
Acetaminophen may hinder the brain's error-correction mechanisms - elorant
http://www.scienceagogo.com/news/20160308231517.shtml
======
facetube
Acetaminophen metabolizes to
[https://en.wikipedia.org/wiki/AM404](https://en.wikipedia.org/wiki/AM404),
which may act indirectly on endocannabinoids or CB1 receptors.

Acetaminophen has been shown to have an effect on social pain/rejection as
well:
[http://www.ncbi.nlm.nih.gov/pubmed/20548058](http://www.ncbi.nlm.nih.gov/pubmed/20548058)

It's an interesting drug.

~~~
unclebucknasty
Also appears to subtly alter our moral judgment:

[http://www.theatlantic.com/health/archive/2013/04/whats-
tyle...](http://www.theatlantic.com/health/archive/2013/04/whats-tylenol-
doing-to-our-minds/275101/)

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daveguy
It says "painkillers" \-- a very general term -- but the study was on
acetaminophen (tylenol). Obviously the results don't directly hold for
aspirin, ibuprofen, etc. Although, it would be interesting to do a similar
study of other painkillers.

~~~
sillysaurus3
What are some of the differences between the various types of painkillers?
I've never thought about it.

I'm hoping for a highly technical answer, but anything would be interesting.

~~~
daveguy
I'm not sure if you have any biomedical background so I will start from the
beginning. Looking for details on "how a medicine works" the key phrase is
"mechanism of action". This is a description of known interactions of a
medicine with protein molecules in the body. DNA is code for proteins and
proteins are the interactors in the body (a rough analogy is DNA is the source
code, proteins are the binary).

So, the mechanisms of action are the key to both major effects and side-
effects. If a medicine works well, it mediates a single pathway of protein
interactions and produces no degradation products or side-effects in other
pathways. Here are wikipedia descriptions of mechanisms of action for
different medicines:

[https://en.wikipedia.org/wiki/Paracetamol#Mechanism_of_actio...](https://en.wikipedia.org/wiki/Paracetamol#Mechanism_of_action)

[https://en.wikipedia.org/wiki/Mechanism_of_action_of_aspirin](https://en.wikipedia.org/wiki/Mechanism_of_action_of_aspirin)

[https://en.wikipedia.org/wiki/Ibuprofen#Mechanism_of_action](https://en.wikipedia.org/wiki/Ibuprofen#Mechanism_of_action)

They do have COX inhibition in common. COX is a protein enzyme that mediates
pain and inflammation response:

[https://en.wikipedia.org/wiki/Cyclooxygenase](https://en.wikipedia.org/wiki/Cyclooxygenase)

However, they have slightly different side effects (secondary interactions)
and some may have additional primary interactions (those that mediate pain).
For instance there is evidence that tylenol has direct interaction with
receptors in the spinal cord to mediate nerve signaling (separate from
inflammatory and pain response sources via COX).

So, the indication of a side-effect with acetaminophen does not imply there is
a definite side-effect with all painkillers (or even all COX inhibiting
painkillers). Although it is a good indication that other painkillers should
be evaluated for the effect and if it is common to all COX inhibiting
painkillers then it may be that specific path.

Living animals are a beautiful and complex interaction of proteins and small
molecules. It is exciting when we determine how one piece of the puzzle might
work. The complexity involved makes it difficult to broadly apply results
until the broader context has been evaluated.

~~~
sillysaurus3
This was a wonderful comment. Thanks very much!

~~~
goldenkey
Just to clarify, all over the counter painkillers are NSAIDs, non steroidal
anti inflammatory drugs. And like OC said, they all inhibit COX1 and COX2.
Selective COX1 inhibitors have been created as prescription drugs to avoid
effects of stomach ulcers and liver damage but were pulled off the market due
to studies showing increased risk of heart attacks. Ie. Celebrex

[https://en.m.wikipedia.org/wiki/Celecoxib](https://en.m.wikipedia.org/wiki/Celecoxib)

[https://en.m.wikipedia.org/wiki/NSAID](https://en.m.wikipedia.org/wiki/NSAID)

~~~
DanBC
[https://en.m.wikipedia.org/wiki/NSAID](https://en.m.wikipedia.org/wiki/NSAID)

> Paracetamol (acetaminophen) is generally not considered an NSAID because it
> has only little anti-inflammatory activity. It treats pain mainly by
> blocking COX-2 mostly in the central nervous system, but not much in the
> rest of the body.[3]

~~~
goldenkey
Personally I take Naproxen Sodium (Aleve.) It has a long half life and high
anti-inflammatory activity. One thing to note is that NSAIDs are best taken in
high doses sparingly rather than a temperate dose daily. Inflammation is best
defeated by impulse of NSAIDs. I suffer from chronic pain due to herniated
discs. When I notice it is due to inflammation I take 2 Aleve extra strength
gel caps. And the inflammation subsides for at least a week or two. I know
this isnt totally related and slightly anecdotal but as hackers I figure that
you guys would like to know from a fellow hacker that did the research.

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another-one
I have OCD (obsessive compulsive disorder). Where a normal person may have a
fleeting thought about something and discard it, my brain can get "stuck" on
that thought.

I view it as the check mechanism NOT kicking in as it should.

I have found that acetaminophen helps to put the check mechanism back in
place. It can slow down or stop the runaway train.

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dingdingdang
Some people have been saying this for a while: "The Alzheimer Pandemic: Is
Paracetamol to Blame?" \-
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/)

