Is nicotine 'addictive'? Probably not. No one can make definitive statements on this as there has never been any published research in humans. No clinical trial specifically to examine the potential of nicotine to create dependence in people who have never consumed tobacco has ever been published.
There is currently no evidence that it is dependence-forming unless/until it is delivered in tobacco, and especially in cigarette smoke, which is presumed to cause some sort of chemical change in the brain. After smoking tobacco, especially in cigarettes, people may become addicted to smoking and dependent on nicotine. Since there are 9,600 other compounds identified to date in tobacco/smoke, with multiple candidates for potentiators in that mix, it is believed that the synergy of multiple compounds causes a persistent brain chemistry change.
Nicotine, however, is a normal, natural part of the diet and everyone tests positive for it. Because nicotine is well-demonstrated to have prophylactic and treatment functions for neurodegenerative, auto-immune and inflammatory diseases and some cognitive function disorders, it is clearly an active component in the diet with positive and preventative functions - i.e. a nutrient.
There are multiple published clinical trials investigating the positive effect of nicotine supplementation on such conditions, which by definition need to employ never-smokers. Without exception, all report that of the hundreds of subjects who had large quantities of pure nicotine administered to them daily for up to six months, no person ever exhibited the smallest sign of dependence: no withdrawal symptoms, or reinforcement, or continuation of use in any form after the trial finished.
It is impossible to clinically demonstrate any potential for dependence for pure nicotine with never-smokers, no matter how much is given or for how long.
Neither is nicotine associated with cancer or any other disease. There are clearly significant financial and other benefits to maintaining the illusion that nicotine is addictive and harmful, since otherwise such a strong campaign to protect this perception would not be sustained.
Potential dependence in 'paired nicotine' delivery systems is a recent topic of research. There have been several reported cases of dependence on nicotine chewing gum; though dependence potential is clearly at statistically invisible levels. More detail below.
A quick note on terms
In the modern era we tend to use the term 'dependence' to mean a compulsion that on average has no measurable harm, and 'addiction' as a dependence that on average has a clear elevation of risk. So, we call a reliance on coffee, or a compulsion to engage in frequent bird watching, dependence - since no solid evidence has been presented that they are harmful. We term gambling compulsion and heroin use addictions, since on average they involve harm in some form to some degree. However, it could be argued that such terms are a matter of philosophy not medicine, since there is a sizeable cultural element in their definition, and what is normal in one society is abnormal in another; and this may explain why there is no agreed definition of 'addiction' (it takes different forms in different textbooks).
The fact there is no published clinical trial for nicotine dependence in those unexposed to tobacco consumption has to be considered extremely suspicious:
As a result of the multiple clinical trials of nicotine for treating disease; the large-scale tests for nicotine presence in the population; and the enormous data resource on long-term use, we now know that:
To explain point #3: the acute effect (meaning: immediate, short-term, at the time, time-limited) of a large dose of nicotine is to elevate blood sugar, heart rate and blood pressure. These effects are temporary. The chronic effects (meaning: over a period of time, in the long term) are to lower the blood pressure slightly. So we can tell from the easily-seen, simple, mechanical effects that a generous dose of nicotine will enable alertness; and in the long term it reduces blood pressure, which may be a positive for some people and qualify as an improvement in health.
To discuss either the acute or chronic effects in isolation, for some reason, would be inaccurate. For example to state that "nicotine raises the blood pressure" is a particularly effective lie, because it is partly true: it does do this, for a few minutes. In this way, we cannot say the speaker is lying - because in one sense it is true. In the long term, of course, the opposite is true: nicotine tends to lower the blood pressure . The inference of the first statement is that nicotine is unhealthy because it has the chronic effect of raising blood pressure; but this is a lie because the chronic effect is the opposite. So the lie has two levels and a germ of truth; and this is absolutely typical of propaganda issuing from the Public Health industry: it is skilful and cannot be simply dismissed as an outright lie, because it has a grain of truth - but the overall implication is a lie.
