Tylenol Treats the Blues

Jacob Schor, ND, FABNO


May 15, 2013



New research suggests that over the counter acetaminophen, the ingredient in Tylenol, may reduce existential pain.


Daniel Randles and colleagues at the University of British Columbia, reported in the journal Psychological Science that Tylenol may have a profound psychological effect.

We often speak of psychological distress as pain but most of us would not have thought a painkiller would bring relief.


But according to Randles, "Pain extends beyond tissue damage and hurt feelings, and includes the distress and existential angst we feel when we're uncertain or have just experienced something surreal. Regardless of the kind of pain, taking Tylenol seems to inhibit the brain signal that says something is wrong."


How one creates and measures existential pain in test subjects is a bit complex.

Earlier research had already shown that when the order, and meaning in life is threatened, possibly by thoughts of death, most people reassert their basic values as a way to cope. That is they become moralistic.


In 2010 Dewall et al reported that both physical and social pain are alleviated by acetaminophen.[1]         Apparently physical pain and emotional pain share a common neural pathway. Numb the pathway and you numb both pains.[2] Randles wondered whether existentialist suffering triggered by thoughts of death might involve similar brain processes.


Study participants took either Tylenol brand acetaminophen or placebo in a double-blinded study. One group of participants was asked to write an essay about what would happen to their body after they die. The second group wrote about dental pain, which while unpleasant rarely leads to existential dread.


Both groups then read an arrest report about a prostitute, and were asked to set her bail amount. Those who wrote about dental pain, set the bail low, about $300.


Those participants who wrote about their own deaths and had taken the placebo and were suffering from non-palliated existential discomfort set the bail amount at $500, about 40% higher. Asserting basic values, in this case punishing the prostitute, is considered a coping mechanism. The death essay group that took Tylenol did not increase the bail amount.              Taking the Tylenol apparently treated the existential angst and this subgroup did not need to assert their values.


Randles confirmed this concept in a second study that used video clips. Study participants who watched a video of spectators rioting at a hockey game (these are Canadian studies) who had taken a placebo judged the rioters more harshly than those who took a Tylenol first. Who would have thought that taking a Tylenol could cure the discomfort triggered by watching an unsettling movie? [3]


"We're still taken aback that we've found that a drug used primarily to alleviate headaches can also make people numb to the worry of thinking about their deaths…." says Randles.


There are no shortages of emotionally painful experience in life. Could the solution be so simple as to pop a dose of Tylenol? Acetaminophen, as many of my readers will be quick to remind me, is not without its downsides.


I discussed the dangers of acetaminophen at length in a newsletter half a dozen years ago.




Simply put, the drug acetaminophen, what we call Tylenol, is the leading cause of acute liver failure in our country. William Lee writing in the December 2005 issue of Hepatology summarized the data. Of the 275 people with acetaminophen poisoning, 8% received a liver transplant, 65% survived without one and 27% died. Although accidental poisonings outnumber suicide attempts 48% to 44%, rate of survival didn’t differ.            Although we talk about it and take it as if it were a safe drug, it is far from it. Taking even slightly more than the suggested dose is risky.


Prior to 1980 the link between acetaminophen and liver failure was unknown. This knowledge hasn’t discouraged use. Between 1998 and 2003, the proportion of cases of liver failure caused by the drug nearly doubled.


Many of the people who had accidentally poisoned themselves did so by taking just 10 grams of the medication each day for about three days - the equivalent of about 20 pills per day instead of the recommended eight.


Increasing gluathione levels in the body can reduce the danger of acetaminophen toxicity. The classic method is to give n-acetyl-cysteine as it may lower risk of poisoning.[4]




Talk about existential angst. We have the solution for emotional pain, only if we use it just a bit too freely, we could end up dead.        


Could other perhaps safer pain killers also reduce our emotional discomfort?


Perhaps if we knew exactly how acetaminophen worked we could use other safer things with a similar target of action. The problem is that the mechanism of action of acetaminophen is not completely understood. Though it’s still debated the main mechanism is currently thought to be the inhibition of cyclooxygenase (COX), in particular COX-2. [5]


Well gosh, lots of natural things appear to hinder COX-2. Curcumin is the first that comes to mind. The most recent paper out of well over a hundred was published a few days ago. Hu et al describe how periodontal disease stimulates production of COX-2 enzymes and how curcumin inhibits the increased production.[6]

This is different from acetaminophen, which blocks the function of existing COX-2 enzymes. While lots of patients like curcumin because it reduces painful inflammation, I can’t recall anyone commenting that it reduced their emotional angst.

Frankincense is also used to fight inflammation but it seems that its active constituent, boswellic acid, inhibits COX-1 rather than CO-2. [7]    

In a November 2012 paper, Scoditti et al remind us that many of the polyphenols found in significant quantities in the Mediterranean diet are COX-2 inhibitors. [8] That would suggest people adhering to such a diet might experience less emotional pain or existential angst.


Kind of easy gong, relaxed, enjoying life more, and free of existential angst……think about it, isn’t that the image we already have of Mediterranean cultures? In the end maybe it’s all about what they eat.







1. Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF,Tice DM, Eisenberger NI. Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 2010 Jul;21(7):931-7. doi: 10.1177/0956797610374741. Epub 2010 Jun 14.


2. Eisenberger NI, Lieberman MD. Trends Cogn Sci. 2004 Jul;8(7):294-300. Why rejection hurts: a common neural alarm system for physical and social pain.


3. Randles D, Heine SJ, Santos N. The Common Pain of Surrealism and Death: Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats. Psychol Sci. 2013 Apr 23. [Epub ahead of print]


4. Kolacinski Z , Rusinski P. [Paracetamol: therapeutic action, pathogenesis and treatment of acute poisonings complicated by severe liver damage]. Przegl Lek. 2003;60(4):218-22.


5. Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J. 2008 Feb;22(2):383-90. Epub 2007 Sep 20.


6. Hu P, Huang P, Chen MW. Curcumin attenuates cyclooxygenase-2 expression via inhibition of the NF-κB pathway in lipopolysaccharide-stimulated human gingival fibroblasts. Cell Biol Int. 2013 May;37(5):443-8.


7. Siemoneit U, Hofmann B, Kather N, Lamkemeyer T, Madlung J, Franke L, Schneider G, Jauch J, Poeckel D, Werz O. Identification and functional analysis of cyclooxygenase-1 as a molecular target of boswellic acids. Biochem Pharmacol. 2008 Jan 15;75(2):503-13. Epub 2007 Sep 14.


8. Scoditti E, Calabriso N, Massaro M, Pellegrino M, Storelli C, Martines G, De Caterina R, Carluccio MA.Arch Biochem Biophys. 2012 Nov 15;527(2):81-9. Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer.