De Engelse Wikipedia is wel goed onderbouwd met verwijzingen naar onderzoeken. In tegenstelling tot de Nederlandse waarbij duidelijk de effecten van roken en nicotine door elkaar heen gehaald worden.  En schadelijke effecten van roken onterecht aan nicotine worden toegewezen.

Professor Killeen has studied tobacco addiction and one of the questions he asks is this: Why is tobacco addictive, but nicotine not? Killeen said. “What causes the tremendously addicting power of cigarettes is the drug cocktail of nicotine,” he said, not nicotine itself.

Zeer uitgebreide informatie over Nicotine en gezondheid, nicotine gebruik in NRT´s en snus, waarbij alle gezondheidseffecten gevonden in onderzoek op een rijtje gezet wordt.

Dit onderzoek is uitgevoerd door de Central Queensland University, in Australië.  Conclusie : Nicotine-afhankelijkheid vermindert wanneer rokers overstappen naar E-sigaret. Indicatoren van rookverslaving lijken wat betreft consumptie, niet van toepassing op elektrische sigaret gebruik. De redenen om e-sigaretten te gebruiken lijkt minder gedomineerd te worden door het leveren van nicotine.

Nicotine (not smoke) is harmful for the unborn? Science says NO: "had no impairment compared with 65.5% in placebo". Further studies should investigate the clinical effectiveness and safety of higher doses of NRT.

It appears that the dietary intake of nicotine in nonsmokers may be of practical importance in the interpretation of the role of passive smoke inhalation when one is determining nicotine and cotinine levels in body fluids.

In allerlei onderzoeken is het verband tussen roken een hogere bloeddruk gevonden. Hoewel dit eigenlijk alleen opgaat voor stevige rokers van 50 jaar en ouder.  Het ziet er naar uit dat  nicotine daarbij geen rol speelt. Hoewel veel media dat wel beweren.  Zo te zien maken allerlei media hierbij geen onderscheid maken tussen roken en nicotine gebruik. In dit onderzoek is ook gekeken naar mensen die niet rookten maar wel nicotine pleisters gebruiken.  In de conclusie van dit onderzoek staat:
The epidemiologic studies in which blood pressure was recorded when the participants were not smoking have generally shown no significant effect on blood pressure. As a corollary to this, nicotine patches seem to have little adverse effect on the cardiovascular system, and can be safely recommended to patients with hypertension.

vraagtekens bij antirookbeleid voor chronische psychiatrische patiënten. Wegens werking als antidepressiva van nicotine, en van MAOI´s in tabaksrook.

Vapers engaged in compensatory puffing with lower nicotine strength liquid, doubling their consumption. Whilst compensatory puffing was sufficient to reduce craving and withdrawal discomfort, self-titration was incomplete with significantly higher plasma nicotine levels in the high condition.

CONCLUSIONS: Electronic cigarettes that use tank-type atomizers appear to deliver nicotine in more consistent quantities (within the acceptable limits for medicinal nebulizers and similar to the nicotine inhaler) than electronic cigarettes that use cartomizers. The protocol for testing nicotine delivery consistency described in this paper could be effectively used for regulatory purposes.
CONCLUSIE: Elektronische sigaretten die tankatomizers gebruiken, schijnen nicotine in meer consistente hoeveelheden af te geven (binnen de geaccepteerde grenzen voor medische verstuivers en vergelijkbaar met de nicotine inhaler) dan elektronische sigaretten die cartomizers gebruiken."

Conclusie is dat er geen verband is tussen nicotine gebruik en aderverkalking en hart en vaatziekten.
A meta-analysis of adverse events, recorded in the course of 35 trials to evaluate the efficacy of nicotine patches, also failed to document a difference in the rate of acute myocardial infarction between active (n=5501) and placebo (n=3752) treatment groups (Greenland et al., 1998). A more recent meta-analysis (Mills et al., 2010) included 120 studies (92 randomised clinical trials and 28 observational studies) for a total of 177,390 individuals, and found no increased risk for myocardial infarction or death from NRT (for a review on adverse effects and tolerability see also Hays & Ebbert, 2010). The majority of these studies, however, specifically excluded patients with cardiac disease at baseline. A secondary analysis of subjects in the Lung Health Study, a randomized, controlled trial for the prevention of chronic obstructive pulmonary disease, demonstrated that cardiovascular deaths were associated with continuing smoking, but not among those who used nicotine gum for five years. The use or dose of nicotine gum, or concurrent smoking and gum use, was not associated with increased cardiovascular morbidity or mortality (Murray et al., 1996). A case control study of acute myocardial infarction, stroke and death in the UK found no evidence of increased risk in the 56 days after starting NRT for smoking cessation (Hubbard et al., 2005).

Het duurde 2 uur voor nicotine  om door de huid te dringen, en met een gemiddelde snelheid van 4,82 (± 1,05) ug/cm2/uur (microgram per kubieke centimeter van de blootgestelde huid, per uur), of in milligram zijn uitgedrukt tot 0.00482mg/cm2/uur.
Het is onwaarschijnlijk dat blootstellen aan dampvloeistof met 8 mg nicotine per ml kan leiden tot ernstige toxiciteit. Daarnaast zul je normaal gesproken bij morsen op je lichaam dit wegwassen of afvegen.

