
Caffeine dosing strategies to optimize alertness during sleep loss - nickcw
https://onlinelibrary.wiley.com/doi/epdf/10.1111/jsr.12711
======
eigenspace
To everyone thinking about using caffine or other drugs to combat sleep: all
of the latest sleep reseach would suggest that 'optimizing alertness during
sleep loss' is a fool's errand if what you want is productivity. The real goal
must be to ensure you get enough sleep, not that you medicate yourself with
caffine to stop your body from getting sleep signals.

Think about it this way: If prolonged sleep were not absolutely essential to
your survival and health, sleep would be the biggest mistake evolution has
ever made. an animal spending 1/3 of its life unaware of it's surroundings is
an incredibly steep evolutionary price to pay. It should be obvious that if we
evolved to do that, there would be gigantic benefits to it, considering htat
there is not a single known animal with a nervous system that does not sleep
(including insects!). If caffine was actually helpful at reducing your need to
sleep, an animal would have evolved by now to endogenously produce caffine.

There is a substantial body of sleep literature now showing huge benefits to
physical / mental performance, willpower and creativity from sleep. Don't
fight it, use it.

_____________________________________________

Edit:

One statistic thats particularily compelling to me: Every year during daylight
savings when everyone loses an hour of sleep, the rate of heart attacks rises
by 25%. On the day of the year where everyone gains an hour of sleep, heart
attacks fall by 21%. Thats the effect of gaining / losing a single hour of
sleep.

~~~
merinowool
This is a sound advice. I spent 10 years of my life trying to squeeze as much
time awake time as I can using tons of coffee and that almost ruined my life
and got me nowhere. I have managed to get some success in life once I gave up
on that idea and was productive when I was feeling productive without forcing
it. If I can't do anything during the day? Fine. If I feel sleepy? I go to
sleep. It was important though, to wake up at the same time in the morning. I
was unable to kick off the coffee addiction, but reduced it just one cup in
the morning. I find coffee more difficult to quit than cigarettes.

~~~
malnourish
I quit tobacco about 4 years ago after using for 7 years. I agree that
quitting caffeine is more difficult, but I think part of that is social. I can
enjoy sharing a cup of coffee with my SO just about anywhere without any dirty
looks.

~~~
samsonradu
Oh yes, coffee is one of the less harmful pleasures of life! I would never
consider quitting it, that doesn’t mean I’d neglect sleep though.

------
jillesvangurp
Club mate is the drink of choice in the start up community in Berlin. I've
made the mistake of drinking that in the evening a couple of times and
regretted that at 4am by being wide awake and unproductive the next day. If
you are not familiar, mate tea which this is based on contains a form of
caffeine that is particularly potent. It's like drinking multiple espresso
shots. Don't drink this if you have blood pressure issues.

In general, I've learned to moderate my caffeine intake and restrict myself to
mornings only. The more you consume, the more you need of it to work at all,
and the more likely you are to have side effects like feeling tired, having
poor sleep rythm, headaches, etc.

When used in moderation it's a great tool for getting yourself productive
after a lazy weekend on a monday morning. However, if you feel tired all the
time, stop drinking coffee and get a few nights of good sleep in.

~~~
crazygringo
> _" a form of caffeine that is particularly potent"_

I've heard this over and over, but as far as I can tell, caffeine = caffeine =
caffeine. I'm not a chemist, but I can't find any mention of any different
forms -- it's C8H10N4O2. [1]

Is there any scientific evidence that alertness is related to anything but the
quantity of caffeine, regardless of whether it's delivered as black tea, mate
tea, coffee, pills, etc.? Assuming that the caffeine makes it into the
bloodstream at the same rate?

