An unexpected side effect of a popular OTC medication

By Naveed Saleh, MD, MS
Published April 2, 2021

Key Takeaways

No medication is more banal than acetaminophen. This drug is used in more than 600 medications and is one of the most popular OTC drugs in the United States. But for an everyday medication, its effects on cognition are surprising, therefore making it much more than just an analgesic and antipyretic. Current studies and earlier research have demonstrated that it blunts emotions and decreases hurt feelings, also known as social pain.

According to the authors of an experimental study published in Social Cognitive and Affective Neuroscience, acetaminophen can also increase risk-taking behaviors. This effect of acetaminophen could interfere with important decisions involving health care.

“Acetaminophen seems to make people feel less negative emotion when they consider risky activities—they just don’t feel as scared,” said Baldwin Way, PhD, co-author of the study and associate professor of psychology at The Ohio State University, in an article in Neuroscience News. “With nearly 25 percent of the population in the US taking acetaminophen each week, reduced risk perceptions and increased risk-taking could have important effects on society.”

But, what does acetaminophen have to do with risk-taking? Before delving into the results of the three-part study, let’s examine this seemingly strange relationship.

The ‘affect heuristic’

At its core, the effects of acetaminophen on risk-taking may involve the affect heuristic, according to the study authors. The affect heuristic predicts that people rely on mood (ie, affect) as information to guide decision-making, which holds particularly true for risky tasks, activities, and behaviors that are particularly stimulating and engaging.

The affect heuristic also applies to a context of risk and benefit judgments, according to the authors. 

“Individuals appear to rely on affect to infer the risks and benefits offered by activities and hazards. Objects that elicit positive affect, say alcoholic beverages, tend to be judged as having high benefits and low risks,” the authors wrote. “Conversely, objects that elicit negative affect, say nuclear power, tend to be judged as low in benefit and high in risk. Because acetaminophen appears to reduce the extremity of affective reactions to stimuli, it may reduce perceived risk and perceived benefit of a behavior or policy.”

In the face of a complex decision, people often employ their feelings when deciding which option to choose. The affect becomes a cue—in lieu of more taxing probability calculations—thus permitting people to avoid hazards quickly and efficiently. Acetaminophen, a drug that regulates affect, may influence decisions about risk. 

Study 1

In the first double-blind placebo-controlled study, 142 undergraduate students were randomized to receive 1,000 mg of acetaminophen or placebo. To test risk, the participants then engaged in a computer simulation called the Balloon Analog Risk Task (BART). In this exercise, participants made successive decisions to pump a balloon and collected imaginary money each time it inflated without bursting.

At any point, the participants could cash in their money and stop inflating the balloon, or continue inflating the balloon and collecting more money. If the balloon burst at any point, the participants would lose their unbanked winnings. The chances of the balloon bursting went up with each successive inflation. There were 128 possible pumps, with the chances of bursting 1/128 on the first try and 1/1 on the 128th pump.

In Study 1, participants taking acetaminophen took more risk on BART, but acetaminophen did not decrease risk or benefit perceptions. The authors suggested that this second result could be because BART was less exciting than interventions used in previous research.

Study 2

In the second double-blind placebo-controlled study, the researchers used BART to assess risk-taking in 189 students after the participants took either acetaminophen or placebo. The investigators, however, assessed risk and benefits using a different test that analyzed general risk and benefit perceptions, in addition to domain-specific perceptions, including finance, health, recreational, and social domains.

As with the first study, in the second study, researchers found that participants who took acetaminophen took more risk. Additionally, risk perception was decreased, but not benefit perceptions. 

Study 3

In the third study, 215 undergraduate students who took either acetaminophen or placebo were asked to complete two other risk-taking tasks called the Columbia Card Task and the Iowa Gambling Task before completing BART. Although results from these other two tasks still need to be analyzed, the researchers found no significant difference in risk-taking behavior with BART between the acetaminophen and placebo groups. 

In the aggregate the researchers found that acetaminophen may decrease negative affect and risk perception, thus increasing risk-taking. With respect to healthcare and public health, they highlighted a couple of potential scenarios where these findings may apply.

“Many areas of daily life require making decisions that involve the processes examined here. For example, many patients in the hospital have acetaminophen in their systems when presented with risk information and asked to make potentially life-changing risk assessments such as whether or not to do an invasive surgery. Similarly, when driving, one is regularly presented with decisions that involve risk perception and assessment,” they wrote.

In other words, it may be a good idea to consider the effects of acetaminophen (and other drugs) on judgment calls that your patients make in the hospital.

Intriguingly, the authors also pondered whether the inhibition production of prostaglandins in the brain, —which is a general mechanism of NSAIDs—could be responsible for risk-taking behaviors. Alternatively, a separate mechanism specific to acetaminophen could be at play, thus signifying the need for more research. 

Baldwin Way, in the aforementioned Neuroscience News article, points out that acetaminophen is the recommended treatment for initial COVID-19 symptoms by the CDC. “We really need more research on the effects of acetaminophen and other over-the-counter drugs on the choices and risks we take,” he said.

Earlier studies also point to unusual psychological side effects of acetaminophen, including reduced social pain, decreased empathy for others’ pain, and its ability to influence our thoughts and emotions

Other side effects of acetaminophen

In terms of physical side effects, rarely, the ingestion of acetaminophen can result in serious skin reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. These conditions can be lethal. According to the FDA, “Reddening of the skin, rash, blisters, and detachment of the upper surface of the skin can occur with the use of drug products that contain acetaminophen. These reactions can occur with first-time use of acetaminophen or at any time while it is being taken."

Incidentally, other drugs used to treat fever and pain/body aches (eg, nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen) also carry the risk of causing serious skin reactions.  

Share with emailShare to FacebookShare to LinkedInShare to Twitter