The surprising - and disturbing - effects of paracetamol on your mind

Research on the effects of Australia's most widely-taken pain relieving drug on our thoughts, emotions and perceptions has uncovered some disturbing findings.

Paracetamol, also known as acetaminophen, is the most widely-used pain-relieving medication in Australia. Most households across the nation have a pack of Panadol, Panamax, Dymadon or generic paracetamol lurking in their medicine cabinet or bathroom drawer.

Over 1 million tablets/capsules were sold per 10 000 population by community pharmacies alone in 2019 - this figure doesn't take into account the paracetamol purchased in supermarkets and online pharmacies - which averages out to 2 paracetamols per week for every man, woman and child in the country. (And since I never take it, someone's having my share as well!)

While usually touted as a safe and effective pain-reliever, paracetamol is the most common cause of drug overdose in Australia, with over 95 000 hospitalisations (including almost 23 000 intentional overdoses) and 200 deaths attributable to paracetamol occurring in the decade from 2007-2017.

In fact, Australia's drug regulator, the Therapeutic Goods Administration (TGA), recently amended the scheduling of paracetamol in the Poisons Standard, due to concerns about rising rates of attempted and completed suicide using this ubiquitous drug, especially in female adolescents and young women. These schedule amendments reduce the pack sizes that can be sold in both retail and pharmacy settings, and alter packaging to deter impulsive self-poisoning. (Injecting experimental mRNA technology into the entire population is just fine with the TGA, though. Remember - it's Safe and Effective™.)

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The harmful effects of long-term use or overuse of paracetamol on the liver and kidneys are well known, but research on its psychological effects has only begun in the last 10 years. The findings of this research are not included in discussions of the drug's adverse effects (e.g. see here, here and here.)

Astonishingly, although paracetamol was invented in 1893, the mechanism by which it relieves pain is still unclear. Unlike nonsteroidal anti-inflammatory drugs such as ibuprofen, which block pain signals at the site of pain, paracetamol is believed to act on the central nervous system, blocking the intensity of pain signals.

It's these so-called central effects of paracetamol that are also likely responsible for its marked and somewhat disturbing effects on the thought processes and emotional responses of people who take it.

Before digging into the research on these effects, a brief discussion of pain is in order.

Britannica defines pain as

“[A] complex experience consisting of a physiological and a psychological response to a noxious stimulus. Pain is a warning mechanism that protects an organism by influencing it to withdraw from harmful stimuli; it is primarily associated with injury or the threat of injury."

pain

It's important to understand that pain is not felt in the part of the body that (apparently) 'hurts'. As Professor Lorimer Moseley, a clinical scientist investigating pain in humans, explains, all pain is produced in the brain, as a result of its processing of multiple, complex stimuli including input from nociceptors (nerve endings that detect tissue damage), its interpretation of the likelihood of damage, and the social, cognitive and affective (emotional) context of the person experiencing the pain.

And as it turns out, some of the regions of the brain that process physical pain - that is, the response to the threat of physical injury - including the dorsal anterior cingulate cortex and anterior insula, are also involved in the perception of psychological pain - that is, the response to the threat of social or emotional hurt, such as social rejection or loss of a loved one.

Why would this be so? Probably because remaining socially connected to other humans was absolutely critical to our ancestors' survival. Evolution therefore selected for individuals who felt pain when socially rejected, thus motivating them to modify their behaviour in order to avoid upsetting their peers.

Intriguingly, the anterior cingulate cortex is also believed to be involved in the inhibition of behaviour that violates one's religious and political beliefs. In other words, it appears to be integral to the behavioural implementation of one's moral convictions.

All that said, what does the research on the psychological effects of paracetamol actually show?

