OTC Pain Medication Is Being Studied for the Relief of Emotional Pain

Is There a Case To Be Made for OTC Pain Medication Use as an Anxiolytic?

A friend mentioned this to me in passing not too long ago, and it got me wondering if there is anything substantive to the claim. After all, it’s all too common nowadays to be frequently bombarded with sensational claims and shameless clickbait to articles based solely on in vitro and rodent studies. I figured this would be a good opportunity and use-case (excuse) for trying out ChatGPT’s Deep Research feature. This is what it had to say on the topic.

Research over the past two decades supports the idea that physical pain and social or emotional pain share overlapping neural mechanisms. In particular, the brain’s “pain matrix” involved in the affective distress of physical pain – notably regions like the dorsal anterior cingulate cortex (dACC) and anterior insula – also activates during experiences of social rejection or emotional loss​pubmed.ncbi.nlm.nih.gov. This pain overlap theory suggests that the “hurt” of social or existential distress may piggyback on some of the same neural pathways as bodily pain ​pubmed.ncbi.nlm.nih.gov. If so, medications that dull physical pain could similarly blunt emotional pain or anxiety signals. Indeed, multiple human studies have explored whether common over-the-counter (OTC) analgesics (like acetaminophen and NSAIDs such as ibuprofen) alter people’s emotional responses – from anxiety and social anguish to discomfort in decision-making. Below we review key findings, proposed mechanisms, and cautions from this emerging research.

Acetaminophen’s Effects on Anxiety, Social Pain, and Avoidance

Acetaminophen (paracetamol) – the active ingredient in Tylenol – is a centrally-acting analgesic that reduces physical pain and fever without strong peripheral anti-inflammatory action. Because it acts in the brain, researchers reasoned it might also dampen the neural alarm signals of emotional pain ​pubmed.ncbi.nlm.nih.gov​healthline.com. A landmark placebo-controlled study in 2010 found that taking acetaminophen daily for three weeks led to lower self-reported “hurt feelings” in healthy volunteers, and fMRI scans confirmed reduced activity in the dACC and insula during a social rejection task (Cyberball) compared to placebo​pubmed.ncbi.nlm.nih.gov. In other words, acetaminophen seemed to reduce both the emotional pain of social rejection and the typical brain response to that pain​pubmed.ncbi.nlm.nih.gov. This provided initial evidence that an OTC painkiller can blunt social anguish, bolstering the idea of shared neural pathways for physical and social pain.

Subsequent experiments extended these findings to other forms of anxiety and psychological discomfort. In one study at the University of British Columbia, participants took 1000 mg of acetaminophen or placebo and were subjected to unsettling experiences designed to provoke existential anxiety – for example, writing about their own death or watching a surreal David Lynch film ​medicalnewstoday.com​medicalnewstoday.com. Remarkably, those who had taken acetaminophen showed less anxiety and distress in response to these existential challenges. They set lower bail/punishment for hypothetical criminals after contemplating mortality (a measure of reduced harsh judgment under threat) and were less punitive after watching the disturbing film ​medicalnewstoday.com. The researchers concluded that the acetaminophen group was “numbed” to the anxiety of thinking about death or confronting something deeply unsettling, relative to placebo​medicalnewstoday.com. In effect, the existential dread that normally causes psychological pain was partially alleviated by the physical painkiller​medicalnewstoday.com. These findings were reported as evidence that an OTC drug for headaches might also “inhibit the brain signal that says something is wrong” during social or existential threat ​medicalnewstoday.com​medicalnewstoday.com. Consistent with this, a media summary noted “acetaminophen, even in a non-prescription dose, dulls feelings of anxiety and psychological responses to questions about life and death” ​healthline.com – essentially taking the “edge” off existential anxiety. Importantly, the acetaminophen group’s muted emotional reaction was linked to limiting activation in brain regions like the dACC that register a sense of alarm​healthline.com​healthline.com.

