Nicotine
On the benefits and lack of demerits of nicotine (research up to 2015)
In 201115ya, I became curious about nicotine gum/patches as a possible alternative stimulant to modafinil: its much shorter half-life makes it more useful for evenings or scenarios like needing a quick alert on a long drive. I looked briefly into the nicotine/tobacco research to see whether there was convincing evidence that nicotine on its own, without any tobacco or smoke-related delivery mechanism, is either more harmful than most stimulants or likely to lead to severe addiction to tobacco as a ‘gateway drug’.
The psychological effects of nicotine as a stimulant are long established by a scattershot literature, so there are possible benefits.
Cost-wise, 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. et al 2020), but when pure nicotine is examined, as in patch/GUM NRT, 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). Animal experiments are, like usual, highly ambiguous, of low quality, and of doubtful relevance to humans. There is little evidence from the NRT literature that ‘never-smokers’ like myself are all that likely to become highly addicted, and minimal epidemiological evidence of harm from NRT use over the past 3 decades it has been available.
‘Vaping’ is another story: few experiments have been done, and its popularity is recent enough that any harms are poorly understood other than it can’t possibly be remotely as harmful as tobacco smoking, and its delivery mechanism plausibly is much more addictive than gum/patch delivery would be.
Overall, I am personally comfortable using nicotine gum (but not vaping) once in a while; as of 2024, I have done so since 201115ya, at frequencies ranging from daily to monthly, using gum/patch/spray forms, and can stop for weeks or months without a problem.
One of the reasons tobacco became so popular in the 1600s, along with tea & coffee (for their caffeine), was that nicotine is a powerful stimulant. Obvious enough; it affects tons of systems. Less obvious is that nicotine has many beneficial effects (and these benefits may be related to anomalous smoking results1); the infamous deadliness of smoking would seem to be almost solely from the smoke, not the nicotine. Even less obvious is that nicotine itself may not be especially addictive, and its addictiveness is genetically modulated2. (If nicotine was all that was going on, why do smokers struggle so much with their transition to NRT en route to quitting entirely? And why do so many people use nicotine gum or patches occasionally for long periods without being addicted, or quitting easily?)
All of the harm seems to stem from tobacco, and tobacco smoking in particular; this is not necessarily obvious because almost everyone casually conflates tobacco with nicotine (especially public education programs3), treating them as a single synonymous evil I dub “nicbacco”. When someone or something says that “nicotine” is harmful and you drill down to the original references for their claims, the references often turn out to actually be talking about tobacco rather than nicotine gums or patches45. Other methodological issues include comparing to current smokers rather than former smokers or failing to control for the subjects being the sort of people who would begin such a societally-disapproved activity like smoking; the studies typically aren’t designed properly even for showing an effect: you need a study which finds deficits in smokers but not in non-smokers or former smokers (eg. et al 2011 or et al 2008/ et al 2012 although neither enables nicotine inferences since there was no nicotine-only control group). The 2019 United States outbreak of lung illness linked to vaping products offers a case in point of this prejudice: despite every sign pointing to adulterants added to illegal THC/marijuana vaping fluids by fly-by-night operators rather than nicotine (such as the decades of nicotine vaping by millions of people not causing them to land overnight in hospital ICUs), the outbreak has been used as an excuse to ban legal nicotine vaping fluids instead—which is like banning aspirin as a response to the opiate crisis because they’re both used for pain relief and they both come in pill form, and some OD victims also used aspirin recently, so that makes them pretty much the same thing, right?
Addictiveness
Since it’s the main concern, we’ll address it up front.
Wikipedia summarizes et al 2005 as “Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties” - the addictiveness coming from MAOIs (eg. et al 2000, et al 2006) & possibly other compounds present in tobacco; while there don’t seem to many human studies aside from the et al 2006 review on the observed inhibition in smokers (consistent with the MAOIs playing a role in addiction), there are a number of significant animal studies:
et al 2003, “Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors”.
et al 2005, “Monoamine Oxidase Inhibition Dramatically Increases the Motivation to Self-Administer Nicotine in Rats”
et al 2005, “Monoamine Oxidase Inhibitors Allow Locomotor and Rewarding Responses to Nicotine”
et al 2006, “Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats”
Reviews or discussion of human smoking & MAOIs include et al 2003 & 20016.