From the above, it should be fairly clear that nicotine is commonly misrepresented. The propaganda consists both of outright lies and a subtle twisting of the truth, as shown. In fact such expert use of logical and rhetorical fallacy in argument is typical of the Public Health industry, whose highly expert and extraordinarily wealthy spin doctors are well-paid to produce results. Their results are exceptionally good in terms of public and commercial revenues, so their fees are not wasted. The example above contains clever use of several rhetorical fallacies, which are used to confuse the issue and prevent an accusation of outright lying: the 'failure to quantify', the 'selective choice', the 'misrepresentation of outcomes' fallacies are all used in that example. It is a particularly good example of how lies are used in Public Health.
Overall, the result is a major difference between the medical facts and the public perception of nicotine. When the reasons for this are examined, we find an observable volume of propaganda that continually reinforces incorrect information. This skewing of the facts toward an unrealistic version of reality has a strong revenue-creating (and protecting) value, although much of the propaganda is self-perpetuating and reliant on a form of puritan ideology. An idea of how powerful the propaganda is, and how even medical experts are confused by it, is shown by a recent survey of British and Swedish doctors: 44% of British doctors surveyed reported that they believed nicotine is associated with cancer.
This is directly opposite to their official advice from the national clinical guidance authority, NICE, who have made it very clear that nicotine has no association with cancer. If a doctor gives advice that directly contradicts their official guidance, this would constitute medical negligence (and must undoubtedly have happened given the scale of this issue). So we see that propaganda can result in medical malpractice; and it is not correct to describe this situation as ignorance, as it is carefully stage-managed by a propaganda campaign that has two functions: protect revenues and protect the establishment position (which protects revenues).
In the end it is always about the money, although the footsoldiers are frequently unaware of this. Diligent examination reveals how revenues are created and protected, and how the zealots are controlled from above (as is probably always the case: a zealot by definition has no measure of reality, either in areas of policy, or who is in control of policy, or why they control it). For zealots the goal is a form of religious purity, but it conveniently creates a blind spot in the area of motives and beneficiaries.The sinners must be purified, for their own good, and if the purification is profitable then that is fate and can be accepted with gratitude.
- Nicotine is a normal and natural part of the diet. It is present in many vegetables and some other foodstuffs such as tea.
- In every large-scale clinical study that examined nicotine presence in the population and involved hundreds of people being tested, every person tested positive for nicotine. One test was of 800 people by the CDC in the USA, and all tested positive. (They have done their best to hide this clinical study as it does not agree with their current ideology.) No person has ever tested negative for dietary nicotine in any of these studies.
- A sister compound nicotinic acid is a vitamin, B3. It shares several effects on the human organism with nicotine, and it appears that each has some additional vital functions; for example B3 prevents physical and psychiatric symptoms of nutritional deficiency including pellagra (a serious deformity of the skin).
In some organisms nicotinic acid is a metabolyte of nicotine (but not in humans as far as is known). However, due to the the taboo surrounding it, little research has been carried out into nicotine compared to other dietary ingredients (indeed, the researchers who discovered vitamin B3 had to invent a new name, 'niacin', to disguise the fact they were talking about a nicotine compound).
Nicotinamide, another of the nicotine group of compounds either found in vegetables or created in the organism as a metabolyte, is used for treating skin conditions.
- As a group, the nicotine compounds are clearly associated with brain function and skin health. There are good reasons for believing that these are nutrients, because they clearly have preventive functions against disease and treatment functions in those who present with the conditions these compounds appear to prevent (who may belong to specific genetic groups). Smoking (and it is assumed, nicotine) protects against neurodegenerative and auto-immune disease ; nicotine treats skin disease and some cognitive function disorders.
- There is no evidence that nicotine is addictive. That is to say, the pure form as delivered in the diet (and e-cigarettes).
- What do clinical trials of nicotine dependence tell us? Nothing. There aren't any.
- There is no published clinical trial of nicotine on humans for investigation of dependence. No CT or RCT involving the delivery of pure nicotine to never-smokers to look at dependence issues has ever been published.
- There have been such trials connected with NRTs, but since the subjects were smokers and ex-smokers, dependence on nicotine per se cannot be measured (smoking creates dependence on nicotine - and it is the only route to dependence we know of) .