~~~
jey
No, that's [probably] caused by anticholinergics:
[http://www.health.harvard.edu/blog/common-anticholinergic-
dr...](http://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-
benadryl-linked-increased-dementia-risk-201501287667)

------
golemotron
It's interesting to consider what we might learn about the mind/brain by tying
this result to the one that came out a few years ago - acetaminophen reduces
'existential anxiety:

[http://www.psychologicalscience.org/index.php/news/releases/...](http://www.psychologicalscience.org/index.php/news/releases/experiencing-
existential-dread-tylenol-may-do-the-trick.html)

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nonbel
Anyone know the best way to open a ".spv" file? The data for this paper is
"free" as long as you have SPSS apparently. I was able to get the .sav file
opened, but many of the column names mean nothing to me.
[https://osf.io/xpmd2/](https://osf.io/xpmd2/)

~~~
DanBC
IBM have a free viewer.
[http://www-01.ibm.com/support/docview.wss?uid=swg21479879](http://www-01.ibm.com/support/docview.wss?uid=swg21479879)

I have no idea how useful that is.

> Question

> How does one view IBM SPSS Statistics output if s/he does not have
> Statistics, or has an earlier version than that which produced the output?

> Answer

> For output produced by versions of SPSS/Statistics 16.0 and later (i.e.,
> *.spv files), the free IBM SPSS Smartreader is available for Windows, Mac,
> and Linux from the SPSS Community
> (www.ibm.com/developerworks/spssdevcentral). Look for the Download materials
> for IBM SPSS Statistics.

~~~
nonbel
Anyway, I figured it out by comparing the means of the columns to the tables
in the paper[1]. I was wondering about the claim that "the magnitude of an
individual’s Pe correlates positively with omission errors", since they do not
show this plot.

You can see it by plotting "pe.diff.meanpz.cpz" vs "percent.omission.errors"
from the data.sav file at the OSF link (I used the R "memisc" package). There
is a correlation, but just slightly (eg the subjects with the highest error
had middling Pe).

Also, the error rates correspond to the control group _not_ clicking (on
average) when they saw an F instead of an E 1-2 times out of 60 vs 3-4 times
for the acetaminophen group.

They say "the effect of acetaminophen on errors of omission, while robust, was
unanticipated". So this was the result of exploratory analysis. Personally I
wouldn't put much stock into the idea that acetaminophen "hinders the brains
error correction mechanism" based on these results.

[1]
[http://www.ncbi.nlm.nih.gov/pubmed/26892161](http://www.ncbi.nlm.nih.gov/pubmed/26892161)

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marvel_boy
Newbie here. Not sure If I understand correctly. So, there is a reason to not
take painkillers at work?

~~~
brimstedt
Ia there a reason TO take painkillers (at work or not)?

If you are not seriously ill, like having cancer or a broken bone, why do you
take painkillers?

Imo, by taking pain killers you shut of the bodys built in protection thats
telling you either to eat, drink or rest.

Few people should require to do this.

If you require painkillers to get through the day (or year) you should
consider your position and how youre treating your self and your body.

~~~
jakobegger
I've suffered from semi-regular headaches -- sometimes every week, currently
about once a month. I don't know what's causing them; the neurologist said
it's migraine, another doctor said it might be allergies, other people told me
that they are probably related to tension in my spine and another well-meaning
friend told me I should just drink more water.

Ibuprofen lets me get rid of my headache 90% of the time.

Sure, frequent painkiller use has side effects (stomach troubles for me), but
the alternative is spending two days in pain unable to concentrate.

I know a few people who have been suffering from headaches all their life, and
there just isn't a simple lifestyle change that will get rid of it.

~~~
Flow
I have a very similar story. Have you tried any medicines against anxiety? It
could be something as simple as magnesium and water. Or Atarax or Buspirone.
I've discovered these reduce the chance of a headache breaking out by quite a
bit.

But if there's a real tension/migraine headache, ibuprofen is the only
medicine that I've tried that helps.

But these days I'm very careful about taking ibuprofen, it hurts my stomach
and I've already suffered vitamin B9/12 deficiency once. Not fun at all.

~~~
beefield
Have you tried something like
[https://en.wikipedia.org/wiki/Omeprazole](https://en.wikipedia.org/wiki/Omeprazole)
when eating ibuprofen? I am not a doctor, but I have understood that it is
recommended if you have issues with ibuprofen and stomach.

~~~
Flow
Yes I have. It works ok most of the time.

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alexandercrohde
I think this title can be misleading, be sure to read the article closely.
From the article, what when they say "error correction," all they mean
learning a new task while under the influence of aspirin is lower.

Which to me seems obvious given that it's a social-pain reliever. Frankly, a
psychology experimentee has no motivation to "score well" other than pride, so
any drug that reduces the sensation of shame would make an experimentee try
less hard.

~~~
tempestn
Just a note, acetaminophen isn't aspirin. Acetaminophen is known as
Paracetamol in some places, and is sold as Tylenol brand.

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hyperpape
Has anyone looked at the article and can comment on how large the effect is?

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readme
According to science, they may...

According to my personal experience, they definitely do.

~~~
cpncrunch
Care to explain further?

