This Common Painkiller Does Some Interesting Things To Your Mind

As an over-the-counter pain reliever, it's fairly effective at treating pain. But in 2010, a study came out that showing that this medicine-cabinet staple could be influencing us in other ways, too: Acetaminophen was not only able to blunt physical pain, but social pain and rejection too. “Feeling the Pain of Rejection? Try Taking a Tylenol,” suggested Scientific American. “Can Tylenol heal a broken heart?” asked a New York Times Modern Love column.

Since that 2010 paper, a small body of work has continued to accumulate on acetaminophen’s—and potentially other OTC painkillers’—subtle effects on our psychological and cognitive states. In a review paper from last month, Kyle Ratner, an experimental social psychologist at UC Santa Barbara, collected these scattered findings in one place, including some of his own ongoing research into acetaminophen’s effects. In his review, Ratner shows that the ongoing research in this area has expanded beyond just the dulling of social rejection to findings that acetaminophen can change our responses to reminders of our death, the intensity of our mind wandering, or how much we value our possessions.

I asked Ratner: By what means might Tylenol be influencing us in these ways? It's not totally clear, he says, but it may be due to shared spaces in the brain. There’s some imaging research that suggests that social and physical pain could have overlapping biological mechanisms, he tells me, so the parts of the brain that Tylenol affects to make your headache go away are the same parts that are involved in these other feelings as well; the same brain networks that allow us to feel and respond to physical pain may have been co-opted to also feel social pain.

For example, in the early 2000s, a study using fMRI found that the brain regions involved with physical pain also responded to the feeling of social exclusion. The circumstances were created in the lab by having a person play virtual ball toss with two digital people, until they stop throwing the ball to them. When researchers did this, they found that the dorsal anterior cingulate cortex (dACC), a part of the brain also associated with physical pain, was active when the rejection took place.

This concept is what led to the 2010 paper. C. Nathan DeWall, a social psychologist at the University of Kentucky, and his colleagues gave people either acetaminophen or a placebo to take for three weeks. Each night the subjects reported if they had had any hurt feelings or positive emotions. On the ninth day of the study, the people taking the acetaminophen began to report fewer instances of hurt feelings, and did so until the end of the 21-day experiment. Their positive emotions weren’t affected, leading the researchers to think it was just social pain that was being influenced by the acetaminophen.

In a follow up, the authors doubled the acetaminophen dose for three weeks, and had participants play the virtual ball toss game. When they looked specifically at the dACC, they saw that people taking acetaminophen has less of a brain response in those regions than people taking a placebo.

There is a lot of brain signaling going on when you feel pain, including in the somatosensory regions where you actually feel the physical sensation of pain. The dACC's role is a little different, says Steve Heine, a cultural and social psychologist at the University of British Columbia. Heine studies how people make sense of anomalies. “The dorsal anterior cingulate cortex is the region of the brain that's telling you, 'You need to attend to this,'” he says.

The dACC responds to conflicts in our world, like seeing something that’s not supposed to be there, expecting one thing and getting another, incorrect information, and more. Pain can be thought of in this way: we expect and desire to not be in pain, so if it happens, it’s a discrepancy from our expected state, and it sets off an alarm that something is wrong. Psychological pain of any kind may be another kind of cognitive conflict, so Heine thinks that drugs like Tylenol might be more generally blunting our reactions to any conflict at all.

In 2013, Haine and collaborators gave subjects acetaminophen or a placebo, and then presented them with an extremely jarring conflict: the fact that we all are going to die someday. A social psychology theory called Terror Management says that when faced with their mortality, people become more committed to their thoughts and belief systems. But in Heine’s study, he found that people who had taken acetaminophen didn’t react in this way as strongly, when they were asked to write about their own deaths.

Another manipulation of existential anxiety, he tells me, is to show people visual stimuli that don’t make sense, or don’t meet conventional expectations— one way they do this by having subject watch David Lynch videos. People who had taken the acetaminophen also had a blunted response compared to those who took the placebo.