- None of the multiple trials that examined the benefit of nicotine administration to never-smoker patients suffering from neurodegenerative diseases and similar, which in some cases involved administration of large quantities of pure nicotine to subjects for many months, resulted in any dependence or withdrawal symptoms. It is therefore possible to conclude that, anecdotally, nicotine by itself has no potential for dependence. (These results must be considered as providing anecdotal evidence, since dependence issues were not the main focus of these trials.)
It is possible that repeated delivery of large quantities, in a certain way (e.g. by inhalation, using an effective, high-power device) may cause dependence for a very small number of individuals, since that is possible for many substances; but there is certainly no evidence for it because there is no published clinical trial.
- Note well that all citations on this subject lead to studies of smoking dependence or nicotine dependence in smokers; this is irrelevant since it is delivered along with up to 9,600 other compounds, some of which are likely to be synergens; some are likely to be additives that may boost the effect by freebasing it; some are the multiple other active alkaloids in tobacco; and some pyrolytic compounds may be dependence forming, in addition. Cigarettes are a carefully-engineered product; we might say that cigarettes are 'engineered for brand loyalty'. Another view might be that they are made to be addictive.
- It is probably not difficult to make some compounds dependence-forming if another 9,600 compounds can be added, especially ones specifically designed to boost the dependency potential.
- Scientists who repeat the basic fact that there is no evidence for nicotine (itself) creating dependence are not viewed with favour due to the climate of taboo created by propaganda, the commercial pressures, and the need to protect prior positions especially for senior colleagues; nevertheless, there is no evidence that nicotine is associated with dependence unless delivered in a tobacco vehicle, and especially after repeated delivery in cigarette smoke.
- It is believed that the repeated delivery of tobacco smoke causes a change in brain chemistry that results in dependence. Nicotine becomes associated with dependence after being supplied with a cocktail of 9,600 other compounds . Nicotine is certainly dependence-creating when delivered in cigarette smoke: many (but not all) smokers become dependent on nicotine.
- When research on the addictiveness of nicotine is sought, none can be found; all references point to smoking studies. A typical example is this Wikipedia quote, from the nicotine page: "In many studies it has been shown to be more addictive than cocaine and heroin ". However the first two citations point to NY Times articles, which are not of course published research, and which mention studies (of indeterminate status) on smoking in any case; the third citation is a paper on smoking dependence.
Again, from the Nicotine page: "Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties. However, after coadministration with an MAOI, such as those found in tobacco, nicotine produces significant behavioral sensitization, a measure of addiction potential." 
Leaving aside the desirability of using Wikipedia as a reference; because of the strong presence of the tobacco control industry there it seems highly likely that if citations for the addictive potential of nicotine were available, they ought to be found there. There are none. There are no studies of nicotine dependence in humans. Indeed, even the TCI have not removed (or been able to remove) the statement: "Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties." In fact, of course, it produces none at all when measured in clinical trials.
Indeed, we could probably rephrase that to remove the diffidence exhibited by scientists when they have to carefully step around taboos: "Nicotine has little or no potential for dependence because, taken by itself, it is not demonstrated as having any reinforcing properties".
- Nicotine is not considered any more harmful than coffee, since there is absolutely no evidence for this. Indeed, there is a mountain of evidence that long-term nicotine consumption (without smoke) is close to harmless:
a. The UK clinical guidance authority, NICE, has given strong advice to doctors which clearly indicates that nicotine is not considered harmful , does not cause cancer or heart disease, and is not associated with cancer in any way. This is the official guidance to all UK medical practitioners. Doctors are advised that they can prescribe nicotine in the long term as there is no evidence it causes any harm . This advice is part of the new guidance on smoking harm reduction. 
The RCP opinion is also quoted therein: "The harm associated with cigarette smoking is almost entirely caused by the toxins and carcinogens found in tobacco smoke – not the nicotine (Royal College of Physicians 2007)."
b. Sweden has the lowest smoking-related death rate of any developed country by a wide margin as a result of half or more of smokers using or switching to Snus (Swedish oral tobacco) , the majority of them fairly recently (since 2000). At 2013, 66% of Swedish tobacco users were Snusers and 33% smokers. Snus consumption involves long-term ad lib consumption of nicotine, and a characteristic of Snus is that some products deliver more nicotine than some cigarettes. There are more than 150 clinical studies of Snus over more than 30 years in Sweden. According to Prof PN Lee, the authority on the statistical epidemiology of tobacco consumption, who carried out multiple assessments and large-scale meta-analyses of the Snus studies, Snus consumption cannot be reliably determined to have any elevation of risk for any disease (multiple studies including the following):
c. Prof Rodu confirms Prof Lee's assessment:
d. "Nicotine has about the same implication for health as coffee and fries."
