
Nicotine Normalizes Brain Activity Deficits That Are Key to Schizophrenia - baalcat
http://neurosciencenews.com/schizophrenia-nicotine-brain-activity-5995/
======
qrybam
Tangential self experimentation anecdote:

I was intrigued by reports that nicotine can improve cognition in otherwise
healthy people so I read through as many studies/articles I could find online.
After deciding that I'd done enough research I took the plunge and began self
experimenting with 2mg gum. I took it daily throughout the day at regular-ish
intervals for around 2-3 months.

The affects I experienced were as follows:

* it had a positive impact on my focus

* it provided a boost to my wakefulness if I had a bad night's sleep

* my brain felt like it would "tighten up" while I was taking it

* my body felt like it was experiencing higher blood pressure

Short term I was happy with the results.

I am a fit and healthy, non-smoking, cognitively normal (afaik) middle aged
male.

After almost 3 months of taking nicotine gum I developed a cyst in one of my
retinas brought on by "high pressure damage to the blood vessels".

When I measured my blood pressure, my base pressure had increased by ~10% (as
compared to pre-experiment, measured over several days). The real problem
would happen if I was under stress, my BP would spike to dangerous levels when
it never had done before. I also felt that I would get stressed more easily.

My blood pressure took a few weeks to drop back to normal. I didn't have any
withdrawal symptoms save for the sensation of chewing gum.

I won't be repeating this experiment.

Sharing this story in case you're considering long term usage, whether for
medical or experimental purposes.

Medical literature seems to support this experience (although supposedly the
effect is smaller in women, sorry couldn't find the source for this particular
point):

[0]
[https://www.ncbi.nlm.nih.gov/pubmed/12356338](https://www.ncbi.nlm.nih.gov/pubmed/12356338)

edit: spelling

~~~
mona_simpson
Take-away from that is to look up the literature /before/ carrying out the
self-experimentation. It could have saved the nasty experience with the retina
cyst which sounds very nasty.

I guess we normally only get to hear of the self-experiments with great
results and advances for science and medicine. The not-so-good results can
tend to get buried both figuratively and literally.

Hope you're fully recovered.

~~~
yarou
I'm sure someone who's never exercised before could die of cardiac arrest as
soon as they step on a treadmill.

I think it's slightly disingenuous to suggest that one should never take risks
because there are possible downsides.

Nicotine exists in tomatoes, potatoes, etc. Should I remove these from my diet
because they contain nicotine, which might possibly cause a cyst in my retina?
Surely, we would both agree that argument is nonsensical.

~~~
Alex3917
> Surely, we would both agree that argument is nonsensical.

It's nonsensical because the dose of nicotine in either is basically zero,
unless you're eating pounds of raw tomato leaves.

------
lawpoop
I'm convinced that if it were suddenly discovered today, nicotine would be
hailed as a miracle drug.

It has several properties. It's both a stimulant and a relaxant. It helps you
focus without burning out your neurons and inducing psychosis like
amphetamines.

[https://en.wikipedia.org/wiki/Nicotine#Psychoactive_effects](https://en.wikipedia.org/wiki/Nicotine#Psychoactive_effects)

[https://en.wikipedia.org/wiki/Nicotine#Enhancing_performance](https://en.wikipedia.org/wiki/Nicotine#Enhancing_performance)

While there is some risk to it, the actual danger (cancer, heart attack,
stroke) from smoking is due to the tar content and other products of
combustion from burning tobacco. While nicotine doesn't help blood pressure,
it's not the killer that smoking is. It's also somewhat carcinogenic -- again,
not as much as tobacco smoke and tar itself. You can find 80 and 90 year old
smoking, but you can't really find elderly using cocaine, for example. As far
as drugs go, it's relatively safe, for the benefits that it provides.

Also, there are several MAOIs in tobacco smoke. MAOIs are used as last-line
anti-depressants, because of their side-effects when taken in large doses. But
with tobacco products, a user basically gets a tritrateable MAOI.

If we suddenly discovered nicotine today, I'm convinced that either it or a
close chemical cousin would be a the next miracle drug for anxiety and
depression.

Perhaps there is a molecular relative of nicotine that could be employed as
such, perhaps with less side-effects.