“Our interpretation is they didn't feel the same degree of existential anxiety,” Heine says. “We found that really quite striking because those effects are very far removed from their target of physical pain.”

Heine then teamed up with Todd Handy, a cognitive neuroscientist at the University of British Columbia, who is an expert in EEG, a way of measuring electrical signaling of the brain. In their next experiment, they wanted to see how people would respond to making mistakes on acetaminophen; if drugs like Tylenol were dulling a response to conflict, this could be another way to show it. Handy says that the dACC is typically where the response to making a mistake can be seen.

“It's basically the brain's basic 'oh, shit' response,” Handy tells me. “So we had this prediction that maybe Tylenol, if things are working the way we think it is, it should sort of attenuate this 'oh, shit' effect.”

What they found, along with first author Dan Randles, was that the acetaminophen didn’t dampen the effect—the brain still noticed it was making a mistake—but the signal associated with how much the brain cared that it made a mistake was lessened.

“It was sort of like, 'Hey! I made a mistake, but who cares?'” Handy tells me. “To me this is all sort of consistent with this idea that our brain is always out there looking for anything surprising, anything that needs attention. Physical pain is just one thing that you're constantly monitoring. Overall, you’re asking: Is there any problem that it needs to address? And Tylenol seems to be blunting that.”

Handy's work is mostly centered on attention, and in the past ten years, he has studied mind wandering: that all too common feeling of when you’re talking to somebody, and then you start thinking about what you’re going to eat for dinner, or your date later tonight. Handy's research asks how your brain is responding to its present surroundings when it has decided to wander somewhere else. He’s found, perhaps not surprisingly, that when the mind wanders, our sensory cortices are less sensitive to the outside world. “Our affective responses to the outside world drop off,” he says. “We're less cognitively invested in stuff. So just across the board, everything tunes out.”

He felt like the effects of Tylenol they were seeing were similar to mind wandering. People cared less about social rejection. They didn’t respond as much to existential anxiety; a similar kind of sensitivity reduction to the outside world.

In a new study that hasn’t yet been published, they investigate how Tylenol would impact mind wandering. They subjected people to a repetitive, somewhat boring task—encouraging their minds to wander—and gave half the participants acetaminophen and the other half placebo. “What we found is that when you're on Tylenol, when you're still paying attention to the outside world, everything looks normal,” he tells me. “But when you start to mind-wander, the brain is even better at shutting stuff out. It gives you a deeper mind-wandering state, if you will.”

In 2016, another group found that people who had taken 1,000 mg of acetaminophen might have less empathy for the pain of others. Subjects read different scenarios about people experiencing physical and social pain and reported how distressed they were while reading them. They also were exposed to a loud noise, and rated how unpleasant it was for them, and for another participant. Finally, they observed a game of the virtual ball toss, where a person they didn’t know was being excluded. All of these tasks revealed the same thing: The people who took acetaminophen were less empathic in response to the pain scenarios they read, they were less sensitive to the painful, loud noise, and they didn’t feel as much for the person being excluded from the ball game.

Ratner’s research focused on social groupings. After hearing that acetaminophen could blunt some emotional responses, he wondered if it could influence the types of biases that we have towards people who are like us, and those who aren’t like us.

In 2014, he divided subjects up into two groups in the lab, which can generate positive in-group and negative out-group feelings. He found that people's in-group positivity effect was lessened when they had taken acetaminophen. But in other studies he’s done, he's had confusing results. Using a task where people give out money to each other, he says he didn’t find that acetaminophen had any effect al all. When they’ve also tried to replicate their earlier findings with larger sample sizes, and added in ibuprofen to see its effects, their results moved in the opposite direction: acetaminophen and ibuprofen increased in-group positivity, rather than lessening it. He says they’re not sure why this happened.