- Dr CV Phillips.
- Multiple senior professors of medicine and public health have affirmed that e-cigarettes are essentially harmless in comparison to tobacco cigarettes:
a. “If all the smokers in Britain stopped smoking cigarettes and started [using] e-cigarettes we would save 5 million deaths in people who are alive today. It’s a massive potential public health prize.”
- Prof John Britton, Chair, Tobacco Advisory Group, Royal College of Physicians.
b. "E-cigarettes are probably about as safe as drinking coffee."
- Prof R West, Director of Tobacco Studies, Department of Epidemiology and Public Health, University College London.
c. "Three months of additional smoking poses a greater risk to someone’s health, on average, than a lifetime of using a low-risk alternative."
- Dr CV Phillips.
d. Electronic cigarettes pose no health concern for users or bystanders.
- Prof I. Burstyn, Drexel USPH.
e. The Cochrane Review of Ecigarettes:
see References - Vaping, Ecigs >> Ecigarettes Research #14.
- There are several clinical studies of animals that appear to show that nicotine administration is associated with morbidity including cancer. It needs to be very clearly pointed out that animal nicotine models do not transfer to humans: the evidence in humans is directly opposite to this and other conclusions drawn from such studies.
- We have a mountain of data on long-term nicotine consumption without smoke in humans, and the volume of this data (along with the facts, such as the national health statistics from Sweden, which are unique; together with the epidemiology demonstrating the reasons behind the facts) shows that nicotine consumption by humans has no demonstrated potential for significant harm. Any harm that can be reliably identified is so far below a level regarded as of clinical significance that it does not exist for clinical purposes and amounts only to uncommon individual cases .
- Consumption of nicotine is not regarded as clinically significant .
- Smoking causes addiction (as harm can be demonstrated) and, frequently, dependence on nicotine. It appears to cause a persistent brain chemistry change. Once the smoking of tobacco is ceased, for the majority of ex-smokers, nicotine dependence remains and then begins to reduce. As long as smoking avoidance is maintained, nicotine dependence reduces; and this also includes those who still consume nicotine: vapers routinely reduce their nicotine consumption over time, with some eventually transiting to zero-nicotine refills. Since vaping is not smoking, it appears that it does not significantly affect the reduction of dependence on nicotine, which seems predominantly related to time since smoking cessation rather than ongoing consumption of nicotine (by vaping or perhaps any other route).
- Nicotine does not create tolerance. Tolerance is normally included in the list of properties of dependence-causing materials or addictive drugs. As is stated above, vapers routinely reduce the amount consumed, for the same effect, as the time to last cigarette smoked recedes into the past. The amount consumed must be reduced, regularly, in order to avoid symptoms of over-consumption. As the effects of smoking recede with time, sensitivity to nicotine increases - even if it is still consumed.
- In contrast, smoking appears to cause tolerance. More cigarettes appear to be needed for the same effect. Conflating smoking with nicotine consumption is an error of ignorance or deliberate misdirection.
- It is inarguable that smokers commonly become dependent on cigarettes, and frequently on nicotine. In contrast, no one has ever shown that nicotine by itself causes even the smallest degree of dependence. Since nothing could be easier to demonstrate, if it were true, it is probably time to stand up to the (public) establishment view and question why something there is no evidence for whatsoever is treated as fact (in public).
In private, of course, there is no such adherence to ridiculous ideology, unfounded myth and commercial pressure: if a researcher wishes to get authorisation to administer very large quantities of nicotine daily (equivalent to 15 cigarettes) to never-smokers, for several months, then they can easily get ethics committee approval. Indeed, some researchers appear to do little else.