~~~
tcj_phx
> Also, there are several MAOIs in tobacco smoke. MAOIs are used as last-line
> anti-depressants, because of their side-effects when taken in large doses.
> But with tobacco products, a user basically gets a tritrateable MAOI.

Reversible MAOIs are safer than the irreversible ones:
[https://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor#Re...](https://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor#Reversibility)

There were some articles in the Boston Globe in 2000 that pointed out that the
SSRI Prozac was known to contribute to suicides. I think it was a mistake to
allow this drug onto the market.

> If we suddenly discovered nicotine today, I'm convinced that either it or a
> close chemical cousin would be a the next miracle drug for anxiety and
> depression.

Niacinamide (Nicotinamide) is somewhat similar to Nicotine.

    
    
      Considering these striking homologies, the craving for 
      nicotine might be due, in part, to a misplaced "hunger" 
      for the nutrient, vitamin B3, [...]

-[http://www.highfiber.com/~galenvtp/vtlnctnc.htm](http://www.highfiber.com/~galenvtp/vtlnctnc.htm)

~~~
matthewbauer
I've always wondered: how do they establish a drug causes suicide? I mean
they're not literally giving people suicidal thoughts. How do they make people
more prone to suicide?

~~~
cowpewter
As far as I'm aware, the currently prevailing theory is that many deeply
depressed people may be be having suicidal thoughts, but their depression is
also so strong that they don't have the energy and/or motivation to actually
go through with it. Apathy is winning. As the drugs start to lift you out of
the hole of apathy, you suddenly start to have more energy and motivation, but
you're still depressed. So you still are suicidal but now you have the ability
to go through with it.

~~~
tcj_phx
This sounds like an apologist's explanation for an inconvenient truth. Sounds
reasonable, but falls apart when confronted with actual data.

(Edit: I'm sure you were paraphrasing what you'd read somewhere.)

Here's a quote from the Boston Globe's 5/7/2000 article:

>> Three years before Prozac received approval by the US Food and Drug
Administration in late 1987, the German BGA, that country’s FDA equivalent,
had such serious reservations about Prozac’s safety that it refused to approve
the antidepressant based on Lilly’s studies showing that previously
nonsuicidal patients who took the drug had a fivefold higher rate of suicides
and suicide attempts than those on older antidepressants, and a threefold
higher rate than those taking placebos.

>> Lilly’s own figures, in reports made available to the Globe, indicate that
1 in 100 previously nonsuicidal patients who took the drug in early clinical
trials developed a severe form of anxiety and agitation called akathisia,
causing them to attempt or commit suicide during the studies.

\-- [http://ahrp.org/prozac-revisited-concerns-about-suicides-
sur...](http://ahrp.org/prozac-revisited-concerns-about-suicides-surface-
boston-globe/) (I don't know anything about this site, but I've read the quote
elsewhere so I'm sure it's a true copy of what the Globe actually printed).

~~~
cowpewter
Oh yeah, it was definitely just something I've heard a bunch of times, and not
something I'd personally looked up the research on. Thank you for the links.

------
derefr
This makes me wonder what the modern world would look like if all
"recreational drugs" suddenly disappeared, and so all the people who were
implicitly, unknowingly self-medicating for a mental illness by using
recreational drugs, suddenly weren't. What percentage of the population would
go from seemingly neurotypical, to perceivably mentally ill? How much more
common would conditions like schizophrenia be?

~~~
seizethecheese
Alcohol: Anxiety disorders

Marijuana: OCD

Caffeine: ADHD

~~~
losteric
Or just MJ for everything

~~~
tsomctl
If you can recommend a strain that helps with ADHD while still allowing you to
be alert and cognizant, I would really like to know. I've been looking for
years.