Acetaminophen’s ability to reduce social pain and anxiety appears not limited to extreme scenarios. In everyday decision-making, people often experience an aversive mental tension (a “pain of decision”) when choosing between two desirable options or when facing potential losses. This discomfort can lead to avoidance behaviors or biased thinking (e.g. rationalizing a choice to ease cognitive dissonance). Intriguingly, acetaminophen seems to mitigate that discomfort. In one experiment, after taking 1000 mg of acetaminophen or placebo, participants had to make a difficult choice between two options they initially liked. Normally, people cope with the dissonance of rejecting a liked option by later downplaying how good the rejected option was (a classic post-decision rationalization). But with acetaminophen on board, participants showed significantly less of this attitude change, suggesting they felt less inner “pain” from the decision ​kellercenter.hankamer.baylor.edu. Essentially, they didn’t need to avoid or rationalize the uncomfortable choice as much, implying the psychological stress of the decision was reduced​kellercenter.hankamer.baylor.edu. In a related task, acetaminophen also diminished loss aversion – participants who were given a small gift (a coffee mug) set lower selling prices for it if they had taken Tylenol, indicating less emotional discomfort at the prospect of parting with a possession​kellercenter.hankamer.baylor.edu. Together, these studies by DeWall and colleagues suggest acetaminophen can reduce anxiety-like responses in decision-related tasks, smoothing over the negative arousal that often drives avoidance or irrational choices ​kellercenter.hankamer.baylor.edu​kellercenter.hankamer.baylor.edu.

Other research finds that acetaminophen produces a more general “blunting” of evaluative and affective processing in the brain. In controlled trials, acetaminophen not only reduced negative feelings (social pain, fear, frustration) but also toned down positive emotions in some contexts​pmc.ncbi.nlm.nih.gov. For example, DeWall et al. noted it dampened reactions to both negative and positive stimuli, hinting that the drug might broadly inhibit emotional extremes​pmc.ncbi.nlm.nih.gov. A 2015 study by Durso et al. indeed found people on acetaminophen had a narrower range of emotional response to pleasant and unpleasant images, relative to placebo​pmc.ncbi.nlm.nih.gov. In line with this, an EEG experiment (Randles et al. 2016) showed Tylenol specifically reduced the brain’s conscious response to errors. Participants performed a Go/No-Go task; those on acetaminophen had a smaller “error-related positivity” (Pe) in their brainwaves after making mistakes, even though the early automatic error signal (ERN) remained intact​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov. In practical terms, they noticed their mistakes less or cared less about them, which correlated with making more cautious errors later ​pmc.ncbi.nlm.nih.gov. This supports the idea that acetaminophen causes a widespread blunting of evaluative processing – our brain’s flagging of “something is wrong” is muted ​pmc.ncbi.nlm.nih.gov. Such blunting could reduce anxiety-driven behaviors like hypervigilance or error avoidance, but it might also have downsides in dampening normal emotional sensitivity.

Indeed, researchers caution that acetaminophen’s psychological effects are double-edged. While it may take the sting out of social pain or anxiety, it can also “numb” other empathetic or affective responses. For instance, one study found that when people on acetaminophen read about someone else’s misfortunes or physical pain, they rated the other’s pain as less severe and showed lower empathy, compared to those on placebo ​pmc.ncbi.nlm.nih.gov. The painkiller that eases your own hurt feelings may unintentionally make you less sensitive to others’ pain ​pmc.ncbi.nlm.nih.gov. Additionally, by lowering risk perception and anxiety, acetaminophen can lead to increased risk-taking behavior. A series of trials in 2020 showed that college students on 1000 mg acetaminophen took more risks in a balloon-pumping game and perceived less danger in various hypothetical scenarios​pubmed.ncbi.nlm.nih.gov. The effect was subtle but consistent: Tylenol users were less fearful of negative outcomes, which statistically explained their bolder behavior​pubmed.ncbi.nlm.nih.gov. In short, acetaminophen seems to diminish the emotional “braking system” that normally causes hesitation or avoidance of potential harm. While this can manifest as reduced anxiety, it might also encourage imprudent choices or dampen healthy concern. These findings underscore that any “anxiolytic” effect of acetaminophen is not targeted – it comes as part of a broader blunting of affect and evaluative thought ​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov.