[1]
[https://en.wikipedia.org/wiki/Caffeine](https://en.wikipedia.org/wiki/Caffeine)

~~~
yomly
Caffeine == Caffeine

But if a Coke is ~3mg caffeine 100ml and coffee is ~40mg per 100ml, drinking
13.3 "units" of cokes will not be equivalent to 1 "unit" of coffee.

1\. Timing of the intake will affect the efficacy (x mg of caffeine over 2
hours vs. 20 minutes is very different to the body)

2\. Controlling for time-dependent intake (the spherical human consumed both
quantities instantly), concentration of the substance affects the rate /
efficiency of absorption by the body (I cannot predict for which way it will
go, this stuff is complex) so the net absorbed caffeine will be different
between the two substances

3\. Delivery mechanisms are different: Coke is very sugary, black coffee is
not and is a colloidal suspension. The local chemical environment for the
caffeine within these two substances will be different. Sugar is known to
affect osmosis, meanwhile who knows wtf the gunk in coffee is doing at the
chemical level.

So to sum up "caffeine = caffeine = caffeine" is probably a useful rule of
thumb and will get pretty far, but at the physiological/biochemical level,
that is as useful as armchair pseudoscience is.

To use a possibly relatable issue: most people find consuming shots of vodka
more efficacious than consuming the equivalent amount of beer by alcohol. 3
shots will probably get you more wasted than necking 3 beers

~~~
dtech
> To use a possibly relatable issue: most people find consuming shots of vodka
> more efficacious than consuming the equivalent amount of beer by alcohol. 3
> shots will probably get you more wasted than necking 3 beers

But it won't, after drinking 3 beers after each other your BAC will go to the
same level, just takes a little more time to get there.

Subjectively, you start feeling drunk much more quickly because the change is
faster with Vodka, but your capabilities are as much impaired.

~~~
kryogen1c
This is not true and is the nature of the discussion. Alcohol and caffeine are
processed differently depending on what they are consumed with, like how the
digestive cofactors in apples make it have a lower glycemic index than it's
fructose content should produce. To stay with alcohol, this is easily
testable. Drink five shots of vodka and see how drunk it gets you. Separately,
drink five shots of vodka with honey added and you will get significantly
drunker. Your liver prioritizes sugars first, so the alcohol is rapidly
absorbed and takes effect instead of being processed out. You do not reach the
same BAC in each case, just like drinking 5 shots in five days won't either.

------
walkingolof
Caffeine is also linked to panic attacks, anxiety and sleep loss (and loss of
quality of sleep), I would recommend staying off caffeine all together, having
tried both, I by far more like working in the calmness of not having caffeine
circulating in my body.

[https://en.wikipedia.org/wiki/Caffeine-
induced_anxiety_disor...](https://en.wikipedia.org/wiki/Caffeine-
induced_anxiety_disorder)

~~~
skipants
Counter-point: I once quit coffee altogether, weening myself off with tea at
first. After about 3 months of total caffeine "sobriety" I hated it. I found I
enjoyed myself more and was more productive with some caffeine rather than
none. It did help me cut back (I went from ~8 cups a day to ~2-4).

I think the level I'm at now -- still ~2-4 cups -- is perfect. I find I'm
productive and still sleep well.

Note: 2-4 cups still sounds like a lot, but I mean 1 cup = 250ml not 1 mug.

~~~
frfl
8 cups?! You should drink that much water - but coffee..

2-4 still seems like a lot - this is coming from someone who doesn't drink at
all anymore, but before 1, maybe 2. Now I only drink if I know I need the
alertness. More effective for me considering the caffeine tolerance is gone
and even a little has full effect.

Why did you hate it?

~~~
skipants
It's pretty easy to hit 4 cups. Large cups of coffee are 20 fl oz which are
~570ml. So 2 larges in one day, which I have from time to time, will get you
there.

I can't really explain why I hated it with complete accuracy -- I think I just
felt overall less energetic. And I felt this way when I was definitely over
the effects of caffeine withdrawal.

------
nottorp
How about, you know, sleeping? Working in a startup isn't being parachuted
behind the enemy lines where your life depends on staying alert. Go home,
you'll work better tomorrow.

~~~
protonimitate
I have mild ADD and tons of issues with migraines. Caffeine helps on both
fronts.

Do what's best for you, personally, and not what some internet stranger thinks
is the correct way to function.

~~~
eigenspace
I know nothing about your medical issues, but to bring up a counter-point,
it's possible that your 'mild ADD' and migraines are the symptoms of
insufficient sleep quantity of quality. Medicating with caffeine could be
counterproductive if that's the case.

~~~
protonimitate
Fair point, but I get 8 hours of solid sleep a night and can drink caffeine up
until I go to bed and it won't keep me awake.

I've also done sleep studies and endless 'preventative' medicines for
migraines but nothing has worked so far.

Caffeine is definitely not a cure-all, and I don't want to argue that it's
good to use, but it's also not fair to blanket statement and say that everyone
should avoid it at all costs :)

~~~
sp3000
[https://www.psychologytoday.com/intl/blog/sleep-
newzzz/20131...](https://www.psychologytoday.com/intl/blog/sleep-
newzzz/201312/new-details-caffeine-s-sleep-disrupting-effects)

Caffeine disrupts the quality of sleep even if you are not aware and feel like
you are sleeping fine. I'm not saying this is the cause of any issues you
have, but just want that to be considered.

