Acetaminophen is one of the most commonly used medications for pain relief and fever reduction. It is the most popular over-the-counter means of pain relief in the United States, taken by an estimated 50 million Americans each week (1). When taken at the recommended dosage (4,000 mg per day maximum according to the FDA ,https://www.fda.gov/consumers/consumer-updates/dont-double-acetaminophen), this drug is considered as both safe and effective, and recent studies suggest that low doses of acetaminophen may produce beneficial and neuroprotective effects on the brain (2).
A study by DeWall et al. 2010 examining the effects of acetaminophen on the experience of social pain and underlying brain activity discovered that acetaminophen can at least temporarily alleviate social pain at both neural and behavioral levels (4). Social pain is the experience of pain as a result from interpersonal rejection or loss, such as being bullied or excluded by others. The 2010 study carried out a test where 62 healthy undergraduate participants, 48 women and 14 men, ingested a daily dose of 1,000 mg of acetaminophen or placebo pills each day for three weeks and reported their hurt feelings daily. Each evening, participants used the Hurt Feelings Scale to report how much social pain they experienced that day. Additionally, they provided a daily measure of general positive emotion they had experienced during the same day, also allowing them to test whether acetaminophen alters positive experience. The results suggest that participants’ psychological pain significantly decreased over time for those who took acetaminophen with statistically significant changes observed after 11 days (p < 0.05 compared to placebo group) and highly significant change after 21 days (p < 0.005). Contrastingly, participants who took the placebo displayed no change over time in their everyday hurt feelings. Furthermore, neither the acetaminophen nor placebo group had significant differences over time for daily positive emotion. This data suggests that a low daily dose of acetaminophen can reduce self-reported distress; thus, this drug seems to act on emotions that are associated with decreasing social pain rather than boosting positive emotion.
In another experiment by DeWall et al. 2010, the neural mechanisms by which acetaminophen decreased hurt feelings were investigated (4). Twenty-five healthy undergraduate participants, 16 women and 9 men, took 2,000 mg per day of either acetaminophen or placebo pills for three weeks and completed a social exclusion task while undergoing functional magnetic resonance imaging (fMRI), a technique that measures brain activity. Due to the smaller sample size in this experiment, they doubled the daily dose administered to counteract the decreased statistical power. After the three weeks, subjects completed a virtual ball-tossing game by playing with a computer program to create feelings of social rejection. In the first round of the game, participants were included for the entire duration of the game. In the second round, participants were excluded after receiving the ball three times, and the other two players stopped throwing the ball to them. As a result, they found that participants who took acetaminophen demonstrated significantly less activity than those who took placebo in brain regions that have been linked with physical and social pain processes, including the dorsal anterior cingulate cortex and anterior insula. These experiments suggest that not only does acetaminophen reduce self-reported hurt feelings over time, but it also reduces social-pain related neural responses to social rejection.
Another study explored acetaminophen’s effect on people’s reactivity towards negative and positive stimuli and found that this drug has a general blunting effect on an individual's evaluative and emotional processing (1). In this case, the stimuli were a series of negative and positive images from the International Affective Picture System. In Geoffrey et al. 2015 experiment, 82 participants (it is unclear how many were males or females) was randomly assigned to take either an acute dose of 1,000 mg of acetaminophen or placebo in liquid form. After an hour waiting period for the acetaminophen to enter the brain, the subjects were presented with 40 pictures in random order, where they evaluated the extent of how negative or positive they were and rated their level of emotional reaction to them. The results suggest that participants who took acetaminophen evaluated unpleasant stimuli less negatively and pleasant stimuli less positively, compared with participants who took a placebo. Moreover, participants in the acetaminophen condition rated both negative and positive stimuli as less emotionally arousing (4.21 +/- 1.23 (standard deviation) emotion arousal index for acetaminophen treated and 4.88 +/- 1.29 for placebo treated) than did participants in the placebo condition. The effects of acetaminophen on negative and positive stimuli indicate that acetaminophen-caused neurochemical changes affect more than one psychological evaluative processes.
Although more research is needed to understand neural and physiological levels at which acetaminophen affects people’s feelings, these results imply that this drug can provisionally reduce intense sensitivity towards good and bad situations. However, it is important to note that people should only use acetaminophen when necessary, as acetaminophen has been reported to increase the risk of hepatotoxicity, or serious liver damage (2). If we are experiencing a headache or other forms of pain, then reduced or alleviating that pain will likely cause us to be in a better mood. What the research suggests is that besides the effects of reduced pain on our mood neural responses are affected that are beneficial for our social pain. Overall, taking acetaminophen for pain may have other beneficial effects psychologically, but should be used with caution.
Written by Keira Tam and edited by Aldrin V. Gomes, PhD
References:
Geoffrey R. O. Durso, A. L., Way, B.M. (2015). Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen Blunts Evaluation Sensitivity to Both Negative and Positive Stimuli. Psychological Science. Jun;26(6):750-8. https://journals.sagepub.com/doi/10.1177/0956797615570366.
Ghanem, C. I., Pérez, M.J., Manautou, J.E., Mottino, A.D. (2016). Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. Pharmacological Research. 109. 119-131. https://www.sciencedirect.com/science/article/pii/S1043661816000530#bib0605
Don't Double Up on Acetaminophen. U.S. Food and Drug Administration. Accessed July 13th 2021. https://www.fda.gov/consumers/consumer-updates/dont-double-acetaminophen.
DeWall, C. N., MacDonald, G., Webster, G. D., Masten, C. L., Baumeister, R. F., Powell, C., Combs, D., Schurtz, D. R., Stillman, T. F., Tice, D. M., & Eisenberger, N. I. (2010). Acetaminophen Reduces Social Pain: Behavioral and Neural Evidence. Psychological Science. 21(7), 931–937. https://doi.org/10.1177/0956797610374741
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