Another thorough and contrarian piece is Frenk & 2002 book, A Critique of Nicotine Addiction. I don’t entirely agree with their take-no-prisoners arguments, since additional work since 200224ya has clearly shown that nicotine alone does have some addictive properties: for example, Le et al 2007, “High Reinforcing Efficacy of Nicotine in Non-Human Primates” found that given enough development, squirrel monkeys would push levers up to 600 times for an injection. But on the other hand, as Le Foll et al comment:
Surprisingly, reinforcing effects of nicotine alone have often been difficult to demonstrate directly in controlled laboratory studies with both animals and humans as experimental subjects. Consequently, there has been continuing controversy in the literature about the validity of previous findings of reinforcing effects of nicotine in experimental animals and human subjects [3], [4], [5], [6], [7], [8].
Or “Brain science, addiction and drugs” 200818ya:
The results showed that 40% of smokers receiving the [anti-nicotine] vaccine gave up smoking for nearly six months of follow-up; the highest smoking cessation rate (57%) was associated with the highest antibody response. These results are better than those seen in most nicotine replacement trials, but it is interesting that an unusually high proportion (31%) of the smokers receiving placebo also quit smoking for up to six months [Holman J (200521ya). “Helping patients kick the habit”. American Diabetes Association, DOC News 2, 1-2].
My take away is that there is addiction but it’s drastically overestimated by almost everyone and may been conflated with the habit-formation capability; the latter makes nicotine doubly valuable, but the former means we will want to be more careful with the nicotine than with modafinil or caffeine, where the main consequence of carelessness is tolerance rendering the stimulant useless or messing up our sleep for a few days.
For example, snus, a sort of chewing tobacco, has been studied extensively in Sweden where it is very popular and has been credited with large reductions in the smoking rate7, and with little hard evidence of harm from snus use8. Smokeless tobacco in general is hugely more safe than smoking (“Smokeout: Not as easy as ABC”, Washington Times):
Modern smokeless tobacco products contain nicotine in addictive doses to satisfy smokers’ cravings. University research has documented that smokers who switch to smokeless tobacco reduce their risk for all smoking-related illnesses, including oral cancer. On average, smokers live 8 years less than those who never used tobacco; smokeless users lose just 15 days. Statistically, smokeless users have about the same risk of dying as automobile users.
Or “The Nicotine Patch Didn’t Work? You May Not Have Used It Enough”, The New York Times:
“People are unreasonably afraid of nicotine”, Dr. Shiffman said. “The majority of smokers believe that nicotine causes cancer and is a big player in the harm caused by cigarettes.” In fact, carbon monoxide, tar and the countless toxic particles in cigarette smoke are what promote illness. Although smokers may become dependent on nicotine, it does not appear to raise the risk of cancer, lung disease or heart disease. Early reports that people who smoked cigarettes while wearing a patch stood an increased risk of heart attack proved unfounded years ago.
On the e-cigarette regulation controversy:
Dr. Siegel, whose graduate school manuscripts Dr. Glantz used to read, says e-cigarette pessimists are stuck on the idea that anything that looks like smoking is bad. “They are so blinded by this ideology that they are not able to see e-cigarettes objectively,” he said. Dr. Glantz disagrees. “E-cigarettes seem like a good idea,” he said, “but they aren’t.”…Public health experts like to say that people smoke for the nicotine but die from the tar. And the reason e-cigarettes have caused such a stir is that they take the deadly tar out of the equation while offering the nicotine fix and the sensation of smoking. For all that is unknown about the new devices - they have been on the American market for only seven years - most researchers agree that puffing on one is far less harmful than smoking a traditional cigarette…E-cigarette skeptics have also raised concerns about nicotine addiction. But many researchers say that the nicotine by itself is not a serious health hazard. Nicotine-replacement therapies like lozenges and patches have been used for years. Some even argue that nicotine is a lot like caffeine: an addictive substance that stimulates the mind. “Nicotine may have some adverse health effects, but they are relatively minor,” said Dr. Neal L. Benowitz, a professor of medicine at the University of California, San Francisco, who has spent his career studying the pharmacology of nicotine…“Part of the furniture for us is that the tobacco industry is evil and everything they do has to be opposed,” said John Britton, a professor of epidemiology at the University of Nottingham in England, and the director for the U.K. Center for Tobacco and Alcohol Studies. “But one doesn’t want that to get in the way of public health.”
(Specifically, the main carcinogens in tobacco seem to be the nitrosamines, polycyclic aromatic hydrocarbons, radium-226, polonium-210, and the nanoparticles like carbon created in combustion; see 1986, 2004 & National Cancer Institute. That is, smoking is bad for you for much the same reason that fireplaces kill; see et al 2007.)
