Nicotine is Not Evil: A Literature Review of Studies on Pure Nicotine

In a recent interview, the famous military strategist Edward Luttwak said:

“One book I’ve never written, is “The Impact of the Arrival of Nicotine and the Scientific Revolution.” A big jump in intellectual achievement that took place among those Europeans, all of whom smoked. The social history of nicotine begins with the sharpening of the brain.

He also thinks the west’s war on nicotine is making us all dumber.

Take away my nicotine patches, and I am immediately 5-10 IQ points stupider, which I can’t afford.

The contented grin of a man covered from head to toe in nicotine patches.

I’ve chewed 1 piece of 4mg nicotine gum about 5 days a week for close to 10 years, and I endorse Luttwak’s message.

But if you believe the medical establishment, we are both living recklessly. I was taught from a young age that nicotine is a toxic, deadly substance. And when tied to tobacco products, that appears to be the case.

But what about doing nicotine just a little bit, and never smoking it? I decided to research everything I could about pure nicotine to see if I should be scared off.

I was able to find plenty of research claiming nicotine is a horrific substance that only an idiot would willfully ingest. But when I dug deeper, I saw that all of the damning studies are really about using tobacco. I also noticed a surprising amount of research showing nicotine’s positive effects, such as how it helps with ADHD, irritable bowel disease, and Parkinson’s.

When it comes to studies claiming that nicotine is bad independent of smoking, I feel like Anthony Edwards when he was asked to comment on Rudy Gobert’s rim protection — they “don’t put no fear in my heart.”

In this post, I’ll show why.

This has nothing to do with nicotine, but I’m fascinated by the fact that they are teammates now. Edwards once said Kristaps Porzingis was a better defender than Gobert, lol.

What the scientific research has to say about nicotine

Tobacco and nicotine are so intertwined in the scientific literature that they are hard to separate.

Thankfully, amazing independent researchers like Gwern, a total hero of mine, walk amongst us. He did the hard research into pure nicotine and wrote up his results:

Much of the nicotine/​tobacco literature willfully conflates the two, leading to misleading attribution of the harm of tobacco to nicotine; many associations with harm are confounded by past or present tobacco use (eg. Kenkel ⁠et al⁠ 2020), but when pure nicotine is examined, as in patch/​GUM nicotine replacement therapy, the harms appeared minimal: like all stimulants, nicotine may raise blood pressure somewhat, and is addictive to some degree, but the risks do not appear much more strikingly harmful than caffeine or modafinil (and certainly appear less than the many commonly-used amphetamines).

Overall, I am personally comfortable using nicotine gum (but not vaping) once in a while, and have done so since 2011 without any noticeable problems or escalation in usage frequency.

Preach! 

I am not going to reinvent the wheel and analyze at all the studies that Gwern looked at. What I can offer is a more in depth analysis of some oft cited studies which supposedly prove that even pure nicotine is terrible for humans.

A closer look at a few claims about pure nicotine 

I’ll start with Harmful Effects of Nicotine by Mishra et al, 2015. It has been cited 278 times and appeared as the 5th ranked post when I searched Google Scholar for “nicotine effects”.

The paper is a review of 90 studies that claim to only look at pure nicotine. They come to the conclusion that even without the influence of tobacco, nicotine is extremely bad for you.

There is an increased risk of cardiovascular, respiratory, gastrointestinal disorders. There is decreased immune response and it also poses ill impacts on the reproductive health. It affects the cell proliferation, oxidative stress, apoptosis, DNA mutation by various mechanisms which leads to cancer. It also affects the tumor proliferation and metastasis and causes resistance to chemo and radio therapeutic agents.

Scary stuff! But I think it’s way overstating the negative effects.

First off, about half the experiments and studies cited by the Mishra paper involved animals. (I looked at the first 20 of 89 cited studies and extrapolated from there.)

Most dealt with rodents, but there was a wide variety of animals used. Dogs, cats, and rabbits are also in the mix.

A dog being forced to smoke to test if it would get emphysema. (source)
More smoking dogs.What is wrong with people. (source)

In my opinion the majority of animal studies are hot garbage. These papers get at my viewpoint:

But there are of course animal results that do translate to humans, so let’s carry on and see if the Mishra paper gives us anything to get worried about.