Proposed Mechanisms: Acetaminophen’s exact neurochemical mechanism remains somewhat enigmatic, but several clues exist. Unlike NSAIDs, it doesn’t mainly act by peripheral anti-inflammation – instead it influences the central nervous system. Some studies suggest acetaminophen’s metabolite (AM404) increases endocannabinoid activity in the brain and spinal cord​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov, which could produce calming or analgesic effects (the endocannabinoid system helps regulate pain and mood). Acetaminophen may also enhance serotonergic signaling in the cortex ​pmc.ncbi.nlm.nih.gov, and at higher doses it affects TRPV1 receptors involved in pain perception ​pmc.ncbi.nlm.nih.gov. These actions, combined with its impact on brain regions like the ACC, could explain why it dampens the “alarm” response to both physical and social threats. One hypothesis is that acetaminophen reduces the salience of error or threat signals generated in the ACC/insula, thereby reducing the emotional intensity of pain (physical or social) ​pubmed.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov. Supporting this, the UBC studies explicitly found evidence that an OTC dose of acetaminophen limited neural reactivity in the dACC during anxiety-provoking tasks ​healthline.com​healthline.com. In animal research, acetaminophen has shown antidepressant-like effects via the opioid system (in mice, very low doses produced antidepressant behavior that could be blocked by opioid antagonists) and pro-social effects via endocannabinoids​ pmc.ncbi.nlm.nih.gov. For example, one mouse study found acetaminophen increased social interactions in normally asocial mouse strains, paralleling how it reduced social pain in humans​pmc.ncbi.nlm.nih.gov. Taken together, these findings suggest acetaminophen taps into brain pathways (opioid, endocannabinoid, serotonergic) that modulate both pain and mood – effectively dulling the emotional “ouch” that otherwise promotes anxiety and avoidance.

Ibuprofen and Other NSAIDs: Mixed Findings on Anxiety Relief

Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin, and naproxen are another major class of OTC pain relievers. NSAIDs primarily reduce pain by inhibiting cyclooxygenase (COX) enzymes and thus prostaglandin production (lowering inflammation). Because of the growing evidence connecting inflammation with mood disorders, and the overlap of pain/emotion neural circuitry, scientists have explored whether NSAIDs might have anxiolytic or antidepressant effects as well ​journals.plos.org​pmc.ncbi.nlm.nih.gov. The results so far are mixed and sometimes surprising, often depending on the specific drug and population.

Ibuprofen and Social Pain – a Gender Paradox

Initial laboratory studies suggested that, like acetaminophen, ibuprofen could ease emotional pain – but one double-blind trial found a striking sex difference. In this study, 138 young adults were randomly given 400 mg ibuprofen or placebo and then put through social stress scenarios​news.utexas.edu​news.utexas.edu. Women who took ibuprofen reported significantly less hurt feelings when they were socially excluded (in a virtual ball-toss game) and when recalling a painful betrayal, compared to women on placebo ​news.utexas.edu​news.utexas.edu. This implies ibuprofen buffered emotional pain for females, consistent with the idea of a social analgesic. However, men showed the opposite trend – men given ibuprofen actually reported more distress and harsher feelings of rejection in the same scenarios​news.utexas.edu​news.utexas.edu. In other words, the painkiller that soothed women’s feelings appeared to exacerbate men’s feelings of social pain. The lead researcher, Anita Vangelisti, speculated that perhaps men normally suppress or reframe hurt feelings, but ibuprofen might interfere with that coping mechanism ​news.utexas.edu. One idea is that by reducing the physical pain signals, ibuprofen freed up men’s cognitive resources to fully feel and express emotional pain that they’d otherwise bottle up​ news.utexas.edu. Women, on the other hand, may generally ruminate more on social pain, so reducing the pain signal simply provided relief. This gender-specific effect highlights that the relationship between analgesics and emotion is complex – factors like sex, socialization, or hormones could modulate outcomes. It also serves as a caution that an OTC drug might not uniformly reduce anxiety or hurt feelings in everyone (in some cases it could even worsen emotional upset, as seen in men here). More research is needed to understand why these differences occur, but it underscores that ibuprofen’s psychological impact is not one-size-fits-all ​news.utexas.edu​news.utexas.edu.