Which would seem to suggest the following line of thought: if the research on actual smoking is equivocal, and then the demonstrated harm of non-smoking tobacco is so minimal (even if we ignore equivocalness), then how much safer would be just nicotine on its own as a patch/pill? Let’s ignore the general issue of tobacco (about as harmful as TV watching?910) and focus on just nicotine.
Effects
Benefits
Performance
If you’ve read through this page and also read the Wikipedia page on nicotine, your eye was probably caught by the mention that nicotine affects the cholinergic system - the same system piracetam affects. (This might make nicotine redundant with piracetam or other nootropics that affect acetylcholine or acetylcholinesterase, such as huperzine-A, but it’s been argued against.11)
Indeed, the research literature is full of results connecting nicotine with improved mental performance:
nicotine boosted IQ scores in a small sample of smokers, specifically scores on the RAPM12 (possibly related to its increasing global connectivity since IQ is being increasingly reified as measuring the global connectivity of multiple brain subsystems), although et al 2018 finds that nicotine merely makes their subjects faster at reaction-time tasks but not IQ tests
reaction time is improved, as is inspection time and visual search (but perhaps due solely to faster motor reaction?)
pilots’ performance enhanced 4⁄5 as much as donepezil does; improves late-day piloting
overnight performance on various memory & attention13 tasks (“These data suggest that when performance is being measured overnight, smokers show little or no impairment, whilst the performance of non-smokers showed performance decrements.”)
faster performance on Stroop and word classification
in smokers, improved prospective memory (things one intends to do); et al 2005
can improve handwriting
helps ADHD ( et al 1996; or et al 1996 - as well as OCD, see previous footnote): “Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy.”
may help symptoms of schizophrenia via increased synthesis of GABA & increased effectiveness of cognitive training (see Wikipedia), and protect against Parkinson’s & Alzheimers, see 200016 but note the difficulties in dealing with mortality bias (or just general cognitive impairment in the elderly)
A meta-analysis of nicotine studies reports results similar to older literature reviews (eg. 1992, et al 2004):
There were sufficient effect size data to conduct meta-analyses on nine performance domains, including motor abilities, alerting17 and orienting attention, and episodic and working memory. We found significant positive effects of nicotine or smoking on six domains: fine motor, alerting attention-accuracy and response time (RT), orienting attention-RT, short-term episodic memory-accuracy, and working memory-RT (effect size range = 0.16 to 0.44).
A 201115ya ADHD review18 covers nicotine:
Dozens of studies have assessed the effects of nicotine on cognition in healthy, nicotine-naïve samples including studies of memory ( et al 2003), attention ( et al 2009) and inhibitory control (Potter and Newhouse, 200422ya). In a recent meta-analysis of 48 studies in which nicotine was administered to non-smokers or only minimally deprived smokers ( et al 2010), nicotine was shown to have positive effects on multiple domains including attention and working memory. Twenty-nine studies specifically assessed non-smokers and among those, positive effects were observed for reaction time on tests of sustained (or alerting) attention and working memory.
Studies of the effects of nicotine on inhibitory control were not included in the meta-analysis, but a handful of studies suggest potential positive effects of nicotine on this domain. Two small studies have observed acute ( et al 1998) and chronic ( et al 2006) transdermal nicotine administration to result in trends toward decreases in errors of commission on a CPT task. Moreover, nicotine has been shown to reduce CPT commission errors in nonsmokers with schizophrenia ( et al 2007), non-smokers low in attentiveness (Poltavski and Petros, 200620ya); and decrease stop signal reaction time in adolescents nonsmokers with ADHD (Potter and Newhouse, 200422ya). Despite these findings, nicotine was not shown to improve response inhibition in adults with ADHD as measured with a CPT task ( et al 2001).
nicotine confirmed to have short-term boosts to “attention and memory”19; similar results (with one negative20):
et al 2003, “Cognitive effects of nicotine in humans: an fMRI study”,
et al 1996, “Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers”
et al 1994. “Nicotine and smoking: a review of effects of human performance”
Le et al 1994 “A low dose of subcutaneous nicotine improves information-processing in non-smokers” and “Effects of cotinine on information processing in nonsmokers” (cotinine is a nicotine metabolite with effects of its own)
during withdrawal, performance returns to baseline (but not below; in tension with 2011, and see also a similar possible example with neuroplasticity)
In non-humans, mice learn faster on low doses (see also et al 1998, “Nicotinic acetylcholine involvement in cognitive function in animals”)
perhaps unsurprisingly given all this, nicotine has been found helpful in the elderly; see “Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial” (slides; mention no withdrawal symptoms)21 and its citations. (In keeping with our usual nicotine vs smoking dichotomy, note that smoking may be bad for mental functioning in the elderly22.)