~~~
losteric
[https://www.leafly.com/news/strains-products/best-
cannabis-s...](https://www.leafly.com/news/strains-products/best-cannabis-
strains-for-focus-and-addadhd)

I have had the most success with vaping green crack at 210C. Oil concentrates
also work, but I tend to overshoot the functional sweet spot and end up
recreationally high.

Smoking was much harder to nail down. It worked occasionally, enough to
justify buying the vape... But the vape is way better.

------
anigbrowl
_“This defines a completely novel strategy for medication development,” says
lead author_

As someone with schizoaffective problems and raging ADHD, I find quotes like
this acutely annoying. I've _told_ every psychiatrist I'eve ever dealt with
about the experiential costs/benefits of smoking (and consuming various other
recreational drugs). They all nod sagely and say things like 'but smoking is
bad' (no shit Sherlock!) while making absolutely zero effort to measure or
help me track any of this. Every mentally ill person I've known has said much
the same thing. Of all the medical professionals I've ever dealt with,
psychiatrists are the laziest and least imaginative.

Edited to add that I quit tobacco ~7 years ago using chantix, which I
_totally_ recommend. Unfortunately my mental ilnesses have become harder to
deal with over the same period. The last time I reached out to my psychiatrist
he said he hadn't seen me in so long that he didn't have room in his practice
for me any more. What an asshole.

~~~
agentgt
I have never been addicted to cigarettes and do not smoke but I do chew
nicotine gum all the time for ADD (and yes there is a difference between ADHD
and ADD).

I took me a while to figure out that nicotine is a superior stimulant over
caffeine, adderall, ritalin and even chocolate extract (albeit chocolate was
surprisingly effective).

The big plus with nicotine is that it doesn't have the after downer that the
above stimulants have. Particularly adderall.. it honestly shocks me that I
was given that drug as a child.

The jury still seems to be out on how dangerous nicotine is (the actual
substance and not all the crap you get with tobacco products).

~~~
jayd16
>The big plus with nicotine is that it doesn't have the after downer that the
above stimulants have.

What do you mean by this? Caffeine withdrawal over nicotine withdrawal seems
like a no brainer to me with what I've seen from smokers, but I don't smoke so
I can't say first hand.

~~~
agentgt
As another commenter alluded to I was referring to the crash or hangover.

As for withdrawal I don't think I have ever felt it with nicotine but it might
be because I just don't ever do enough (the most pieces of gum I have had in
one day is 40mg of nicotine.. ie 10 pieces). I have had a nicotine hangover
with cigars but this is usually because alcohol is involved as well as I
believe cigars lower intake of oxygen (just a theory.. probably wrong).

Caffeine withdrawal is awful.. absolutely awful for me. Headaches for days. I
usually give up and pound 4 ibuprofen with a large cup of coffee.

------
thomasjames
For those who have seen severe mental illness up close, this is not surprising
in the least. Many, many people with schizophrenia or other disorders
characterized by psychosis self-medicate heavily with cigarettes. Huddled
masses of patients smoking outside are fixtures of most psychiatric treatment
facilities.

~~~
tlarkworthy
Well, its the same thing in prisons, so I always assumed its boredom/stress
relief as the explanation for chain smoking.

~~~
troygoode
Or it indicates that prisons also contain many mentally ill inmates...

~~~
bkmartin
Which they do, but it is really tough to unwind the correlation/causation
factors here.

------
eganist
Original DOI link:

[http://dx.doi.org/10.1038/nm.4274](http://dx.doi.org/10.1038/nm.4274)

Edit: Please read abandonliberty's comment below before reading mine. I didn't
properly elucidate the position on the harms v. benefits tradeoff (net harm)
the way abandonliberty did.