Giving baby mice tumors for fun and profit

Pour one out for all the laboratory mice (source)

I decided to pick a couple of the studies the Mishra et al paper uses to support its claims to see if they justify such strongly negative conclusions about nicotine. If they aren’t reputable, why should I trust the other 80+ studies in the review? Just having a bunch of studies doesn’t mean anything if they’re all weak.

One claim the Mishra review makes is that nicotine is a tumor promoter.

Following the citation for that claim leads me to a paper called Nicotine and Gastrointestinal Disorders: Its Role in Ulceration and Cancer Development by Chu et al., 2013. 

The Chu study says nicotine is a tumor promoter, but instead of showing the evidence that proves it, they merely state it as fact and cite yet another study to back up their claim.

The study they cite is called Nicotine promotes gastric tumor growth and neovascularization by activating extracellular signal-regulated kinase and cyclooxygenase-2 by Shin et al, 2004. 

This paper finds “a direct promoting action of nicotine on the growth of gastric tumors.”

Which indeed it does. But the methods of the study make me question its relevance to humans. 

Here’s how one would go about replicating what Shin and crew did:

  • Get a bunch of 4-6 week old mice
  • House them in individual chambers
  • Surgically inject cancer cells into their stomach lining 
  • Force the mice to drink either tap water, or water with extremely large amounts of nicotine in it
  • Wait three months
  • Kill the mice and look to see if they had tumors and how big those tumors were

Every mouse in the study got a tumor, so at least that bit of science is settled — injecting baby mice with cancer reliably gives them cancer. 

Next, they looked at how big the tumors were and found that the mice given nicotine had slightly bigger tumors than the mice that drank tap water.

So grateful it’s not my job to cut out the intestinal lining of mice and take pictures of it.


That’s not great. No one wants bigger tumors. But should we update our thoughts on the human use of nicotine because of this study? Ehhhhh.

Let’s talk dosing. The mice in the “high nicotine group” consumed about .8mg/day of nicotine. Given the mice weigh a mere 25 grams, they were taking in an astounding amount of nicotine for their body weight. It’s the equivalent of a 150 pound human consuming 2000mg/day of nicotine. That’s like smoking 80 packs of cigs per day, or chewing 500 pieces of nicotine gum per day! For three straight months!

I would not disagree with a scientific paper saying that chewing 500 pieces of nicotine gum per day for three straight months is bad for you. I just think it’s not quite relevant to the average person. And I might think the scientists making a mouse consume that much were slightly unhinged?

To continue with my skepticism, we are talking about isolated baby mice who were purposely given stomach cancer.

I do think that if you already have stomach cancer it’s probably not a great idea to ingest large amounts of nicotine every time you drink water for months at a time. I am not sure what this tells us about someone like me, a 35 year old cancer free person who does nicotine in small doses.

The problem is that when a review paper confidently states that nicotine promotes tumors, they don’t also say,

We think it promotes tumors because in a 20+ year old study performed on baby mice who had cancer injected into their bodies before being forced to consume the equivalent of hundreds of cigarettes worth of nicotine per day, the nicotine caused tumors 2mm bigger than those in a control group.

That would be a lot less convincing.

Did you know one of the animal right’s movements first major supporters gave the movement a lot of money because he was worried about being reincarnated as a draft horse? I kind of feel like that about lab mice. (image source)

more dubious nicotine studies 

So the first claim made by the Mishra review paper technically checks out. But it didn’t convince me, a human being and not a mouse in a concentration camp laboratory, to worry about my low-dose nicotine intake.

I decided to investigate another claim made in the Chu paper mentioned above. Remember that this paper is a load bearing pillar for some of the claims Mishra makes in their influential and highly cited review paper talking about how bad pure nicotine is.

In a section of the Chu paper titled Gastric Ulceration, Inflammatory Bowel Disease, and Pancreatitis the authors state: 

“Nicotine caused a reduction in gastric mucosal blood flow and mucus volume. Taken together, all these factors may partially explain why cigarette smoke and its components exacerbated gastric ulceration.”

To prove that claim, they cite a 2005 paper published in Nature called “Mechanisms of Disease: nicotine — a review of it’s actions in the context of gastrointestinal disease” by Thomas et al., 2005. 