Attention and focus have strong correlations with sleep quality. I say this as
a fellow "ADD-er", and only point this out because, being in the health field,
I see so many people who completely neglect proper sleep hygiene and then
wonder why they feel like crap all the time. This makes me suspect that most
of the population has no clue how important proper sleep is to quality of
life.

------
dec0dedab0de
Anecdotally, water and sugar directly affect my alertness while using
caffeine. If I don't have enough water I get headaches and can't think
straight. If my blood sugar is low due to not eating enough, or eating too
much sugar and "crashing" then I might as well be asleep, even though I can't
from the caffeine.

I may have missed it, but I don't see where they account for the diet of their
test subjects.

~~~
marpstar
another anecdotal story: I generally skip breakfast and lunch and do most of
my eating after work. I find that the longer I fast the more I can focus,
provided that I stay hydrated. I do use caffeine (almost exclusively black
coffee) for alertness and appetite suppression.

~~~
julian37
IANAD (not a doctor) but just as a note of caution, I remember reading that
eating one large meal a day rather than several smaller ones can have adverse
consequences due to stress on the oesophageal sphincter. This study appears to
come to that conclusion:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223119/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223119/)

(I'm not judging, I've been known to skip the odd meal here and there myself.)

~~~
marpstar
Interesting study. I do suffer GERD symptoms, but fasting hasn't seemed to
have an effect on the severity of symptoms, though

I do notice particular things CAN give me GERD more _often_ , particularly if
I eat something high in sugar on an empty stomach, especially if I've had a
lot of coffee that day. I need to have "real food" in my stomach before I can
do candy, donuts, etc.

This is the primary reason I started skipping breakfast. I know, I
know...donuts aren't an ideal breakfast, but they're hard to resist when
someone brings them in the office and you don't remind yourself that you're
going to suffer from heartburn all morning if you indulge.

------
4ad
I drink a lot of tea. About 1 liter a day as a baseline, but if I do some
ultrahike or something I can easily drink 3 liters a day. Sometimes for some
reason it's really hard to drink my tea (e.g. I'm in a hotel that doesn't have
drinkable tea), so I tried to substitute with other caffeine products.
Unfortunately I couldn't find out any reliable data on the caffeine content of
the tea that I drink. All the information I could find is the worthless X-5X
mg caffeine/cup, usually without even defining what a cup is!

Does anyone know a better resource?

Anyway, subjectively speaking I find that all the online estimates are too
low, at least for the type of tea that I drink and in the concentration I
prefer.

Also, subjectively it seems that tea has a more complex psychoactive effect
that either pure caffeine or coffee. If I drink enough caffeine, I can avoid
the symptoms associated with caffeine withdrawal, but I don't get nowhere near
as strong as an effect as I get from from tea, even if I drink a lot of
caffeine. It appears tea has other stuff in it apart from caffeine.

Now when I travel I take my own tea, cup, and immersion heater with me.

As I said, I really like tea, but only good tea that properly prepared is
good. What passes for tea these days, sometimes even in tea shops (!) is
usually poison. An easy litmus test is this: do they use a thermometer when
making green or white ea? If not, that means they use boiling water which will
destroy the tea. I think most people never had good tea in their life. I
strongly dislike coffee, but I somehow suspect I only drank bad coffee that
was not prepared correctly, and that I would enjoy good coffee.

~~~
Legogris
High- and medium grade green tea (especially the Japanese varieties) have
significant amounts of L-theanine, which has its own effects and synergies
with caffeine. For me, the same amount of caffeine will have me anxious and
give me tunnel-vision if I get it from coffee while more euphoric and peppy if
from green tea.

~~~
mkirklions
What should we be feeling with L-theanine?

I never found it affected me.