My own opinion: it wouldn't be terribly surprising to see many harmful
substances only be harmful to a majority subset of a population space, though
that's why the scheduling system (theoretically) exists -- to allow drugs to
be classified based on harm v. benefit to various populations. Whether
Nicotine should be scheduled is... well, given the number of people addicted
to it, probably not the easiest conversation to have. I originally thought it
was Schedule II (high abuse potential but with some medical benefit, which
would certainly fit our potential future understanding of nicotine based on
studies like this), but it turns out my original hunch was faulty googling.

~~~
abandonliberty
Clarifying: Nicotine harms everyone. Net harm to a schizophrenic may be
negative, but they are still harmed.

"Self-medication hypotheses" exist for many abused substances. Rather than
accusing the addicted of poor education, self control, or intelligence it
argues (with mounting evidence) that there is a structural or genetic issue
that contributes for some addictions.

Ideally we would figure out the mechanism of action and design something with
less negative life altering side-effects.

There's always an opportunity to examine freedom of choice/free will for the
more philosophic among us :)

~~~
codr4life
Bullshit. Nicotine in itself doesn't harm anyone, that's completely made up.
On the contrary, a lot of people would be helped by getting more Nicotine into
their system, preferably from eating veggies rather than smoking it.

~~~
abandonliberty
The burden of proof is on you here. If you're going to argue something at odds
with the medical profession and most published research, you better have some
solid facts from reliable sources.

~~~
surement
Keep in mind that most of this published research is about smoking cigarettes
(using "nicotine" as a metonymy).

------
BurningFrog
That Schizophrenia patients smoke a _lot_ is well known. I guess this explains
it.

The other weird Schizophrenia fact is that blind people are never
Schizophrenic. Congenital Blindness, that is. Poking your eyes out won't cure
Schizophrenia once you have it.

~~~
kruhft
> blind people are never Schizophrenic

That is an interesting observation. Do you have a source?

~~~
BurningFrog
[https://www.psychologytoday.com/blog/the-imprinted-
brain/201...](https://www.psychologytoday.com/blog/the-imprinted-
brain/201302/why-early-blindness-prevents-schizophrenia)

~~~
angry-hacker
Thank you, very exciting.

------
shock
Until the site recovers from the hug of death, here's a cache:
[https://webcache.googleusercontent.com/search?q=cache:http:/...](https://webcache.googleusercontent.com/search?q=cache:http://neurosciencenews.com/schizophrenia-
nicotine-brain-activity-5995/)

~~~
johnmarcus
thanks!

------
pizza
[https://en.wikipedia.org/wiki/Schizophrenia_and_smoking](https://en.wikipedia.org/wiki/Schizophrenia_and_smoking)

------
jessaustin
It won't really be a surprise, when science learns that _most_ "harmful
addictive" substances can improve aspects of brain function for many people.

~~~
mahyarm
Isn't it more the delivery mechanism than the drug itself?

~~~
rabidrat
After lung disease, the second largest consequence of tobacco smoking is heart
disease, which is due to the nicotine itself.

~~~
iak8god
It looks like about 1/3 of smoking-related deaths are due more to the nicotine
than the smoke:
[https://www.cdc.gov/tobacco/data_statistics/fact_sheets/heal...](https://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/tobacco_related_mortality/)

That's much higher than I'd assumed, and bad news for those who want to claim
that e-cigarettes are essentially safe.

EDIT: DanBC points out below[1] that it's wrong to assume the cardiovascular
disease is caused primarily by nicotine, which is how I came to think it was
about 1/3\. So I retract this interpretation, but leave it up for posterity :)

[1]
[https://news.ycombinator.com/item?id=13467235](https://news.ycombinator.com/item?id=13467235)

~~~
jdietrich
I couldn't find that evidence anywhere in your link. A report by Public Health
England estimated e-cigarettes to be at least 95% less harmful than
combustible tobacco.

