
What's Tylenol Doing to Our Minds? - BruceM
http://www.theatlantic.com/health/archive/2013/04/whats-tylenol-doing-to-our-minds/275101/
======
DanBC
It is pleasing to see error bars on a graph in a mainstream publication. It's
very nice to have them saying that the study was small and there are more
questions to be asked.

It's good that they mentioned the severe toxicity of paracetamol in overdose.
It does kill many people, and it's not a pleasant death. It also accounts for
many organ transplants.

It would have been nice if they'd said that, taken carefully and with no over
dose, paracetamol is a very safe and very effective medication. It's very
cheap. (At least here in the UK, I found it bafflingly expensive in the US.)

Cultural note: In the UK most medication is dispensed in blister packs. You
can buy paracetamol off the shelf but you can only get limited quantities.
Most shops will only sell you 16 tablets (at 500 g each) or 32 if you buy it
from a person. You can get 100 if you see a pharmacist and persuade them you
need them, but that'll be a struggle in most places. You can get large amounts
if you have a prescription. 16 tablets at 500 g each would cost around £0.20
(for budget pills). Blister packs was an effective suicide control measure,
reducing the number of pills taken and the number of overdoses attempted.
Reduced quantities of pills sold had an initial success in reducing suicide
rates, but number have since risen. Pills in the homes of old people are
especially dangerous. This is because they're not locked away, and young
children visiting sometimes take the pills. And also because suicide rates
among old people are depressingly high.

~~~
gambiting
To be honest, I find the UK law to be absolutely stupid in this regard. I
needed to buy 10 packs of paracetamol, and at local morrisons I was told I
couldn't, maximum was 2 packs(16 tablets each). So I bought two packs, went
out of the store, came back in, bought another two, repeated the process 5x
and got my ten packs. The whole law is just an annoyance, nothing else. If I
wanted to kill myself with paracetamol I could easily get even a 1000 tablets,
would just need to drive around a few supermarkets but this law would not stop
me from doing it.

~~~
Osmium
> The whole law is just an annoyance, nothing else.

This is not true. It's about preventing impulsive suicides, not premeditated
ones. If a depressed person is having an episode and all they have in their
house is 16 pills, then it removes the opportunity: maybe by the time they've
make it to the shops and buy more, the moment will have passed, and a life
would be saved.

It's been shown time and time again that you can reduce absolute suicide rates
by removing opportunities like this. If I remember correctly, there was
something similar involving gas ovens, though I can't find the reference now.
Guns, bridges, etc. are all similar too.

When it comes down to it, if someone's determined enough to kill themselves,
they will, but the truth is _most people aren't_ and doing things like only
selling small quantities of pills really can prevent suicides.

~~~
robbiep
BBC article following reductions in successful suicides (interestingly it says
no reduction in number of overdoses. But we have a pretty good reversal for
paracetamol-induced overdose - N-acetyl-Cystine - so they should have a pretty
good recovery)

<http://www.bbc.co.uk/news/health-21370910>

~~~
DanBC
Yes, but it's very important that anyone with an overdose gets treatment _as
soon as possible_ , even if they feel no ill effects at that time.

Death from paracetamol overdose is by liver failure, and that takes a week or
so to happen, but after the first 24 hours there's not much you can do to
prevent it apart from liver transplant.

Paracetamol overdose is a small number of liver transplants in the UK, but a
significant number of the 'super urgent' transplants.

------
tokenadult
As usual in threads on topics like this, you can rely on HN participant
carbocation's comments for some thoughtful perspective on the original
article.

As the submitted article notes, responding to the press releases by the study
authors,

"This all raises more questions than it answers. This study was small. The
headlines are grandiose. The way people pass moral judgements is not
necessarily indicative of their level of existential anxiety."