Outside of the lab, evidence for ibuprofen’s mood effects is inconclusive. Large-scale observational data have hinted at potential benefits – for example, one epidemiological study found regular ibuprofen use was associated with a lower risk of needing psychiatric treatment for mood disorders ​pmc.ncbi.nlm.nih.gov. And some clinical trials with depressed patients (often using prescription-strength NSAIDs or adding NSAIDs to antidepressants) have reported improved symptoms, attributing this to reduced neuro-inflammation ​journals.plos.org​pmc.ncbi.nlm.nih.gov. However, other trials are mixed or negative, and it’s unclear if ibuprofen itself has a direct anti-anxiety effect in healthy people. A small 2021 fMRI study in healthy volunteers saw ibuprofen (200–600 mg) reduce activity in certain brain regions during emotional face processing, but it did not significantly affect self-reported mood in the short term ​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov. Intriguingly, this study also examined a pathway called PPAR-γ (which ibuprofen can activate) and found separate brain effects from PPAR-γ vs. ibuprofen, suggesting any mood-related benefit of ibuprofen might involve multiple mechanisms ​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov. Overall, while ibuprofen shows some promise in dampening emotional reactivity (especially in women), its effects are not as well-demonstrated or consistent as acetaminophen’s in experimental settings. Furthermore, unlike acetaminophen, ibuprofen’s primary mode is anti-inflammatory; if emotional pain doesn’t have an inflammatory component, ibuprofen may have less impact unless other pathways (like PPAR-γ or central prostaglandin reduction) come into play​pmc.ncbi.nlm.nih.gov.

Aspirin, Naproxen, and Other NSAIDs

For other common NSAIDs such as aspirin (acetylsalicylic acid) and naproxen (Aleve), direct experimental research on anxiety or social pain is relatively sparse. However, interest in these drugs’ psychotropic potential has grown due to links between inflammation and mental health. Aspirin, for example, has been investigated in depression: a few trials adding low-dose aspirin to antidepressant therapy found modest improvements in depressive symptoms, and long-term cohort studies noted lower depression incidence in people taking daily aspirin ​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov. These mood benefits are thought to result from aspirin’s anti-inflammatory and possibly neuroprotective properties ​pmc.ncbi.nlm.nih.gov​journals.plos.org. It’s conceivable that by damping inflammation-related signaling (cytokines like IL-6, which can induce anxious mood), aspirin could indirectly reduce anxiety in certain contexts. In one experiment, a single dose of aspirin blunted the usual spike in inflammatory IL-6 after an acute stress, pointing to a mechanism by which it might reduce stress-related mood effects ​sciencedirect.com. That said, there isn’t clear evidence that taking aspirin acutely will calm someone’s nerves the way a fast-acting anxiolytic would – any effect is likely subtle and tied to longer-term inflammatory states.

An intriguing insight comes from a 2018 big-data analysis of FDA adverse event reports, which looked at mood and anxiety outcomes in patients taking various NSAIDs for pain. The study found that not all NSAIDs are equal in their psychiatric effects. Notably, naproxen, along with diclofenac and ketoprofen (two NSAIDs typically used for arthritis), showed significant associations with reduced anxiety and depression reports, whereas others like ibuprofen, aspirin, and celecoxib did not ​journals.plos.org​journals.plos.org. The authors even coined the term “AA-NSAIDs” (anxiolytic–antidepressant NSAIDs) for the three drugs that stood out, suggesting they might have unique pharmacological actions beyond general COX inhibition ​journals.plos.org​journals.plos.org. For example, naproxen readily crosses the blood-brain barrier and might influence serotonin or other neurochemical systems differently than ibuprofen ​journals.plos.org. However, this was a retrospective finding – essentially a correlation in large datasets – so it must be interpreted with caution. It does raise the possibility that naproxen could have some anti-anxiety property in the context of chronic pain management ​journals.plos.org. People taking naproxen for pain might have reported fewer anxiety or depression symptoms than those taking other NSAIDs, hinting at a beneficial effect ​journals.plos.org. On the flip side, the same analysis warned that some NSAIDs (notably aspirin, ibuprofen, and celecoxib) were associated with worse mood/anxiety outcomes in those databases ​journals.plos.org. This doesn’t mean those drugs cause anxiety – it could be that they were often used in situations of greater pain or stress – but it underscores that any mood-related effects of NSAIDs are likely drug-specific. To truly know if, say, naproxen can reduce anxiety or avoidance behavior, we would need controlled trials in humans (none of which have been prominently reported as of yet).