expectancies don’t seem to be a large part of the effect
but doses past 14mg seem to harm performance in et al 2012
Notice that many of these results are recent, and postdate the victorious war on tobacco. The question of whether positive results are tainted by tobacco money has been examined; Anders Sandberg notes that there is pretty clear evidence of funding bias - but the independent researchers still turned up their fair share of positive results.
Anecdotally, a great many Imminst posters report a positive experience which is similar to, but better than, the extremely popular amphetamine formulation Adderall; a few also favorably compare it to caffeine. (These anecdotes are supported by a historical survey which reports that the 2 highest rates of hourly consumption were during work hours, and that “Of these three groups [surveyed], 86% of the clinic group, 83% of the students, and 59% of the hospital workers agreed with the statement that ‘smoking helps me think and concentrate’.”)
Habit-Formation
Besides the nootropic effects, nicotine can be used as an relatively precise self-reward - faster acting than other stimulants like caffeine and modafinil, but with a combination of weak addictiveness and habit formation which is seems to be neural23 and epigenetic24 and affecting sensitivity of the reward system. This use of nicotine to strengthen habits is in accord with at least some research into nicotine; from “Nicotine Creates Stronger Memories, Cues To Drug Use”, Science Daily, describing “Dopamine enables in vivo synaptic plasticity associated with the addictive drug nicotine” (2009; see also 2008, et al 2011, et al 2017):
“Our brains normally make these associations between things that support our existence and environmental cues so that we conduct behaviors leading to successful lives. The brain sends a reward signal when we act in a way that contributes to our well being,” said Dr. John A. Dani, professor of neuroscience at BCM and co-author of the study. “However, nicotine commandeers this subconscious learning process in the brain so we begin to behave as though smoking is a positive action.” Dani said that environmental events linked with smoking can become cues that prompt the smoking urge. Those cues could include alcohol, a meal with friends, or even the drive home from work. To understand why these associations are so strong, Dani and Dr. Jianrong Tang, instructor of neuroscience at BCM and co-author of the report, decided to record brain activity of mice as they were exposed to nicotine, the addictive component of tobacco.
…“The brain activity change was just amazing,” Dani said. “Compared to injections of saline, nicotine strengthened neuronal connections-sometimes up to 200 percent. This strengthening of connections underlies new memory formation.”…“We found that nicotine could strengthen neuronal synaptic connections only when the so called reward centers sent a dopamine signal. That was a critical process in creating the memory associations even with bad behavior like smoking.”
I have had success working around ‘Ugh’ reactions to various activities. I took the direct approach. I (intermittently) use nicotine lozenges as a stimulant while exercising. Apart from boosting physical performance and motivation it also happens to be the most potent substance I am aware of for increasing habit formation in the brain…
And I do use nicotine for studying at times (usually patches that I have cut into the desired dose). Partly for learning mental habits and partly for enhanced focus and motivation without the agitation that comes (with methamphetamine (at least, for me)). Again, I don’t swear by it but it works…25
I have never smoked a cigarette. Nor have I ever had a remote tendency towards addiction to any substance. That is even one of the reasons I gave when describing why this is an effective technique for me personally. I am more at risk of becoming addicted to discussing substances on the Internet than the substances themselves….
I should note that the role nicotine lozenges are taking here is not primarily as a training reward, like giving the rat electronically stimulated orgasms when it presses the lever. Nicotine isn’t particularly strong in that role compared to alternatives (such as abusing Ritalin), at least when it is not administered by a massive hit straight into the brain via the lungs. No, the particular potency of nicotine is that it potentates the formation of habits for activities undertaken while under the influence by means more fundamental than a ‘mere’ stimulus-reward mechanism. Habits that are found to be harder to extinct than an impulse to take a drug. This is what makes smoking so notoriously hard to quit even with patches and makes the use of fake cigarettes to suck on useful.26
(I found 1mg nicotine gum helpful for starting a gym-going habit, but then after it felt strong, I dropped it due to a bit of concern about increasing blood pressure before strenuous workouts.)