Indeed. This is an intriguing issue to study, and well worth some further
studies by other investigators to see if the results will be replicated in
other study populations, but the author of the submitted article was correct
to have a headline with an open-ended question rather than a definitive
statement about Tylenol. On my part, because I take different over-the-counter
pain relief medications when I need any of those, I'm curious if this result
would be replicated for aspirin or for ibuprofen. That the pain of stubbing a
toe and the pain of rejection in love might have some of the same brain
mechanisms is suggested by our use of the word "pain" for both phenomena. But
that requires further study. (I'm sure there are many studies already on that
issue, but I'm not deeply familiar with the research literature on that
topic.) That pain (of either kind) might motivate action and thus dulling pain
might reduce motivation for some actions is also plausible, and also has
surely been investigated before, but perhaps there are still some very basic
facts about that issue yet to be discovered. As so often happens after a new
study is published, the most firm conclusion is "further research is needed."

~~~
rcthompson
Tylenol has a different mechanism than most other over-the-counter pain
relievers. Most other OTC pain relievers are "non-steroidal anti-inflammatory
drugs" (NSAIDs), which means that they actually reduce inflammation at the
site of injury instead of just reducing the amount of pain that your brain
feels (though they do that too). But I still wouldn't be surprised if they had
similar emotional effects.

~~~
redwood
Good point. It's hard to see the experience of specific pain as ever existing
within a vacuum of human experience.

It's interesting to compare ourselves: a population of pill poppers at the
slightest twinge, to those in other parts of the world who simply don't.
Perhaps it affords us some extra (or different) mental space in an intangible
way.

------
lutusp
Some obvious responses occur to a skeptical reader of science:

1\. This study has precisely no meaning until it has been replicated,
preferably with a larger set of experimental subjects.

2\. Science is not one study making ten claims, it is ten studies making one
claim. This study falls into the former category.

3\. The study describes, it doesn't try to explain. Science requires a
testable explanation, one that can be generalized and potentially falsified by
independent laboratories. If the study had offered a possible, testable
explanation, it would have crossed the threshold of science.

4\. It's important to say that psychological studies are virtually never
replicated. One reason is that the original studies tend to maker nebulous
claims that are difficult to quantify (like this study does). Another is that
psychological studies tend not to be accompanied by the original study data,
to a greater extent than studies in scientific disciplines. A third reason is
that psychological journals tend to reject replication papers, especially
those that don't confirm the original study's findings.

~~~
redcircle
1\. It has lots of meaning before replication, which is why people tend to
replicate things --- they were inspired.

2\. Apparently the first study isn't science. I didn't realize that science
was a catch-22 situation.

3\. This is so absurd that I feel like I'm being trolled. They have a testable
hypothesis: that acetaminophen/paracetamol has a side effect of X.

4\. See <https://yourlogicalfallacyis.com/>

~~~
lutusp
> 1\. It has lots of meaning before replication ...

Nothing in science has meaning before replication. Look at cold fusion for a
classic example where this rule was ignored. Of course, you may be speaking of
the prevailing standards in psychology, in which case you're right -- but then
psychology isn't a science.

> 2\. Apparently the first study isn't science.

That's correct -- it isn't.

> I didn't realize that science was a catch-22 situation.

Only if you can't replicate any studies. That's psychology's problem, but not
science's problem. In science, studies are replicated regularly, and no one
takes a study seriously if it hasn't been replicated, especially where human
health is concerned.

> They have a testable hypothesis: that acetaminophen/paracetamol has a side
> effect of X.

That is not an explanation, it's a description. Science requires testable
explanations. The paper doesn't presume to explain its results.

If I say "the night sky is full of little points of light", that's certainly
testable -- someone else can go outside the tent and confirm it, but it's just
a _description_ \-- not a basis for science, which requires that someone have
the nerve to suggest an explanation for what has been described.

But if I say "those points of light are actually thermonuclear furnaces like
our sun, at greater distances", I have offered a testable, falsifiable
_explanation_. That's science.

If someone correlated a specific biochemical action in individual neurons with
later very specific behavior, that might count as science, but that would be
neuroscience, not psychology. Psychology doesn't try to analytically connect
specific physical causes to effects -- it's satisfied to describe outcomes
without pretending to know _why_ they are so.