The Thomas et al. paper is yet another review paper that looks at around 800 articles relating to nicotine and the gastrointestinal system. Notably, it does not say it’s trying to control for pure nicotine without tobacco smoke. But whatever, let’s set that aside for now.

The claim I am checking is “nicotine caused a reduction in gastric mucosal blood flow and mucus volume.” 

The only section on gastric mucosal blood flow in the Thomas paper states that “studies have provided conflicting results, but in some studies nicotine reduced gastric mucosal blood flow.”

Okay, kinda weird. That is quite a hedged statement. If you check out the paper they cite to make that claim, you get a sense of why.

The paper is by Cho et al. from 1990, The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats

I really don’t think this paper should be used as a strike against nicotine. Let’s look at why.

Maybe nicotine actually prevents ulcers and helps IBS?

To reset a bit, we are now 4 levels deep. Mishra et all was a meta analysis saying all nicotine is evil. They cite Chu et al. to back up claims, Chu et al. cites Thomas et al, Thomas et al. cites Cho et al. 

It’s like freaking Inception trying to keep it all straight. 

Leo thinking about whether his nicotine habit is ultimately good or bad.

The claim I’m investigating is whether or not nicotine reduces gastric mucosal blood flow (which I’ll refer to as GMBF from now on, like the paper does.)

The Cho paper does in fact conclude that, sometimes, nicotine reduces GMBF. But overall it finds that nicotine is more likely to increase GMBF!

Here are the last few sentences of the paper’s abstract:

It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its anti-ulcer effect.

Anti-ulcer effects! So while the Thomas quote (“in some studies nicotine reduced gastric mucosal blood flow”) is true to the letter, it completely fails to get at the core of what was found in the study they cite to support their claim. 

The claim was that a reduction in GMBF partially explains why nicotine makes ulcers worse. When you follow the trail of citations to their conclusion, the claim cashes out in a study saying the exact opposite of what the anti-nicotine study is suggesting.

I can’t say for sure that nicotine doesn’t exacerbate gastric ulceration in rats. But I feel pretty confident saying the study I looked at that purports to prove that it does cause gastric ulceration in rats says nothing of the sort.

I think this says a lot about the overall state of the anti-nicotine literature. 

That’s because in the end, their scary claims often end up looking a lot weaker, and sometimes will be completely contradicted by, the studies they cite to prove their point.

I also think it’s notable that Gareth Thomas, the lead author on the Thomas et al. meta review, has run another study showing that nicotine is “a safe oral treatment for people with inflammatory bowel disease.”

Is all anti-nicotine literature this flawed?

Maybe I missed the key anti-pure nicotine studies that produced meaningful results applicable to humans. I do admit that I am biased in wanting nicotine to be relatively harm-free, so that could have tainted my research.

I know that some people are worried that nicotine might be messing with our dopamine receptors, which seems bad? When I google “nicotine and dopamine receptors” and click first result that does not mention smoking, I land on an article that says:

Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related and unrelated to drug seeking and consumption.

That doesn’t seem great! Ah, but what is that I see in the very next line?

We investigated in mice… 

Ah, right. There are those mice again.

In this study, they “implanted osmotic minipumps subcutaneously to expose mice to continuous nicotine (Nic, 10 mg/kg/day) or saline (Sal) for 3 weeks.” Let me translate: They gave the mice a nicotine dose equivalent to an averaged sized human ingesting 170 pieces of 4mg nicotine gum per day, or around 20 packs of cigarettes worth, every day for 3 weeks.

I’m surprised they didn’t just drop dead. Instead, they seemed to have moved a little faster than the other mice, plus they “exploited” rewards more.

I can’t say that all the research is on mice given stupidly large nicotine doses. And I can’t say that nicotine won’t mess with your brain in a negative way. I can say that I remain unworried about 4mg doses.

Nicotine as wonder drug

Leo, deciding that the pros of tobacco-free nicotine outweigh the cons. Vaping still seems bad for your lungs though, fwiw 🤷

If you’re like me, you might now be convinced that low-dose nicotine is not that bad for you. But is it good? Potentially, in some cases!