In summary, among OTC analgesics acetaminophen has the clearest evidence of blunting anxiety, social pain, and related aversive feelings in the short term. NSAIDs show a more variable pattern: ibuprofen can relieve social pain in some cases (with interesting gender differences), and epidemiological or adjunct-treatment studies hint that certain NSAIDs (naproxen, diclofenac) might have mood-improving effects in contexts of pain and inflammation ​journals.plos.org​journals.plos.org. These effects are hypothesized to stem from the drugs’ anti-inflammatory action (reducing inflammatory cytokines that drive depression/anxiety) or other central mechanisms (e.g. PPAR-γ activation by ibuprofen, or unique brain penetrance of naproxen) ​journals.plos.org​pmc.ncbi.nlm.nih.gov. Still, the research on NSAIDs for anxiety is relatively nascent and sometimes contradictory.

Limitations and Cautions

While the notion of “painkillers for the pain of the psyche” is fascinating, scientists urge caution in interpreting these results. First, the magnitude of the effects in studies is generally modest. These medications are not comparable to dedicated psychiatric drugs in potency; rather, they cause subtle shifts in how people experience distress or make judgments under lab conditions. For example, acetaminophen’s impact on social pain or anxiety is significant but not dramatic – it won’t erase heartbreak or cure an anxiety disorder, and not every study finds an effect ​tandfonline.com. In fact, a recent experiment failed to replicate acetaminophen’s blunting of social rejection in terms of subjective feelings (though brain measures weren’t affected) ​tandfonline.com, suggesting context matters.

Secondly, self-medicating with OTC analgesics for anxiety is not an established or recommended practice. These drugs carry well-known physical risks if overused: acetaminophen can damage the liver at high doses or with chronic use, and NSAIDs can cause gastrointestinal bleeding, kidney strain, or cardiovascular issues. The studies discussed typically used short-term dosing in controlled settings. Relying on daily Tylenol or ibuprofen to cope with stress could lead to health problems without addressing the underlying causes of anxiety. Moreover, as described, blunting one’s emotions pharmacologically can have downsides. Important positive emotions may be dulled along with the negative ​pmc.ncbi.nlm.nih.gov. For instance, consistently numbing your distress might impair learning from mistakes or empathy toward others ​pmc.ncbi.nlm.nih.gov. One tongue-in-cheek headline called acetaminophen an “empathy killer” as much as a pain killer, because it made people less emotionally attuned ​pmc.ncbi.nlm.nih.gov. Judgment and risk assessment might also be skewed – a person who habitually takes an analgesic to “take the edge off” could become too carefree about genuinely risky choices ​pubmed.ncbi.nlm.nih.gov. These side effects on one’s social and cognitive functioning are subtle, but worth considering.

Another limitation is that these findings may depend on individual differences (such as gender, personality, or baseline inflammation levels). The ibuprofen study clearly showed opposite effects by sex ​news.utexas.edu​news.utexas.edu. Other work suggests personality traits like forgiveness can modulate how well acetaminophen eases social pain over time​neurosciencenews.com. This means we shouldn’t assume an OTC pain med will reliably reduce anxiety for everyone, or in every situation. Context matters – e.g., acetaminophen might help with the “sting” of rejection or existential angst in the moment ​medicalnewstoday.com, but it’s not addressing complex anxiety disorders that involve chronic worry or trauma.