E-cigarettes are a really cheap nicotine delivery system. Like pennies per cigarette equivalent cheap if you mix juice yourself. I don’t see how taking advantage of the effects of nicotine is any worse than caffeine. I started vaping while I study and have seen huge productivity improvements from the reduction in ugh fields.
Dose-wise:
My lozenges (when I had them) were 4mg… which I would consider almost too much. About equivalent to a full double-dose can of energy drink. If I use nicotine as a stimulant now I tend to go with about 4mg of 16 hour patch. (That is, I cut the 24mg 16 hour patches into small pieces).
Costs
Price
The price is not an issue. Nicotine in the US is not as expensive as one might intuitively guess from sky-high cigarette prices & widespread tobacco smuggling; perhaps due to the intrinsic low cost of nicotine or because it is politically unpalatable to tax products which are largely used by people quitting smoking, prices for a 2mg dose of nicotine is easily in the 15-20 cents range:
for example, one Nicorette gum product offers 100 4mg gums for $57.88$38.562013, or 39 cents a gum, or if you split one in half to get a 2mg dose, $0.27$0.182013 a dose.
a random nicotine lozenge product is 144 4mg lozenges for $64.07$42.682013, $0.45$0.32013 per lozenge, and $0.23$0.152013 per 2mg.
2mg may be too much for a non-smoker like me, in which case prices per dose drop further. Nor have I looked hard27 for low prices; just grabbed random hits on Amazon. You could probably drive it down to the 5-10 cents range with canny shopping and buying in bulk (nicotine is an insecticide, not a perishable foodstuff, so you could buy years’ worth - just like with melatonin). One difficulty with gum, however, is that it’s hard to subdivide: nicotine evaporates from gum and so cutting up a 4mg piece of gum into 4 1mg pieces forces you to either use them all within a few hours, waste some pieces, or store them in some sort of air-tight wrapper for later use.
Further, the rise of e-cigarettes which use nicotine dissolved in water means that if you are willing to have the nicotine absorbed quickly (which would seem to slightly increase addiction risks), the price for a 2mg dose plummets even further; consider one liter of fluid for e-cigarettes ($353.48$2322012 as of 201214ya, but down to $240.18$1602013 as of October 2013). The concentration is 100 mg of nicotine per ml, there are 1000 ml per liter, one wants 2 mg per dose, so (100 × 1000) / 2 = 50,000 doses for $348.25$2322013, or a (very) small fraction of a cent per dose
Health Issues
So, what are the gotchas?
Tolerance may be a problem. Posters report (like with most stimulants, and perhaps modafinil); their anecdotes are supported by general observations that smokers tend to escalate their smoking habit and by findings that nicotine down-regulates its receptors in mice.
On the other hand, even if one does develop tolerance to nicotine, that simply suggests spacing it out or rotating with other stimulants. One could imagine a 3-day cycle: nicotine, caffeine, and modafinil.
Nicotine is well-known to cause vasoconstriction (higher blood pressure) which concerns people
But the increase may not be all that large, especially at a low non-smoker dose; and if there is blood pressure increase, it may be perfectly tolerable.28
Though patches are generally found to be safe29 and not abused30, research on nicotine turns up all sorts of possible ways nicotine could be net-unhealthy (perhaps it metabolizes to a carcinogen among other things or cause mutations31 )
But nicotine has been so intensively studied that we ought to expect a lot of scary looking correlations and possibilities even if nicotine were the bee’s knees, and it can be difficult to interpret the overall mass of studies - what does it actually mean if in mice nicotine increases lung cancer resistance but in female rats nicotine plus estrogen weakens resistance to brain trauma? Does this work in humans? Does it make the cancer more deadly? Is that offset by benefits elsewhere? Is this even a real result given the small sample sizes & lack of replication? If we read of massive carcinogenesis in mice being given LD50-size doses of nicotine for 2 years, is that evidence against nicotine’s safety or for? What does it mean when one can cause cytotoxicity in mouse cells in a petri dish using 100% undiluted nicotine (and no more dilute) while 4/5 cigarette smoke extracts caused cytotoxicity? There are a lot of links in this page, but only a fraction of the ones I’ve seen. Cherry-picking and unjustified leaps are a problem in any review; “Cigarette smoking: an underused tool in high-performance endurance training” makes the point humorously. One Mind & Muscle illustrates the problem: “Consider acne. Nicotine increases keratinocyte differentiation, increases sebum production, etc. It seems like it would induce acne. Yet, overall studies show nicotine use is associated with significantly less acne, purportedly due to other anti-inflammatory mechanisms…nicotine is unfortunately far more complex and difficult to understand.” There are other grab-bags of pros and cons to nicotine32.
