drive inflammation and fever. By interfering with one of those COX enzymes, acetaminophen inhibits these prostaglandins from forming, says Steven Dudley, a clinical toxicologist and pharmacist, who directs the Arizona Poison and Drug Information Center at the University of Arizona. “So it’s probably an indirect effect on prostaglandins,” Dudley says.

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The other idea is that the medication acts on body chemicals called endogenous cannabinoids, says Alex Straiker, a neuropharmacologist at Indiana University’s Gill Institute for Neuroscience. Straiker has researched the mechanism and found that acetaminophen inhibited cannabinoid production in rodents and that this reduced their pain response.

“Pain pathways are very complicated,” Straiker says. “So acetaminophen is likely to have multiple targets.” It could affect both prostaglandins and cannabinoids, or it could act on other substances involved in pain perception, such as the neurotransmitter serotonin. Both he and Dudley say the medication’s excellent performance may have reduced scientific interest in understanding the mechanism in order to improve it. “There could be no big incentive to figure out how it works,” Straiker says.

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