Finally, researchers emphasize that these studies “uncovered yet another use for Tylenol” in a theoretical sense, but they do not suggest using it clinically as an anxiolytic ​healthline.com. More research is needed to fully understand mechanisms and to ensure safety in broader applications. Some trials are exploring anti-inflammatory drugs as adjunctive treatments in depression or anxiety, but results have been mixed ​pmc.ncbi.nlm.nih.gov​journals.plos.org. At present, the consensus is that while the mind effects of OTC pain relievers are real, they are an interesting window into brain processes rather than ready-to-use remedies for anxiety. As one author put it, “these findings won’t result in an acetaminophen-based anti-anxiety medication any time soon”, but they “uncovered yet another use for Tylenol” in understanding the pain of social disconnection ​healthline.com. In practical terms, anyone considering taking these medications for emotional reasons should be aware of the off-label nature and the potential risks. It’s an area to watch, but not a substitute for standard anxiety treatments at this time​medicalnewstoday.com.

Conclusion

In summary, a growing body of evidence indicates that OTC analgesics can have subtle but meaningful cognitive effects beyond just relieving aches. Acetaminophen in particular has been shown to reduce the intensity of negative emotions such as social hurt feelings, anxiety about one’s existence, or the discomfort that leads to task avoidance in decision-making​ pubmed.ncbi.nlm.nih.gov​medicalnewstoday.com. These effects are thought to arise because the drug dampens neural responses in regions like the ACC that underpin both physical pain and emotional distress​pubmed.ncbi.nlm.nih.gov. NSAIDs like ibuprofen, aspirin, and naproxen have been less studied in this domain, but early findings suggest some overlap with mood regulation – for instance, ibuprofen eases social pain in women (but not men) ​news.utexas.edu, and certain NSAIDs might confer anti-anxiety or antidepressant benefits in contexts of high inflammation or pain​journals.plos.org​journals.plos.org. The proposed mechanisms include anti-inflammatory actions reducing inflammatory cytokines that can drive anxiety, and direct brain effects (such as PPAR-γ activation or endocannabinoid modulation) altering emotional neural circuits ​journals.plos.org​pmc.ncbi.nlm.nih.gov.

Crucially, these discoveries come with important caveats. The emotional blunting from analgesics is non-discriminatory – while it can take away some pain of social rejection or fear, it may also take away some joy or empathy ​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov. The research is still in its infancy and mostly involves short-term experiments with healthy people; we lack long-term studies on using OTC pain meds for anxiety or avoidance behavior. Nevertheless, this line of work has yielded key insights: it strengthens the theory that social and physical pain share neural roots, and it opens intriguing questions about how the most common drugs in our medicine cabinets quietly influence our minds. As one paper aptly titled it, acetaminophen might function as a “social analgesic,” blunting the sting of not just a stubbed toe but also a stubbed ego ​healthline.com​healthline.com. Going forward, researchers are continuing to unravel these connections, which could one day inform novel approaches to managing the entwined experience of physical and emotional pain – but for now, the recommendation is to approach with caution and appreciate that even humble painkillers can have psychological effects beyond what we intend ​medicalnewstoday.com.

Sources: Research findings and quotations are drawn from peer-reviewed studies and reviews, including DeWall et al. (2010) on acetaminophen and social pain​ pubmed.ncbi.nlm.nih.gov, Randles et al. (2013) on existential anxiety ​medicalnewstoday.com​medicalnewstoday.com, DeWall et al. (2015) on decision-making pain ​kellercenter.hankamer.baylor.edu, Keaveney et al. (2020) on risk-taking ​pubmed.ncbi.nlm.nih.gov, and Vangelisti et al. (2014) on ibuprofen’s sex-dependent effects​ news.utexas.edu​news.utexas.edu. Additional insights on mechanisms and limitations come from neuroscience studies (e.g. Randles et al. 2016 EEG study ​pmc.ncbi.nlm.nih.gov) and large-scale analyses of NSAIDs and mood ​journals.plos.org​journals.plos.org.