> See <https://yourlogicalfallacyis.com/>

The fallacy is yours, not mine. You appear to think one study making ten
claims constitutes science. In fact, science is ten studies making one claim.

~~~
redcircle
Perhaps you really believe this definition of science. I've never encountered
it before, nor do I know anyone that would use this definition. When people
operating on a different definition of science encounter your definition, you
can hopefully understand that they will be insulted to have what they think is
science to be called not science. Whether you meant it or not, it appears as
an attempt to elevate yourself (the person passing judgement, by calling it
not science) over the study authors. Thus it comes across as contemptuous, and
so one starts wondering: why is this person trying to belittle the study? Is
there a hidden agenda? Is this person trying to make it look like the
scientists performing the study aren't scientists, so that everyone dismisses
the results? These are the things that one will naturally wonder about in the
context of contempt, even if the contempt is accidental.

> In fact, science is ten studies making one claim.

If it is a fact, can you provide a source for this definition? I've never
heard it before, and it contradicts everything that I've encountered to date.

~~~
_delirium
From previous experience discussing on HN, I would say 'lutusp has a very
specific view of the philosophy of science, and doesn't consider it open to
debate.

~~~
lutusp
> I would say 'lutusp has a very specific view of the philosophy of science,
> and doesn't consider it open to debate.

And your evidence is that we're having this debate?

------
Breakthrough
Always great to see studies looking at the mental implications of non-
psychoactive drugs. I suppose it's common to overlook the implications of a
drug on the central nervous system with respect to consciousness, when the
drug in question never causes any subjective/noticeable change.

I suppose it's all too intuitive, though. Even slight, unnoticeable changes in
consciousness - to the point that even you don't notice - may in-fact be
detectable on paper. I hope this leads to more research into the mental
changes for other drugs classified as "non-psychoactive" (who doesn't love
more data? :). Anyways, to end off by inserting some colloquialism into my
thoughts here...

Trippy study, mannnnn.

~~~
npsimons
As someone with a family history of mental illness, I try to keep a close eye
on my mental state, and it's surprising how much can affect it. Apart from
drugs that shouldn't be affecting mental states, even different types of food
and how much exercise I get can have noticeable impacts. Those EFA fish oil
pills? Not just good for your heart . . .

~~~
freshfruit
I think you're promoting a healthy degree of self-awareness.

A noteworthy risk however is that you'll make false connections -- ie. garlic
is good for fight off HIV.

~~~
npsimons
I try to be aware of biases, but the OTC EFAs were prescribed by my physician,
and there have been some studies backing DHA in particular as effective for
depression.

------
joosters
Possibly a dumb question, by why is it called acetaminophen in some places and
paracetamol in others? Neither of them are a brand name AFAIK.

~~~
Rinum
Its chemical name is para-acetylaminophenol. That's what the names
acetaminophen and paracetamol are derived from.

para-ACETylAMINOPHENol

PARa-ACETylAMinophenOL

~~~
spicyj
para-aceTYLaminophENOL

------
coolestuk
Never mind what it is doing for your mind, in my experience, paracetamol
causes pain.

I've suffered from what doctors call "pain syndrome" for years. Many different
parts of my body are painful at any one time. It is years since I had a pain-
free day.

I never accepted that I had pain syndrome, even when doped up simultaneously
on codeine, paracetamol, tramadol and diclofenac. And still in pain. Finally I
was moved onto morphine, but I still cannot sleep at night because of the
pain.

However, I think that my pain problems were exacerbated by (at the very least)
paracetamol (max dose daily for 2 years). It is well known that sulphur
compounds (NAC specifically) are required for the detoxification of the
byproducts of paracetamol. Long term use of paracetamol will lead to sulphur
depletion in many people. And it seems this depleted sulphur is compensated by
the body taking sulphur from other places (joints, cartilage), thus causing
further pains.

Trying to get an answer from doctors and pharamacists about why taking sulphur
reduces my pain more than the above concoctions of "pain-killers" got me
nowhere, so the above is my explanation for why the more paracetamol I took
the worse my pain problems got.

~~~
Daniel_Newby
You should try drugs for neuropathic pain if you have not already:
amitriptyline, gabapentin, duloxetine, and many others.

~~~
coolestuk
Thanks for the suggestion. Tried them all. Amitryptyline made me suicidal
(turns out that is a very common side-effect, and really unwelcome for someone
who is in extreme pain). Gabapentin (and pre-gabalin) had no effect, but at
least did not cause mental disturbance the way that Amitryptyline and
Duloxetine did. The last one they tried me on was Venlaflaxine - I didn't
notice any pain reduction, but I just got insomnia from it.