Nicotine has been shown to impair neurogenesis in the hippocampus in rats at high doses.
But the impairment was only shown at the higher doses33, and it’s unclear how it would generalize to humans. (As well, many stimulants impair the hippocampus in mice & rats; caffeine, for example.)
there may be an interaction with diabetes: a small correlational study found a long-term correlation between nicotine gum and hyperinsulinemia & insulin resistance (an experimental rat study found the opposite); and et al 2001 found a short-term effect but only in diabetics, similar to et al 2004’s no acute effect in its (all-healthy) volunteers. (Unfortunately, most studies published since 199630ya citing et al 1996 in Google Scholar are focused on tobacco products or smoking.)
You could become addicted despite everything. Hypothetically, this could then lead to tobacco use with all the attendant ills.
This is a truly subjective one. Former smokers probably should not be monkeying about with nicotine. Some people are scared this might happen; others aren’t worried at all. Given what I’ve read about nicotine not being addictive but strengthening habits (see previous quotes from Wedrifid), I think this fear might be overblown.
Dependence
Nicotine gum or patch use seems to be extremely rare among people who have not previously smoked (“never smokers”), which makes it hard to judge the risk of developing dependence, or the risk of developing dependence and then moving on to tobacco.
An example of the rarity comes from et al 2008: the authors examined a survey of n = 28,000; 8 never-smokers claimed use of nicotine-replacement therapy, but 6 self-reported tobacco use or had blood-levels too high or low - leaving just 2 (probably) valid examples.
2007 ran an online (self-selected) survey on a smoking cessation website, receiving 848 responses; the 5 never-smokers (1 had smoked cigarettes before), reported dependence and one described it as self-medication for depression (see also et al 2013). 2007 described the background information on the rarity of never smokers, apparent absence of nicotine gum abuse, and generally low levels of dependence on former or current smokers:
People who were addicted to the nicotine gum could easily find our questionnaire, because it was listed on top of the list in Google. In spite of this effective enrolment strategy, we identified only two never-users of tobacco among daily gum users, which suggests that NRT use in never-users of tobacco is a rare phenomenon. Similarly, a previous survey in people who responded to a newspaper ad that read: “Are you addicted to nicotine gum?” could not enrol any never smoker [5]. Furthermore, there was no report of subsequent nicotine dependence in never smokers who were treated with nicotine for ulcerative colitis, aphtous ulcers and sleep-disordered breathing [18,19,20,21]. The short-term effect of the nasal spray was also tested in never smokers, with no report of never smokers getting addicted to this fast delivery product [22,23,24]. In a previous survey, 0.3% of adolescent never smokers reported past daily use of NRT, but none was reported as being addicted to NRT [25]. However, some adolescents will endorse using any product when a list is presented to them, eg. 0.4% said they used a fictitious nicotine “Nic-T” product [26]. In two surveys in the USA, 2.7% and 4.6% of school drug counsellors indicated that nicotine patches and gums were abused by adolescents, but these “NRT abusers” were mainly smokers who used NRT while smoking, and only 7% to 16% of these “NRT abusers” were never smokers [27]. The latter study did not report any case of NRT dependence in adolescent never smokers [27]. Similarly, studies in representative samples of the UK and Swedish general populations found no never-user of tobacco among users of NRT [28]. A review of post-marketing surveillance data in the USA found no report of primary dependence to the nicotine gum and patch,[29] and only 39 cases of dependence on the nicotine gum were reported per million prescriptions to smokers, in surveillance data [30]. Therefore, addiction to nicotine gum in never smokers is probably very rare. Furthermore, there may be few adverse consequences of being addicted to the nicotine gum, except for the financial cost and the inconvenience of permanent chewing. In particular, NRT products are safe even in patients with heart disease, [31,32] and there was no untoward effect of 5 years of nicotine gum use in the Lung Health Study [33]. Thus, long-term use of NRT is not known to be harmful.