• In the first study ever published on the effect of paracetamol on non-physical pain, volunteers who took a daily dose of paracetamol for 3 weeks reported less social pain (hurt feelings experienced due to social exclusion) in everyday life, and had reduced activity in regions of the brain that process the affective (emotional) content of pain after experiencing an experimentally-induced episode of social rejection - although they didn't report feeling less social distress after this episode.
  The authors of this study expressed guarded optimism about the potential benefits of the social pain-relieving effect of paracetamol, speculating that it may reduce antisocial behaviour and aggression in response to social rejection. But while reading the study, I couldn't help but wonder whether reduced sensitivity to the pain of social rejection might reflect a decreased awareness of the impact one was having on other people, depriving the individual of the valuable feedback that we all need in order to work cooperatively with others. Furthermore, people who are overly sensitive to rejection feedback would be deprived of the opportunity to learn better coping skills - such as speaking up for one's unpopular stances, or just choosing better friends - if they were able to simply medicate their social pain away.

• Along these lines, a subsequent study confirmed that paracetamol did not relieve generalised anticipatory social anxiety (the kind of nervousness that one might feel before entering a social situation), but only social anxiety that occurred after participants had experienced social rejection that they had not expected. Again, this suggests that paracetamol might impair our capacity to learn from past experiences in order to avoid behaviours that court social rejection.

• Another study found that paracetamol caused participants to reduce their perceptions of risk by decreasing the negative emotions they experienced when contemplating a risky behaviour, and to increase their actual risk-taking behaviour.
  The implications of this altered risk processing were not lost on the authors, who commented:

"With nearly 25% of the population consuming acetaminophen [paracetamol] each week..., reduced risk perceptions and increased risk taking could have important societal effects. 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. Thus, it is imperative that we understand acetaminophen’s effects on choices made and risks taken. Risk perception and risk taking are judgments and decisions that can affect many aspects of our lives, and this common, over-the-counter drug may influence this process, unbeknownst to the millions taking the drug."

Effects of acetaminophen on risk taking

• In a study which examined the effects of paracetamol on existential threat (induced firstly by asking participants to write about what would happen to their bodies after they died and how they felt about that, and secondly by watching a clip from a particularly surrealist David Lynch film), the drug was found to blunt participants' emotional reaction to such threats.
  Again, I had a sense of profound discomfort when reading this study. The capacity to recognise and respond to existential threat is a quintessential element of human experience. To the best of our knowledge, no other animal is capable of thinking about its own death.
  Yet the contemplation of our own mortality is frequently a spur for us to live our lives in ways that truly reflect our values - a fact that I've borne witness to many times, when I speak to clients who have received a diagnosis of cancer or other life-threatening diseases. Many of them express profound gratitude for their diagnosis, explaining that it prompted them to make much-needed life changes such as quitting a soul-sucking job, reconciling with an estranged family member, confronting a cheating spouse, or simply taking time to smell the roses each day. What, I wonder, are the consequences of dampening our ability to feel the profound discomfort which contemplation of our own mortality normally evokes? What beneficial changes in life orientation might be prevented if this discomfort were extinguished by that little white pill that so many people pop, multiple times per week?

• What about paracetamol's effect on our ability to simply feel our own feelings - another foundational experience of humanity? In a study of the effects of paracetamol on participants' emotional reactions to both negative and positive images, those who took the painkilling drug were found to evaluate unpleasant stimuli less negatively and pleasant stimuli less positively. That is,

"These findings suggest that acetaminophen has a general blunting effect on individuals’ evaluative and emotional processing, irrespective of negative or positive valence."

Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen Blunts Evaluation Sensitivity to Both Negative and Positive Stimuli

Well, there's nothing disturbing at all about the idea of a bunch of numbed-out emotional zombies stumbling around in the world, is there?