It is very clear that ethics committees are perfectly happy to permit such studies and have no reason to prevent them. The only possible reason for such a lack of concern is that no fear of any degree of harm exists: neither from dependence nor toxicity.
- No one has ever shown that nicotine has any association with dependence except when delivered in a tobacco vehicle. Since (1) this would be extremely easy to demonstrate if true, and (2) there are enormous sums of money waiting for the first person able to demonstrate any potential for dependence on nicotine (i.e. pure nicotine, in never-users of tobacco), we can assume it is not possible.
- It is conceivable that the odd case of dependence exists, or could exist if sufficient never-smokers start to take dietary nicotine supplements of sufficient size; but this issue has less to do with nicotine than other factors of a personal nature. It seems highly unlikely that, no matter what circumstances prevail, any clinically significant number of cases will ever be located. When researchers spend a significant portion of their time administering pure nicotine to never-users of tobacco and never see a single case of withdrawal syndrome or dependence, and no clinical trial has ever shown any degree of dependence in never-users of tobacco, we can legitimately question why the phrase 'nicotine addiction' is seen so often in connection with consumer products that have no tobacco in them.
- Of course, nobody mentions 'nicotine addiction' in connection with any pharmaceuticals containing nicotine, because (a) there isn't any, and (b) they don't want to get sued by people with unlimited funds to pursue makers of libellous / slanderous / untrue statements in court. It is strange how nicotine can be clearly and inarguably free of any dependence issues when in a packet with a medical design and a license stamp, and therefore without hindrance given to children as young as 12 without supervision at school, without parental approval; but 'highly addictive' if it is in a packet with a vaping product design. Perhaps the molecule is strongly affected by the packet design?
- Smoking addiction is another matter entirely. No one is arguing about that. Tobacco and tobacco smoke contains 9,600 separate compounds identified to date. It is theoretically possible to create a degree of dependence on carrot juice if you can add any 9,600 compounds of your choice - there are a couple of cases on record, apparently - so if we could boost the power of carrot juice by about 1,000 times then we might get some interesting results. This does not affect the fact that anyone who suggests carrot juice is 'highly addictive' would probably be regarded as mad. We might ask why the same does not apply for nicotine.
In October 2013, toxicologist Prof B Mayer of Graz showed that nicotine is far less toxic than currently claimed, and that the current LD50 of 60mg is up to 20 times too low. His work appears to lay the foundation for an upward adjustment of the LD50 figure to somewhere around 750 - 1,000mg .
It is also worth noting that a potentially fatal dose would need to be administered by a specific or abnormal route, since there are multiple incidents of attempted suicide by ingestion of more than 1,000mg of nicotine, and at least one of 1,500mg, which were survived with no lasting effect at all. Prof Mayer's estimated fatal dose is the dose necessary to be absorbed, which is difficult by ingestion since the vomit reflex expels the material (in adults). As far as is known, there is no case of death by ingestion of nicotine except where the subject was also anaesthetised or had taken anti-emetics to prevent emesis. Thus, a 'nicotine death' must be ascribed instead to mortality caused by a drug cocktail.
Recently, researchers have been looking at paired nicotine systems: delivery of nicotine within a vehicle that has a close connection with normal human activity such as chewing. This has been sparked by reports of several cases of dependence on nicotine chewing gum.
However it looks as if such cases would still be statistically invisible, since the dependence level appears to be way down at the 1 in 200,000 mark or thereabouts.
No doubt more work will be done here because it would be a way to attack vaping, if some sort of dependence potential could be identified, even at these infinitessimally small numbers. Essentially this is in the same ballpark as dependence on carrot juice.
 See the work of Dr P Newhouse, for example.
 A prime example of junk science attacking clean nicotine delivery systems resulted in the researchers being given $3.5 million for more of the same. Propaganda is an extremely well paid profession.
 See this quote from the current world leader in nicotine research (scroll down to quote #1 in the section 'On nicotine's potential for dependence').
 At 2009, research had identified 5,300 compounds in cigarette smoke. By 2013 this was raised to 9,600 (see Refs page).
 NICE repeatedly state that nicotine is not considered significantly harmful, and in addition neither provide any evidence that it may be harmful nor suggest that it may cause harm. By interpretation of the ultra-conservative language used in such circumstances, this indicates that they do not regard it as harmful.