2009 yielded additional information:
For instance, in U.S. national samples, 5 to 6% of nicotine gum users used it for more than the recommended duration of 3 months ( et al 2000; Shiffman, Hughes, Pillitteri, & Burton, 200323yaa), and in the UK, 9% of gum users in smoking cessation clinics used the gum for one year or more (Hajek, McRobbie, & Gillison, 2007). In a survey of 805 households that purchased the nicotine gum, 2% purchased it continuously for 6 months or more ( et al 2000). In clinical trials, up to 30% of patients use NRT products beyond the recommended 3-month period (Hajek, Jackson, & Belcher, 1988; Shiffman, Hughes, Di Marino, & Sweeney, 200323yab; et al 1991a; Steinberg, Foulds, Richardson, Burke, & Shah, 2006; Johnson, Hollis, Stevens, & Woodson, 1991; Hatsukami, Huber, Callies, & Skoog, 1993; Hughes, 1989). However, participants in clinical trials usually receive the gum for free, and having to pay for it decreases utilization (Hughes, Wadland, Fenwick, Lewis, & Bickel, 199135yab).
…Taking a substance over a longer time than intended is a criterion for drug dependence (American Psychiatric Association, 199432ya), but long-term use does not necessarily imply dependence, because dependence requires other criteria, in particular unsuccessful attempts to quit and withdrawal symptoms upon cessation. Post-marketing data from the U.S., reported by the manufacturers, indicated that only 39 cases of dependence on the nicotine gum were reported per million prescriptions ( et al 1996). However, the limitations of post-marketing surveillance data are well known (Brewer & Colditz, 1999), and survey data indicate that the prevalence of dependence on the nicotine gum in over-the-counter settings is substantially higher than that, at about 1% of ever users ( et al 2004). About one third of smokers report having ever used NRT products (Al-Delaimy, Gilpin, & Pierce, 2005). Thus, even if only 1% of users became dependent on the gum, this would still represent tens of thousands of people…Even though some users may be dependent on the gum, it must be emphasized that there is no known adverse consequence of long-term use of NRT, except for the financial cost, and that the potential benefits (ie. prevent late relapse) far outweigh the drawbacks. This is probably why dependence on the nicotine gum has been generally downplayed in the literature ( et al 2000 [see also et al 2005]).
et al 2011 found new e-cigarette users claimed large reductions in smoking due to e-cigarette use.
2011 found their e-cigarette users likewise used it as a smoking substitute.
et al 2013 ran an online survey of 1347 e-cigarette users; only 2 respondents were never-smokers and were not analyzed further. The current & ex-smoker respondents indicated less cravings & dependence on e-cigarettes than cigarettes, and to use them long-term as a substitute.
A 2016 survey by Scott Alexander of the online nootropics communities (primarily Reddit’s /r/nootropics) had ~342 respondents on its nicotine-efficacy question and a subset answered questions about nicotine source & whether they considered themselves addicted, but not never-smoker status:
About 35% of users reported becoming addicted, but this was heavily dependent upon variety of nicotine. Among users who smoked normal tobacco cigarettes, 65% reported addiction. Among those who smoked e-cigarettes, only 25% reported addiction (and again, since there’s no time data, it’s possible these people switched to e-cigarettes because they were addicted and not vice versa). Among users of nicotine gum and lozenges, only 7% reported addiction, and only 1% reported major addiction. Although cigarettes are a known gigantic health/addiction risk, the nootropic community’s use of isolated nicotine as a stimulant seems from this survey (subject to the above caveat) to be comparatively but not completely safe.
One approach to estimating addictiveness of nicotine gum or patches is to borrow a strategy from 2012 in looking at the success of various studies’ control groups (using nicotine gums or patches) in quitting during those studies:
The intention here was not to estimate the effect of the treatment but rather its placebo to determine how difficult it is to stop using a certain form of tobacco/nicotine product. Therefore, the success rate in the placebo group is used as indicators for difficulty abstaining. Table 2 shows that cigarette smokers, independent of treatment, show a success rate of roughly 10% with little variation (range 9.8-11.2). Those seeking to stop ST use have roughly more than double the success rate of cigarette smokers (range 19.1-33.0). In the study (Tønnesen & Mikkelsen, 2012), where 69 long-term users of pure nicotine mostly in the form of gum, in average seven years, a success rate of 36% was observed. Those who become long-term users of nicotine replacement therapy (NRT) are recognized as heavy dependent smokers (Hajek, Jackson, & Belcher, 1988), which also seemed to be true in this study. Their cigarette consumption before quitting was 24.5 per day and their recalled FTCD score from when they were smoking was a high 6.7. It can be hypothesized that this type of smoker would have had no better success rate in stopping than the 10% seen normally but when coming off long-term NRT, it was 36%. The 36% was obtained from a 1-year follow-up. Several of the smokeless studies reported success rates from 6 months. It is of interest to note that the authors excluded long-term patch users since it would have been unlikely to see a difference between active and placebo treatment due to the ease by which they normally can stop. Moreover, it is much more infrequent to observe long-term patch use (Shiffman, Hughes, Pillitteri, & Burton, 200323ya). It seems as a patch is not very likely to be able to support a compulsive use pattern due to its little behavioral involvement and or pharmacokinetic nicotine uptake pattern. The data in Table 2 lead us to conclude that quitting cigarette smoking is more difficult than quitting ST (Fagerström, Gilljam, Metcalfe, Tonstad, & Messig, 2010) and, although there is only one study from the NR category, that quitting these products may be easiest (Tønnesen & Mikkelsen, 201214ya).