~~~
skore
With good green tea that has lots of it (shaded tea, but doesn't need to be
gyokuro, Sencha Momiji is my favorite, cold brewed over night, then strained
in a french press), I usually feel a slow but steady rise in wakefulness and
around the time where I would start to get jittery (say, like when drinking a
few too many cokes), it transitions over to an incredible calm mixed with a
feeling of... wideness. Like your FOV is actually expanded by a few degrees,
on many levels. Close your eyes and it feels like being at peace in a kind of
Zen state. But... with a little buzz, very much an eager, productive peace
where things line up and you can approach them.

It's probably different for different people, but I can highly recommend
trying to "get some good stuff" to see whether it can do the same for you. I
wouldn't want to miss it.

~~~
Legogris
This!

Another curious thing I have noted: While living in Japan I was binging on
houjicha[0] (which has significantly less caffeine due to the roasting
process) on late evenings so I would still be able to sleep. After several
strong pots (we are talking litres of 1:1 water/leaf ration) I would often get
into a different mind-space that is pretty close to what you are talking
about. I tried to research if other catechins (like l-theanine) also disappear
in the roasting process or if they could be the explanation, but weren't able
to find anything to back this up.

0:
[https://en.wikipedia.org/wiki/H%C5%8Djicha](https://en.wikipedia.org/wiki/H%C5%8Djicha)

------
growlist
Personal anecdata, I was drinking several cups of coffee to get myself through
7 hours' driving with a full work day spliced within. I used to feel
absolutely dreadful. Why am I so tired despite drinking all this coffee? I
used to think. I then started limiting myself to one small coffee a day.
Bingo, all symptoms gone. The coffee was making me feel far worse than I would
otherwise have done as it wore off, I believe.

~~~
WhompingWindows
It's alertness effects go away after repeated use and subsequent tolerance
building. The best way to use it is in moderation: decaf or no caffeine some
days, caffeine other days when it is needed. Drinking it daily is common and
often done out of liking/habit/addiction or some combination of those.
However, the best positive effects will be seen with moderation.

~~~
eggsyntax
"It's alertness effects go away after repeated use and subsequent tolerance
building"

Link to evidence? I don't remember seeing anywhere in the literature that
caffeine stops being effective when used daily and long-term, nor does it
match my own experience.

Thanks!

------
_ak
Interesting detail: look at where they authors are working. This is military
research. And I'm not surprised. The problem of having to keep soldiers alert
during long phases of sleep deprivation has been around since the early days
of modern warfare.

~~~
mkirklions
Yes, this didnt seem like it was useful for daily use.

48 hours without sleep isnt realistic for most cases, and I dont think these
results have anything to say about daily caffeine.

Also, I think the best advice is to learn your body. I cycle caffeine every
few months. 2 cups all at once before I need 5 hours of productivity.

~~~
jadedhacker
Yea, I think the 48 hr sleep deprivation is not applicable to most people. The
task also is a kind of "vigilance" task. I don't know if it applies to any
kind of productive thinking. They also studied chronic sleep deprivation,
maybe that would be helpful for people.

------
acconrad
In case anyone found that study difficult to read, the optimal strategy was,
over the course of 3 days, one 600mg dose after 12pm on days 2 and 3 of a 3
day string of sleep loss.

~~~
themodelplumber
Thank you. I was thrown off because I couldn't believe I was looking at
post-12pm. Those are pretty extreme circumstances.

In my own case I've been tracking caffeine use and some helpful strategies
are:

\- 30mg after a brief afternoon nap

\- 50mg to 60mg after a long afternoon nap that resulted in grogginess

\- 100mg after a terrible night's sleep and before a long meeting

\- Extreme care if I have an exhaustion headache due to lack of sleep and
overproduction; caffeine often triggers migraine here

~~~
monktastic1
12 pm is noon not midnight, in case that's what threw you off.

~~~
themodelplumber
Of course it would. :-) Thanks! 600mg still seems crazy strong but I guess
everybody's different.

~~~
monktastic1
Yeah, I feel like I'd have a heart attack well before that myself.

------
trendia
Genetics play an important factor. CYP1A2, one of the enzymes that metabolizes
caffeine, varies by as much as 40x between individuals.

In those with a high level of the enzyme, caffeine is metabolized quickly, so
they can drink coffee in the afternoon and still fall asleep. They are less
likely to get anxiety from caffeine, and do not suffer from a higher risk of
heart attacks with coffee consumption.

In contrast, a small amount of CYPA12 prevents caffeine from being metabolized
and prolongs its effects.

[0]
[https://en.wikipedia.org/wiki/CYP1A2](https://en.wikipedia.org/wiki/CYP1A2)

~~~
simonebrunozzi
My dad (in Italy) drinks his last espresso after dinner, at ~9pm, every night,
and soundly falls asleep by 10:30am.