It's been a bad 5 to 10 years. My opinion is that "pain syndrome" was almost
certainly not my problem. My pains were all skeletal/joint pains, except for
pains that would suddenly appear in my left hand or right calf, even when
doing nothing. Those latter two I could explain as being neuropathic, but
after being in so much pain from my back, coccyx, hips and shoulder, I think
my pain registration system was out of whack. And I wouldn't be surprised to
discover that all the different "pain killers" I was taking were in fact
contributing to further problems.

Currently I am just on morphine, but must tie myself to the bed at night to
stop myself turning over in my sleep. If I lie on my sides, the pain will
build (even through morphine) until it wakes me up. By that stage turning on
my back will not reduce the pain and I cannot get back to sleep. Taking a
sulphur supplement (NAC, or MSM) seems to be as effective as morphine (neither
alone or together is really satisfactory though).

What has been so appalling in my case, has been the difficult of getting
doctors to look at the individual problems properly in early stages (so a
dearth of scans/treatments), until it got to the point where they were saying
"you have pain syndrome". Most of the treatments that have had any success are
those that I have insisted they do even when they have said they won't work.
Some major treatments I have had to insist they don't do (cutting nerves??).

I'm finally getting a scan this week on my hips, after asking for this for
almost 2 years. Hopefully it will show what I expect it to show, and they can
treat it with steroids.

------
pygy_
Among other things, paracetamol activates the cannabis receptors.

<http://www.ncbi.nlm.nih.gov/pubmed/17227290>

------
stcredzero
_> They either watched The Simpsons or a film by surrealistic neonoir
writer/director David Lynch, in which humans with rabbit heads wander an urban
apartment muttering non sequiturs. They then passed judgement on people
arrested in a hockey riot. Again, the people in the existential mindset
imposed harsh sanctions, but the people who'd watched The Simpsons were
lenient._

I shoulda stuck with psychology after all! This sounds fun! Who thinks of this
stuff?

~~~
freyrs3
> in which humans with rabbit heads wander an urban apartment muttering non
> sequiturs

I don't know how you could sit through this film without already being
disturbed.

[1] <https://www.youtube.com/watch?v=5jSBVo59j9U>

------
guylhem
I see many post mentionning how Tylenol can be lethal in overdose due to liver
damage.

Some studies have demonstrated liver enzymes raise significantly on a typical
extra-strength dose of acetaminophen, called paracetamol in Europe. This could
be indicative of low-level damage, for casual users (it's frequently
prescribed for minor pain)

A quick and simple hack is to take it along with N-acetylcysteine, usually
given for coughing.

Personally, to play it safe, when I have to take more than half a gram of
paracetamol, or when I have to take it for more than 2 days in a row, I add
n-acetylcysteine with it.

Cheap, and without side effets at low doses. (BTW, it's used IV in the ER as
the antidote for tylenol overdosing)

~~~
gmac
I'm sure I remember a debate being had in the news at some point about whether
this antidote should be included in all paracetamol/acetaminophen pills sold.

Since this seems not to have happened, does anyone know if there's some side-
effect of taking N-acetylcysteine alongside paracetamol/acetaminophen as
standard? Or was it just a question of price?

------
noonespecial
It should at least be noted that an awful lot of those overdoses are because
narcotic painkillers are often doped with paracetamol in a misguided attempt
to keep people from using them to get high.

------
Shenglong
I'm not all that familiar with social tests like this. Is n=120 generally
considered to be a large enough sample size to make any claims at all?

~~~
carbocation
It always depends on the effect size.

~~~
icegreentea
Another important question is always, 'if this effect is true does this
generalize to the overall population'. While I haven't read the paper, I bet
that the test population were composed almost completely of undergrad
students. So much of social science experiments are based on testing done on
student. And there isn't anything wrong with that per se, but we must always
be careful when trying to infer results, and drawing conclusions on the
greater population, or human kind as a whole.

~~~
carbocation
External validity is an interesting but quite different question. There are
any number of other interesting but distinct features of clinical trials that
we could talk about.

------
gte910h
EXTREMELY small study. Just push for a larger study on this

[http://www.academia.edu/2057894/The_common_pain_of_surrealis...](http://www.academia.edu/2057894/The_common_pain_of_surrealism_and_death_Acetaminophen_reduces_compensatory_affirmation_following_meaning_threats)

121 people

Search for "We recruited"