[https://www.gov.uk/government/uploads/system/uploads/attachm...](https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/457102/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf)

~~~
iak8god
The report you linked does not explain the 95% number, and following their
citations bottomed out in articles that don't contain that number either. I'd
need to spend more time looking through those before I'd feel comfortable
saying _that no existence for the 95% harm reduction claim can be found in the
tree of citations spinning out from the PHE report_ , but please be aware that
as of now you have not provided evidence for that claim. I'd be pleased if you
would, since it would probably save me a lot of time later.

~~~
jdietrich
[https://www.gov.uk/government/uploads/system/uploads/attachm...](https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/456704/McNeill-
Hajek_report_authors_note_on_evidence_for_95_estimate.pdf)

~~~
iak8god
Thanks, this is more clear and straightforward about where they got that
number, though the relevant citation ends up being the same as in the longer
document.

The evidence cited in that summary is the study 'Estimating the Harms of
Nicotine-Containing Products Using the MCDA Approach'[1]. If you read that
paper, I guarantee you will find yourself much less confident in the 95% harm
reduction claim. Briefly, here's the method they employed:

* Convene a panel of "international experts" in a two day workshop. * Ask each participant to separately rate how harmful they believe each type of nicotine-containing product is, on a scale of 0 (no harm) - 100 (cigarettes). * Weight/average the scores and publish the results

In case anyone is inclined to think that counts as "evidence", be aware that
the authors of that study _don 't_:

"A limitation of this study is the lack of hard evidence for the harms of most
products on most of the criteria"

They fail to mention in particular the lack of long-term evidence for some of
the products, which have not been available long enough to properly measure.

In any case, I am aware that vaping nicotine is much safer than combusting
tobacco (though I think the latter is a lot yummier). However, I found this to
be an interesting case study in how a report can pull out precise and
scientific-looking numbers like 95% and trust that people for the most part
will take that at face value without looking into the scientific validity of
the claim.

[1]
[http://www.karger.com/article/FullText/360220](http://www.karger.com/article/FullText/360220)

------
TeMPOraL
Relevant SSC post on the topic:
[http://slatestarcodex.com/2016/01/11/schizophrenia-no-
smokin...](http://slatestarcodex.com/2016/01/11/schizophrenia-no-smoking-
gun/).

------
majkinetor
Might be because of niacin too, here is the informative article:

[http://www.orthomolecular.org/resources/omns/v13n05.shtml](http://www.orthomolecular.org/resources/omns/v13n05.shtml)

------
diogenescynic
I'm surprised that no one has pointed out that tobacco absorbs lithium from
the ground can be found in smoking tobacco [1]. Lithium is also used as an
anti-psychotic medication.

1: [http://www.europsy-
journal.com/article/S0924-9338(16)00128-0...](http://www.europsy-
journal.com/article/S0924-9338\(16\)00128-0/abstract?cc=y=)

------
hmahncke
Targacept was a biotech company that spun off from RJ Reynolds [1] with the
goal of making drugs related to nicotine that would help with schizophrenia
and other psychiatric/neurological disorders. They tried really hard, and it
didn't work [2].

[1] [http://www.prnewswire.com/news-releases/rj-reynolds-
tobacco-...](http://www.prnewswire.com/news-releases/rj-reynolds-tobacco-
company-announces-spin-off-of-targacept-73013932.html)

[2] [http://www.journalnow.com/opinion/editorials/editorial-
targa...](http://www.journalnow.com/opinion/editorials/editorial-targacept-a-
success-story-comes-to-an-
end/article_a7664424-c993-11e4-8005-6b7b4e23f8da.html)

------
eplanit
Maybe the movie Sleeper wasn't just a comedy:

[https://www.youtube.com/watch?v=D2fYguIX17Q&t=208](https://www.youtube.com/watch?v=D2fYguIX17Q&t=208)

------
yahyaheee
I've been thinking this for some time, nicotine is the only thing that make me
feel normal. You wouldn't think it would take so long to figure this out

------
eduren
Can anyone with access to the paper give a few technical details? The abstract
mentions "Chronic nicotine administration" does this mean the nicotine dosage
is high enough to not be a viable basis for treatment?

The linked article claims that this could be a basis for new drug research,
which sounds exciting, but how much do we already know about drugs that affect
the nicotinic receptors?