Perhaps he has a high level of CYP1A2? I am wondering if there's a cheap but
effective method of measuring it.

~~~
leshow
I realise you said 'perhaps' but I have to comment on how much I dislike this
kind of backwards reasoning. I used to compete in bodybuilding, and I heard
arguments like this all the time. "I'm not making progress, I must have low
testosterone", "I must not be metabolizing protein", etc. The number of
possibilities is huge, you really can't say with any certainty what the cause
is.

Most likely he just has a tolerance to caffeine from drinking it. It sounds
like he drinks it all day.

------
baldfat
Trick: Boost your adrenaline by doing exercise before drinking down the
caffeine.

I learned that caffeine makes adrenaline last longer by blocking it receptors
in college.
[https://science.howstuffworks.com/caffeine4.htm](https://science.howstuffworks.com/caffeine4.htm)

My trick is no adrenaline no caffeine effect. I would do 10 push ups or run
around my car a few times and then drink down the caffeine and that changed
everything.

~~~
hawkice
Isn't the half-life of adrenaline like 90 seconds? Wouldn't you be a nervous
wreck if it lasted much longer?

~~~
Jaruzel
I think the parent comment is talking about the _effects_ of adrenaline not
the adrenaline dump itself.

As someone who, prior to being medicated, used to get a lot of panic attacks,
I can safely say that the effects of too much adrenaline being dumped all at
once is pretty inhibiting.

------
baxtr
_> Caffeine, if safely administrated, is an effective countermeasure to
mitigate impairment of alertness caused by sleep loss. This has been
demonstrated in multiple laboratory and field studies for different sleep–wake
schedules. However, to maximize its effectiveness, caffeine should be consumed
at the right time and amount. Here, we developed an optimization algorithm to
determine when and how much caffeine to consume so as to safely maximize
alertness of a group of individuals for any situation_

I couldn’t find the algorithm though...

~~~
e407
They built their own tabu search algorithm (section 2.3)

~~~
amelius
How large is the search space?

------
davidjhall
there's an app, caffeine zone, that helps you find out the right time. I don't
know if it based (or been updated based ) on this study.
[http://frankritter.com/caffeinezone/](http://frankritter.com/caffeinezone/)

------
drunkenmeister
Is there a way we can use this algorithm for personal use?

~~~
mkirklions
Do you stay up for 48 hours straight?

Probably not.

I think the best advice is to learn your own body. Sure there are similarities
between everyone, but good caffeine habits are more important than the dosage.

------
amelius
What are the inputs of the algorithm?

I couldn't find it after reading the abstract and quickly scanning the first
page.

------
no_identd
[https://2b-alert-web.bhsai.org/](https://2b-alert-web.bhsai.org/) \-
Implementation of previous research on this by the same people, who currently
work on adding this improved model to the implementation.

------
ulisesrmzroche
I drink about a gallon of caffeinated drinks a day, sometimes more. Am I the
only one?

I don't have problems sleeping, headaches, or with fatigue. I look forward to
the jitters; it actually cheers me up to know that soon I'll be so intense.

~~~
robbiep
~ 25% Caucasians are fast metabolisers of caffeine so can expect to not notice
much of a change with standard doses. Doesn’t mean it isn’t doing it’s thing
on a biochemical level (both reuptake of intracellular adenosine and driving
tolerance)

~~~
ulisesrmzroche
I was born and raised half my life in Mexico, so I probably don’t have that
trait.

I wonder if perhaps there’s something related though.

~~~
robbiep
23 and me will tell you for $100

------
euroclydon
Surely there’s a better drug than coffee for staying awake for a long time.

~~~
_ak
The Germans used metamphetamine during World War 2. They gave it nicknames
Panzerschokolade ("tank chocolate"), Stuka-Tabletten ("Stuka tablets"),
Herman-Göring-Pillen, or Flieger-Marzipan ("pilot's marzipan"). It was freely
available under the brand name "Pervitin" until 1941. From then on, you needed
a prescription in order to purchase it.

~~~
ekianjo
The Japanese also had similar drugs in free circulation during ww2 if I
remember correctly.