Other studies have had weird findings too: a 2014 study that tried to see if ibuprofen could have a similar influence as acetaminophen found that its effects were different by gender. They had men and women play the virtual ball-catching game, and also write about a time they felt betrayed by someone close to them, and a time they felt physical pain.

The women who had taken ibuprofen reported less social pain than the ones who took the placebo, but it was the opposite for men. People are more likely to use first-person pronouns when they’re feeling emotional pain, and the women who took ibuprofen used less first-person pronouns than the placebo group. But again, the men showed the opposite. The researchers theorized that while the women became less sensitized to social pain, the ibuprofen interrupted something else in the men: their tendency to suppress emotional pain. With that dulled, they showed different, and at times opposing effects, as the women.

“My gut feeling right now is these drugs probably do influence our psychologies in really interesting ways that we might not anticipate,” Ratner says of his work and all the other research he compiled for his review. “But we’re just trying to make sense of it all.”

“I think we should absolutely have a scientific concern to recognize the neurocognitive and neuro-affective consequences of substances that we've heretofore thought of as benign,” Handy says. But still, all the researchers that I spoke to think it’s too premature to enact any widespread policy changes, or to strip drugs like acetaminophen and ibuprofen of their over-the-counter status. And they also don’t want to worry people about the magnitude of acetaminophen psychological effects either.

“I don't want to exaggerate how big these effects are, so the practical implications of this remain unknown,” Heine says. “Like, how much are people going to be living their lives differently when they're on Tylenol? I don't think it's going to have a huge impact on them at any given moment. But there might be some situations or some tasks where you really do need to be focused on potential conflict or anything that might cause harm. And in those situations Tylenol does seem to blunt this.” We need to acknowledge that these effects exist and continue to explore how far they reach, he says.

For healthy adults, the effects may be small, but for other groups, there may be more of an impact. Like children, who so often get acetaminophen for fevers and colds: if Tylenol dampens psychological discomfort, Ratner asks, “What are the long-term consequences of blunting emotional processing during early brain development?”

Handy worries about elderly people, for whom falling is often a risk. “You can imagine, you start mind-wandering at the wrong time, like going down the stairs, or negotiating something tricky in your environment, that can lead to a problem,” he says. “Suddenly, you're not paying attention to where your feet need to go, and then you have a fall. So I think in some compromised populations, this could be more of an issue.”

Ratner says there’s also the intriguing possibility that acetaminophen might be used therapeutically one day for people dealing with minor cases of depression or social anxiety. A study from last October found that giving acetaminophen to people with borderline personality disorder might help alleviate their distrust in others. But given that we’re not sure who it works best on, and given that in some studies it shows the opposite effects, we need to know a lot more about exactly what is going on first.

The idea that popping a Tylenol could help you deal with your break up or settle your nerves before a job interview is appealing—but this could be taken too far by people trying to blunt more powerful emotions like depression. Acetaminophen is safe at the right doses, but can become extremely toxic very quickly, easily leading to overdose and liver failure.

Heine says that sometimes, in a tongue-in-cheek way, he now thinks when he’s having a bad day, Maybe I should have a Tylenol. Handy also says the thought has crossed his mind to take a Tylenol before giving talks that might make him a little bit nervous. I ask Ratner if he has changed his own use of Tylenol, and he says he hasn’t.

“I take acetaminophen or ibuprofen for dealing with common aches and pains when necessary, and none of this research makes me really think twice about doing that,” he says. “But I think when I do take it, I am kind of aware of the possibility that these drugs could influence how I'm processing information and evaluating other people. It’s in the back of my mind.”

UPDATE: A representative from Tylenol provided the following statement, which has been edited for length: “The authors clearly state that 'further research is needed' and the reviewed studies administered OTC analgesics to people who were not taking the medicines for physical pain and, therefore, ‘may not apply to the typical person who takes these medications for pain.’ These studies were conducted off-label as you know. The OTC drug facts label has the information that consumers need to appropriately use over the counter analgesics for their self-management of pain and appropriately directs them to speak to their doctor or pharmacist."

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