~~~
simonster
In Study 2 there we 236 subjects, which AFAIK is a pretty big sample size for
these kinds of experiments. There error bars on the graph are still somewhat
large, so there was a lot of variability, but assuming there is no bias in
what data the experimenters chose to include, combining both studies, p <
.02*.01 = .002. Furthermore, as the article notes, there was a prior study
that also showed cognitive effects of Tylenol. While these effects could be
spurious due to publication or selection bias or deliberate manipulation, it's
not all that plausible that they happened by chance.

~~~
carbocation
Just multiplying the P-values from different studies is invalid.

You can intuit this by imagining 10000 studies, each of which had a P-value of
0.99. Seeing 10000 negative studies and no positive studies, you'd be
convinced that there was no real effect, intuitively. But multiplying 0.99
10000 times yields a P-value of 2.2 x 10^(-44), a result of impressive
significance.

To combine studies, many people use _inverse variance weighted meta-analysis_
, e.g., <https://en.wikipedia.org/wiki/Inverse-variance_weighting>

~~~
simonster
You're right. There is a mathematical explanation for this in addition to the
intuitive one you provide: If the null hypothesis is true, the p-value of each
test is uniformly distributed between 0 and 1, but the product of p-values
will not be uniformly distributed between 0 and 1, so it is not a p-value.

To combine p-values, what we really want is the CDF of the product of p1 and
p2 in the distribution formed by the product of uniform random variables.
Mathematica can compute this; the general formula is (p1p2)(1-log(p1p2)), and
for the two p-values in question this yields p = 0.0019 (which is close to
what I said initially, but only because I made a calculation error; .02*.01 =
0.0002). Thanks for pointing out the mistake in my reasoning! I learned
something.

------
powertower
> The way people pass moral judgements is not necessarily indicative of their
> level of existential anxiety.

That actually makes quite a bit of sense...

These days everyone has an opinion on everything, combined with a very
judgmental tone - and at the same time living extremely purposeless and
egocentric lifes.

~~~
Evbn
And purpose-driven zealots are not judgmental?

------
zachdonovan
Well, I for one will be taking two tylenol daily starting to day. You know, to
dull the existential angst.

------
elchief
Why do people take Tylenol, when aspirin/asa is safer and likely even good for
you?

~~~
DanBC
Aspirin is not safer. Aspirin is not "good for you" apart from narrow groups
of people taking very small doses of aspirin.

Aspirin can be harmful to the stomach lining; aspirin can be fatal to people
under 12; aspirin has a number of risky side effects; aspirin can be very
dangerous for some people with under-lying conditions.

~~~
parasubvert
Thats fear mongering. Aspirin one of the safest drugs known to man, has a much
longer history than Tylenol, and some scientists promote a more aggressive use
of it in the populace.

[http://www.nytimes.com/2012/12/12/opinion/the-2000-year-
old-...](http://www.nytimes.com/2012/12/12/opinion/the-2000-year-old-wonder-
drug.html)

~~~
shaggyfrog
Aspirin (and ibuprofen) is counter-indicated for people with stomach problems
like GERD. That's not fear mongering.

~~~
parasubvert
Of course not, but it's a big difference to say counter-indicated for one
issue vs, leading off a post with "It is not safer".

The point of this story is whether Tylenol IS safer, and that's mostly
contingent on the person (and studies showing its own inherent risks).

~~~
DanBC
Paracetamol _is_ safer. You've failed to provide any sources saying otherwise.

~~~
parasubvert
Yes, I did, if you look above, which references several studies. You on the
other hand have cited none.

------
tosseraccount
Just legalize opiods. Do you really need a Doctor when you stub your toe?

~~~
carbocation
If you take opioids for the pain from stubbing your toe, you should re-
evaluate what is important to you.

~~~
tosseraccount
Like getting by for 24 hours until I can put shoes on? I need the government
to tell me I can't ease things for a day?

~~~
Camillo
Clearly you do.

~~~
tosseraccount
In Soviet Obamerica, authority question YOU !!