~~~
nervousvarun
Not only that, the Japanese actually invented (synthesized) Meth in 1919.
source:
[https://en.wikipedia.org/wiki/Methamphetamine](https://en.wikipedia.org/wiki/Methamphetamine)

It's still one of the most popular (if not the most popular) illegal drugs in
Japan. source:
[https://en.wikipedia.org/wiki/Legal_status_of_methamphetamin...](https://en.wikipedia.org/wiki/Legal_status_of_methamphetamine)

------
ddtaylor
My goal has been to increase protein intake and reduce my caffeine. My body
and brain works better when fueled with protein. With caffeine I have to
"refuel" every 30 - 60 minutes and snack on stuff but with a big protein meal
I find myself not thinking of food or drink for 3 hours of hard focus.

------
pier25
Off topic, but...

Anyone knows what PDF renderer Wiley is using? The performance is fantastic.

Is this PDF.js?

Edit: Found it [https://www.readcube.com/](https://www.readcube.com/)

Edit 2: Apparently ReadCube uses PDF.js

------
maxk42
It should be noted that all they've done here is create a computer simulation
with no controlled in vitro measurements of performance.

This does not necessarily predict real-world effects.

------
intrasight
I've learned, after too many years - no caffeine after 10am

------
collyw
Anecdotal I know but since trying to eliminate refined sugar from my diet I
can manage the occasional night or two without sleep pretty well, no caffeine
required.

------
perlpimp
caffeine + l-theanine + picamillon. get you going steady. awake or asleep.
Sleeping though is in no way replaceable. 8-9 hrs 10-6. Even fact this is
mentioned here, is a bit insulting. There should be a study of how many bugs
that you produce when awake but sleep deprived with/without caffeine vs well
rested( no caffeine after 1pm, no food after 6pm)

~~~
mkirklions
>picamillon

Not legal in the US... :(

------
cm2012
A bit off topic, but if you like good coffee, /r/coffee is a great online
community.

~~~
avcdsuia
And if you only like drugs, /r/nootropics is a great place to discuss
seriously.

------
sAbakumoff
Is there the TLDR version of this paper?

~~~
Bakary
The summary on the first page?

~~~
albertgoeswoof
I think he/she is asking for a more actionable summary. E.g. consume 10mg of
caffeine every 4 hours from 6am till 2pm etc.

~~~
dosy
After 10 minute read here's what I get out of it:

The study is a meta study that doesn't actually test individuals but uses data
from other studies that do test individuals to assess average group
performance under sleep deprivation (either total or chronic restriction)
using an algorithm that tries to use the other studies as inputs and predict
their results to draw out patterns by finding dosing strategies that optimize
performance.

The advice seems to be: reduce total caffeine amount because otherwise
recovery to normal is worse, take more caffeine on days with less sleep, and
less on days with more sleep, delay the dose to closer to sleep period (
otherwise your performance tanks as your approach sleep period, i.e., you only
stay high for so long ), and if you can don't dose on the first and last days
of your sleep restriction period, just go "natural".

------
anoncoward111
Honestly guys, my opinion in this day and age is that pretty much any
substance you put into your body (including water and air) can be toxic.

Some are more vital than others. We have a pretty clear need for lots of air,
and a fair amount of water.

But it isn't as reasonable to think that our evolution intended or makes
accomodations for caffeine intake.

Ingest at your own risk, whatever the dose. My wallet and my brain tell me to
just go without it in my life.

~~~
wufufufu
I agree with "But it isn't as reasonable to think that our evolution intended
or makes accomodations for caffeine intake." However, caffeine has been tested
over generations and doesn't really have any major consequences as far as I
can tell. I do think that a lifestyle where caffeine makes you more effective
is probably not optimally healthy, but since when does anyone care about that.

~~~
anoncoward111
I agree that all health decisions are a trade off between risks and benefits.

But, in sufficient dosages, caffeine can cause heart attacks, paranoia, spasms
and so on. It is a neurotoxic substance.

Of course, you need to massively overdose for these things to happen. Water
can be deadly if you overdose it as well. But perhaps we are missing minor
damage that's occurring even with proper dosages