What does this imply for any never-smoker (not predisposed to tobacco use) using nicotine gum/patches judiciously and self-monitoring for signs of dependence, well aware of the dangers of tobacco use? Given the lack of observations despite large datasets, the low rates of dependence in smokers, the ease of quitting nicotine gum, and so on, my personal opinion is that the risk of dependency should be much lower than the smoker risks of 1-20% and then the risk even lower of then progressing to tobacco use. (In considering cost-benefit, it’s worth remembering that tobacco use has been quit successfully by many millions despite the notorious difficulty, and that the health outcomes of quitters gradually heal to the baseline of non-smokers.)
Conclusion
So what’s the upshot? My reading has convinced me to at least give it a try and it has been useful (see the nicotine section of Nootropics). The negatives universally seem to be long-term negatives, and even if nicotine turns out to be something I haul out only in a crisis or every few weeks, it would still have been worth investigating.
External Links
Appendix: On Proving Too Much
Some people do try to argue that smoking is good for you. Are they right? I don’t know. As deliciously contrarian as it would be to go around shocking people by seriously advocating tobacco use, it’s not a subject I’m interested in tackling. In philosophy, one is taught to not “try to prove too much” (inviting people to modus tollens your modus ponens), to not do more philosophy than one has to; in programming, you learn to not become an “architecture astronaut” solving some hugely abstract version of your actual problem - such overreach invites disaster.
It’s much easier for me to defend use of nicotine, so that’s all I try to do: nicotine is pretty much harmless, the studies are clear, the relevant areas & studies comprehensible with not too much work, and I feel I can discuss it with a clean conscience. Really, about the worst you can say about pure nicotine use is that it might be a gateway to tobacco or that one’s blood pressure might increase, which are issues that can be easily addressed empirically via additional studies/surveys or by eg. measuring one’s own blood pressure after taking nicotine, respectively.
But if I wanted to defend tobacco itself, I have abruptly expanded my task by orders of magnitude: now I need to deal with all the anti-smoking correlational studies, I need to defend an idiosyncratic interpretation of how the tobacco industry’s products have evolved over the last century, I need to defend not just nicotine but all the other substances in tobacco which might override its benefits, I need to explain why the nigh-universal consensus against tobacco is wrong and to give a historical account of how such an error could come into exist and then expand to be universal. This is an incredible amount of work; any one of these points represents more work than this entire article and plausibly more work than this entire site. One could (and men have) spent entire careers working on small parts of the puzzle just outlined.
It’s also bad from the rhetorical point of view: defending tobacco requires me to engage in what looks like partisan politics & revisionist history. It is challenging beliefs that are, rightly or wrongly, deeply entrenched. Many people have enough flexibility to think, even if a relative died horribly of lung cancer, that nicotine was only the addictive stimulating agent and the real killer was the smoke or the tar or something, and so are willing to consider that nicotine - on its own - might be useful. They are not willing to consider the whole package.
You can see the difference in the tasks by comparing this one page to the multiple threads in Imminst alone with scores of pages in each. One is short and clear and easily evaluated on its own terms (I hope), and has met with neutral or positive reactions from everyone I’ve asked to read it; the other comes off as a crank laying out an entire worldview, filled with ad hominems, bad faith, and clearly has not changed anyone’s minds.
Remember Pareto’s observation about where most of the value in a subject comes from, and the value of your time! Without reason to believe tobacco has absolutely massive gains compared to nicotine alone (which there isn’t, even taking pro-tobacco claims at face value), it’s a very bad use of time to investigate tobacco. One should let sleeping fags lie.