Here are just a few of the many studies and popular science articles talking about the positive effects of nicotine. Editors appear to really like using the delightfully naughty “wonder drug” moniker in headlines.

I also take seriously the fact that basically every successful person I’ve read about who lived between 1800-1970 was an avid smoker, and thus consumed a lot of nicotine. Many of these people were supremely unhealthy on many levels, but they made huge contributions to the world.

I gotta think the nicotine buzz helped Thomas Edison with his creations and Mark Twain with his writing. Twain certainly thought so. He claims to have smoked 300 cigars a month, and once remarked:

If smoking is not allowed in heaven, I shall not go.

Mark Twain
He apparently started smoking at age 8?!

More personally, I used to have awful IBS symptoms from ages 7-25. When did they stop? Right around when I started using nicotine, which has been shown to help with irritable bowel type issues. 🤔

There are even people arguing that Nicotine isn’t addictive! This 257 page academic report from 2002 written by 2 Israeli Ph.D’s says that, “Nicotine is not an addictive drug and that the popularized equation of the addictive properties of nicotine and heroin has little to do with science.”

Gotta love science. You can always find a study saying something that makes you feel good.

The almighty Gwern on whether nicotine is a performance enhancer

Gwern appears to be as fascinated with nicotine as I am, because along the general nicotine research he did he also conducted a nicotine use self-experiment. It’s famous in the internet circles I inhabit. People tend to reference it when arguing that nicotine doesn’t actually improve mental performance when taken daily.  

I recommend reading the whole study, if for nothing else than to see a true master researcher at work.

I’m like, “Gum make Drew feel good.” Gwern’s like, “Let me do a blinded study with placebos and Ph.D level rigor to see if I do better on tests of cognitive function when I chew nicotine gum.”

Gwern doing Gwern things while studying nicotine intake

His thinks that the gum maybe gives him a slight boost in performance, but it’s kind of hard to say.

The greatly increased variance, but only somewhat increased mean, is consistent with nicotine operating on me with an inverted U-curve for dosage/​performance (or the Yerkes-Dodson law): on good days, 1mg nicotine is too much and degrades performance (perhaps I am overstimulated and find it hard to focus on something as boring as n-back) while on bad days, nicotine is just right and improves n-back performance.

He concludes by saying he’ll continue to occasionally use nicotine gum.

The main thing I question is that he’s measuring his performance in what amounts to a memory challenge.

I don’t do nicotine to improve my working memory. I do it because it makes activities, especially long form writing, a lot more fun and productive. When I’ve got that nicotine buzz going it feels like I can better make connections between disparate ideas, write jokes, think up metaphors, and stay on task. I feel more creative and energetic. I’m not claiming it makes me smarter, only that it helps me get started on tasks and feel more in a flow state while I’m doing them. Perhaps substances that boost the creative side of things don’t have strong effects on the memory game side of things. 

My next quibble has to do with dosage, a potential downside he acknowledges by saying ,“1mg may have too small effects to easily detect.”

To me, studying only 1mg of nicotine is kind of like studying how you’d feel on 3 ounces of coffee. I can definitely feel something on 1mg of nicotine, but it’s much different than how I feel on my standard 4mg. 

Finally, Gwern and I have much different brain chemistry, upbringing, beliefs, priors, and brain harmonics.

Gwern is really into anime. I’ve never watched anime, nor do I have a desire to. And I don’t think Gwern stays up late watching NBA playoff games and texting his friends when he thinks the announcers are saying something dumb. 

As much as I wish I was more like Gwern, he’s just another data point, and I am hesitant to trust his conclusions over my own experience when deciding what nootropics to take.

In my opinion, there’s no substitute for trying things out for yourself.

Still, I can’t rule out that what I feel when I do nicotine isn’t mostly the placebo effect. I should do Gwern’s experiment and find out. Maybe one day. 

More on my personal experience with nicotine 

Nicotine can have a heavy body load. It hit me hard the first time I tried it and I almost threw up. So watch out for that.

Tolerance wise, I certainly don’t feel the rush for as long and as hard as I used to. But I still feel it plenty, and enjoy it. My slightly diminished buzz hasn’t led me to escalate usage over the past decade.