• Yet another study found that paracetamol reduces people's empathy, personal distress and concern for pain (both physical and social) suffered by others, both when they either imagined people being physically injured or socially hurt, and when they actually witnessed other participants being socially rejected.
  The authors of this study were fully aware of the potential implications of their findings:

"Because empathy regulates prosocial and antisocial behavior, these drug-induced reductions in empathy raise concerns about the broader social side effects of acetaminophen, which is taken by almost a quarter of adults in the United States each week...
Our findings raise important questions about the societal impact of acetaminophen. Empathy for another’s pain and suffering is an important motivator of compassionate actions... Empathic affect and cognition can also serve as brakes on aggressive and hurtful impulses... . Based on the drug-induced reductions in empathy seen here, acetaminophen, and potentially other analgesics, might interfere with social processes that are critical for the promotion of social bonds and social order. Given the millions of people who consume acetaminophen on a regular basis... the social consequences of acetaminophen could be far more costly than previously assumed."

From painkiller to empathy killer: acetaminophen (paracetamol) reduces empathy for pain

• And finally, compared to placebo, people who took paracetamol experienced reduced positive empathy - that is, less feelings of pleasure, delight, and joy - when they read scenarios that described uplifting experiences of other people. These scenarios included having one's beloved accept a marriage proposal, achieving job success, and receiving praise from a parent for one's musical talents. Interestingly, their cognitive assessment of such experiences was unaffected; that is, they judged each scenario as being highly likely to be very pleasurable for the person who experienced it. But they didn't feel those pleasurable sensations when they pictured another person enjoying their successes.
  Once again, the authors of this study had a keen sense of its implications:

"Positive empathy provides part of the ‘social glue’ from which interpersonal bonds are built and strengthened (Morelli et al., 2015). As such, taking pleasure from the good fortune of others fosters interpersonal connection, trust, and – ultimately – prosocial behavior (Reis et al., 2010; Morelli et al., 2014; Andreychik and Migliaccio, 2015), thus providing important societal benefits. These benefits have to be viewed in the context of the amount of people regularly consuming acetaminophen. An estimated quarter of all US American adults take a drug containing acetaminophen every week (Kaufman et al., 2002). It is thus possible that the pervasive use of acetaminophen among Americans may substantially reduce these benefits."

A Social Analgesic? Acetaminophen (Paracetamol) Reduces Positive Empathy

Given the widespread use of paracetamol internationally, its effects on our ability to process our emotions, empathise with others' joy and suffering, learn from negative experiences and accurately assess risk is really quite disturbing.

Pain is a guidance system, directing us to avoid engaging in actions that may damage us physically, emotionally and even spiritually. The pain of a sprained ankle warns us not to bear weight on the affected limb until it has begun to heal. The pain of social rejection warns us not to engage in behaviour that offends and upsets others - or perhaps, to make wiser choices in whom we seek to befriend. Imagining the pain of other people helps us to relate to them, and reduces the risk of dangerous 'othering' of fellow humans who may differ from us in appearance, beliefs or practices. Existential pain prompts us to consider whether we're making life choices that align with our deepest values.

As German philosopher Thomas Metzinger put it,

"Functionally speaking, suffering is necessary for autonomous self-motivation and the emergence of truly intelligent behaviour."

Suffering, the cognitive scotoma

While short-term use of paracetamol is clearly warranted in certain circumstances - for example, for severe post-operative pain - frequent use may thwart our ability to respond appropriately to potential dangers in our lives, and even degrade our capacity for some of the most fundamental experiences of being human - emotional response, empathy for others, and existential threat.

Final note:

If you use paracetamol/acetaminophen when you have cold or flu-like symptoms, or you give it to your children when they are feverish, you should also read my articles Amusing COVID-19 patients to death with fever suppressing drugs and The medical insanity of fever suppression in COVID-19. Suppressing fever during an acute infectious illness is one of the most stupid, dangerous and counterproductive actions that you could possibly take. And if you want to know how to manage fever intelligently, sign up for my full-day Be Your Own Doctor seminar. In-person and virtual attendance options are available.

For information on my private practice, please visit Empower Total Health. I am a Certified Lifestyle Medicine Practitioner, with an ND, GDCouns, BHSc(Hons) and Fellowship of the Australasian Society of Lifestyle Medicine.