 Apparently NICE claim to have only 5 years' data for NRTs; it is not clear why this is the case when they have been available since 1984. Perhaps they refer to evidence only officially collected in the Uk and only for the recent past. This is interesting as (at 2015) we have 10 years' information on the safety of ecigs, which were first sold in the UK in 2005.
Note also that ecig health issues are far better reported than any issues with pharmaceuticals - we have literally millions of reports to go on, all of which tend to emphasise the tiniest problem encountered; contrast this with a few hundred reports on any pharmaceutical available in the same timeframe, and the fact these reports go through channels that may tend to reduce the impact of such reports or even reduce their availability to public inspection. In contrast, if someone coughs while vaping in Australia, they know about it in Canada three days later, and that information is public property; the value of such intense scrutiny cannot be over-estimated. It seems most unlikely that any other product of any kind is exposed to such intense public examination, due to the 25-million strong (at 2015) global vaping community, their massive online presence, and their refusal to let even the slightest issue pass without comment. If someone's father or someone's cat appear to suffer an ill-effect that might possibly, slightly, remotely be connected with vaping - then doctors in Australia, pulmonologists in Italy and cardiologists in Belgium will be discussing it within the week.
It is absolutely out of the question that any other product of any kind gets this kind of scrutiny.
 Sweden's smoking prevalence is around 11% at Q3 2013. A 'reduction of about half' is dependent on which country it is compared with, and is correct when compared with similar countries such as the UK. A feature of Sweden's prevalence stats is that male smoking prevalence is significantly lower than the female, due to the greater acceptability of Snus to the male population. The male/female smoking prevalence figures are about 8%/15%. The male figure is about 64% less then the equivalent UK figure. The male figure falls at 1% per year and will be only 5% by about 2016. Such figures, like Sweden's mortality and morbidity figures related to smoking, are uniquely low.
 A statistically-confirmable elevation of risk (or other effect) is generally regarded as one that can be identified reliably. In order for this to be the case, it must be larger than 1% because effects smaller than 1% are not regarded as accurate, and therefore are not reliably demonstrated. An effect shown to be of 2% or greater can be described as 'statistically demonstrated', or 'reliably demonstrated' when repeated by multiple different studies.
For an effect to be of clinical significance, it must be large enough to be very reliably demonstrated and also significant to health and to treatment. This size is generally regarded as being 3% or greater. A well-demonstrated 3% or higher elevation of absolute risk is regarded as 'clinically significant'.
It is important to be absolutely clear that this does not apply to nicotine consumption. There has been no study, ever, that demonstrated harm caused by chronic nicotine consumption (obviously: in supra-dietary amounts, by humans). There are two principal data resources for long-term consumption of nicotine without smoke: NRTs, and Swedish Snus. The NRT data resource is miniscule compared to that for Snus, which can be correctly described as a data mountain (which is why it is used by pharmaceutical manufacturers to show there is no demonstrable harm from long-term nicotine consumption, when applying for long-term and dual/multi-use NRT treatment licenses). The Swedish data resource is vast: apart from the facts (always useful) - their unique national health statistics, for example - there are multi-decade studies with nearly 100,000 subjects.
 There is a possibility that there have been clinical trials of NRTs on never-smokers, but it is difficult to find a reference for such a trial. If you can provide a link, we would be grateful. (Please note we are not interested in trials involving smokers or ex-smokers because such trials are obviously irrelevant - nicotine trials are only of any relevance if they are with never-smokers. Actually, never-users of tobacco is a more correct way of phrasing it, since this would also exclude any persons who have become dependent due to ST or snuff use etc.)
 It was first discovered in 1966 by Harold Kahn, a researcher working for the NIH, that non-smokers are 3 times more likely to die from Parkinson's disease than smokers. Later, more than 40 studies are reported to have confirmed this effect. The Director of Research at the Parkinson's Institute said, "There is a huge literature that says smoking protects against Parkinson's".
A similar effect is seen for other neurodegenerative diseases and auto-immune diseases. One auto-immune disease is known as 'the non-smoker's disease' because of this effect.