Just as I drink about the same amount of coffee each day, I have not had much trouble sticking to 4mg (or less) of nicotine whenever i used it. I tried to go higher once when I was staying up late for work, but the effects didn’t scale.

I don’t feel I get a ton out of increasing the dosage. And I’m grateful for that! You can find a lot of stories online of people who get very addicted to chewing gum or vaping. If you are one of those people, unfortunately you should probably find a different drug of choice. I normally have a very addictive personality so I’m super grateful that hasn’t happened to me.

Nicotine withdrawals can be nasty, so I’m glad I haven’t gone through that either. Mason Hartman had awful withdrawals when she stopped using nicotine. Her negative thoughts around nicotine gum in general gave me a lot of pause around my usage when I first read them.

Then I realized she was on a whole ‘nother level than me when it came to her intake!

I’d bet that I’d be feeling rough going cold turkey after that amount of daily use, too.

I set two strict rules around my usage that I’ve broken only a handful of times over the last decade. 

  • Never more than 4mg in a day
  • I always have to write at least something before I do other tasks. So even if I’m taking it to knock out a bunch of boring work tasks I don’t want to do, I need to jot something down in my journal beforehand. I do this because I like writing and want to be doing more of it, and because it helps me feel like I am not slipping into the habit of mindlessly consuming nicotine. (I wonder if the fact that I do this around nicotine and not coffee shows how deep the anti-nicotine propaganda is still in my system.)

Speaking of coffee, I have experienced plenty of legit crashes when my morning caffeine wears off. I can definitely notice when a nicotine dose wears off, but it’s nothing like a caffeine come down. It’s more like, “Okay, back to normal now.” A bad caffeine come down, at least for me, is more like, “Ugh, everything sucks and I have no motivation now.”  I can also chew gum in the evenings and still sleep soundly that night whereas late night caffeine throws my sleep off.

The biggest thing for me is that nicotine gets me locked into a writing flow state like no other substance I’ve tried. With nicotine’s assistance I can basically always sit down for solid hour or more of focused writing and have a great time doing it. From what I can tell, I am far from the only one who finds writing and nicotine to go hand in hand.

Would we have The Hobbit or LOTR without JRR Tolkien’s tobacco habit?

Nicotine also gets me over general work roadblocks remarkably easily. I can knock out a whole bunch of annoying tasks I have been putting off, such as emails, on 4mg of gum. Mostly it helps me get started at all, an effect Gwern also acknowledges when talking about why he likes gum more than patches:

I find I need stimulants more for getting started than for ongoing stimulation so it is better to have gum which can be taken precisely when needed and start acting quickly.

When I take breaks I don’t get jittery, nor do I crave gum all day. Maybe I get a little more annoyed in the afternoons than usual, since I normally do the gum between 2-4 pm.

I also get hungrier and more fatigued without it. I don’t believe I gain weight when I take breaks but I also haven’t measured it that closely and I am generally in really good shape. 

I also have had times where I take nicotine and feel some minor chest pain and tightness. But I’ve also had that when not chewing gum! So, I dunno what to make of that.

I recently had a thorough health checkup and came out looking very healthy on all measures. This includes sperm count and quality, since I had to get that checked out as part of the IVF process. I only mention it because anti-nicotine crusaders absolutely love to say that nicotine is disastrous for sperm. Maybe for some (and probably for smoker!), thankfully not for me.

All in all, I feel fine about my level of consumption and I think I’ll be okay as long as I’m vigilant about not letting my usage escalate.

My parting thoughts on Nicotine

Nicotine seems fine in small doses and I like it. 

If future research proves me wrong, and all nicotine is bad, maybe I’ll become more dedicated to finding a nootropic stack that replicates nicotine’s effects with less risk. L-tyrosine seems like a promising candidate, and I’ve used that in place of nicotine several times recently.

I also can’t rule out that there is a downside to chronic use over many years, although after all my research I’d be surprised if the effects were any different than chronic caffeine use.

All in all, I hope that my nicotine doses are small enough to not cause harm. I can also justify my usage the way people justify doing any drug — the benefits of boosted mood and productivity outweigh the downsides, at least for now.

I hope we don’t find any new bombshell accusations against nicotine. Can’t the universe just lets me have this one? I don’t eat meat or drink alcohol, so it only feels fair.

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