~~~
z2210558
I'm sure that means "smoking or equivalent".

------
protomyth
Ok, early days, but does this mean nicotine gum or vaping with an E-liquid
with nicotine could be used for Schizophrenia treatment?

------
adbge
This is at the intersection of several of my interests.

The idea that nicotine improves cognition in schizophrenia is not new and,
indeed, several drugs inspired by this idea (nicotinic agonists) are currently
in the pipeline for the treatment of ADHD, schizophrenia, and depression. [1]

In this paper, the researchers are focused on a polymorphism in the CHRNA5
gene. Pulling up my 23andme data, this mutation (rs16969968) looks common,
listed at 45% of the population. I have one of the "bad" alleles and,
personally, use nicotine as a stimulant every once in a while and find it more
effective than coffee but less effective than adderall.

If you are interested in this sort of research, I recommend getting part of
your genome sequenced with 23andme [2] and then running your data through
Promethease [3]. But, remember, don't take anything _too_ seriously -- most of
this isn't settled science.

There is also some evidence that nicotine may function as a "nootropic," i.e.
a drug that enhances cognition even in the healthy. Nick Bostrom mentions
using nicotine and caffeine to aid writing his book _Superintelligence_.

Contrary to what you might believe, nicotine is probably not all that bad for
you, or even that addictive when not used in combination with an MAOI. The
best review of this is, as usual, by Gwern. [4]

Finally, I want to mention a few other interesting properties of nicotine:

\- The drug seems to more strongly reinforce behaviors done while under the
influence of it than it reinforces "taking nicotine" (addiction). This may
make it useful for implementing positive habits. e.g. I often chew half a
piece of nicotine gum while running in an attempt to solidify my exercise
routine.

\- One study suggests that, at least in mice, nicotine administration results
in long-term upregulation of reward sensitivity. [5]

Huge disclaimer here at the bottom: if this post convinces you to experiment
with nicotine, please do not start with vaping. The near-instant reinforcement
of inhaling a stimulant makes it much more addictive. Stick with gum, or a
tincture. [6]

[1]
[https://en.wikipedia.org/wiki/Nicotinic_agonist#Current_stat...](https://en.wikipedia.org/wiki/Nicotinic_agonist#Current_status)
[2] [https://www.23andme.com/](https://www.23andme.com/) [3]
[https://promethease.com/](https://promethease.com/) [4]
[https://www.gwern.net/Nicotine](https://www.gwern.net/Nicotine) [5]
[http://www.nature.com/npp/journal/v31/n6/full/1300905a.html](http://www.nature.com/npp/journal/v31/n6/full/1300905a.html)
[6]
[https://www.reddit.com/r/Nootropics/comments/3lvkmc/nicotine...](https://www.reddit.com/r/Nootropics/comments/3lvkmc/nicotine_as_nootropic_the_cheap_and_safe_way/)

~~~
kr7
If I'm reading it correctly, the 'A' genotype is bad, for those who want to
check for themselves:

[https://you.23andme.com/tools/data/?query=rs16969968](https://you.23andme.com/tools/data/?query=rs16969968)

------
77pt77
Cached page:

[https://archive.is/riIDg](https://archive.is/riIDg)

------
alfon
I wonder if this could be related
[https://academic.oup.com/aje/article/155/8/732/65654/Parkins...](https://academic.oup.com/aje/article/155/8/732/65654/Parkinson-
s-Disease-Risks-Associated-with)

------
yarou
I've long suspected that nicotine has a net benefit effect on cognition.

I'm curious to see if there will be a new line of nACHr drugs that can
potentially enhance cognition.