Public confusion reigns with 9 in 10 believing nicotine is harmful to health

Study on how nicotine might help Alzheimer's

Nonsmoking subjects with amnestic MCI were randomized to transdermal nicotine (15 mg per day or placebo) for 6 months. Nicotine seemed to help cognitive skills with no addictions reported in this trial.

On the University of New Mexico’s North Campus is a building dedicated to trying to cure dementia and Alzheimer's Disease.

The man in charge of tobacco regulation at the Food and Drug Administration says we “need a national debate on nicotine.” Good idea. But first we need to understand what nicotine is – and what it isn’t

Cigarette smoking increases the risk of cardiovascular disease, and smoking cessation significantly reduces the risk within 1-3 years. Therefore, patients with cardiovascular disease should be encouraged to use the most effective therapies available to reach this goal. The use of nicotine replacement therapy (NRT) doubles long-term cessation (Stead et al., 2008). While not all of the efficacy results in trials conducted in patients with cardiac disease show benefit for increased cessation (Joseph & Fu, 2003; Benowitz, 2003; Marsh et al., 2005; Meine et al., 2005), all trials confirm that NRT, even with concurrent smoking, is safe in this population (see Key Finding #11).

Nicotine has no association with cancer. There is no supportable evidence to link nicotine with cancer, and a vast amount of evidence (and irrefutable facts) that there is no such link. The UK national clinical guidance authority, NICE, have made this very clear in their official guidance to doctors.

The results suggest that the inhibition of MAO activity by compounds present in tobacco smoke may combine with nicotine to produce the intense reinforcing properties of cigarette smoking that lead to addiction.
Het is verschillende mensen die stopten met roken met nicotine hulpmiddelen als e-sigaret of nicotine kauwgum, dat juist niet de nicotine alleen verslavend werkt. Ook niet-rokers die nicotine tijdens onderzoeken nicotine gebruikten voor langere tijd ondervonden geen verslavingsverschijnselen.  Dit onderzoek ondersteunt dergelijke ervaringen. Er zijn andere stoffen nodig om tabaksrook verslavend te maken. Daarbij komen MAOI´s  erg in aanmerking voor de verslavende werking van tabaksrook. Ook dit onderzoek bevestigd de grote invloed van MAOI´s.

Anyone thinking nicotine is addictive needs to read this. It patently isn't.

The  clinical  trial  and  observational  data  indicate  that,  in relation to cardiovascular outcomes, NRT is safe and specifically does not increase the  incidence  of  acute  cardiovascular  events  or  of  sudden  death  in  healthy  volunteers, the general population or patients with pre-existing cardiovascular disease.
Dit komt er op neer dat uit allerlei soorten onderzoek blijkt dat NRT (nicotine therapie als hulpmiddel bij stoppen met roken) veilig is, en dat zowel bij gezonde bevolking als bij patiënten met reeds bestaande hart- en vaatziekten, er geen toename is van hartziekten of plotselinge dood.

Standard textbooks, databases, and safety sheets consistently state that the lethal dose for adults is 60 mg or less (30–60 mg), leading to safety warnings that ingestion of five cigarettes or 10 ml of a dilute nicotine-containing solution could kill an adult. The 60-mg dose would correspond to an oral LD50 of around 0.8 mg/kg, a dose that is considerably smaller than the values determined for laboratory animals, which are ranging from 3.3 (mice) to more than 50 mg/kg (rats) (Hayes 1982).
Although an LD50 of 0.8 mg/kg would implicate that the toxicity of nicotine is similar to or even higher than that of cyanide, fatal nicotine intoxications are relatively rare, and there are countless records of subjects who survived consumption of nicotine in amounts far higher than 60 mg (Larson et al. 1961). The most drastic example is probably survival of a suicide attempt with 4 g of pure nicotine. Ingestion of tobacco or nicotine gums at doses up to 6 mg/kg nicotine was reported to evoke symptoms of intoxication without causing death . These and many other literature reports on nonfatal nicotine intoxications are hardly compatible with a lethal dose of 60 mg or less.

Researchers at Onassis Cardiac Surgery Center evaluated the effects of electronic cigarette use on the maximal ability of the coronary arteries to supply with blood and oxygen the heart itself. They recruited 60 participants, 30 smokers and 30 electronic cigarette users. Measurement of maximal coronary blood flow was performed in smokers before and after smoking 2 cigarettes and, on a separate day, after using an electronic cigarette with 18mg/ml nicotine concentration for 15 minutes. In electronic cigarette users, coronary circulation was evaluated before and after using the same electronic cigarette device for 15 minutes.
After smoking 2 cigarettes, the researchers observed a 16% reduction in maximal coronary blood flow and a 19% elevation in resistance to flow. However, after electronic cigarette use, no difference in coronary blood flow and resistance was observed compared to the baseline measurement. “The results are impressive and indicate that, unlike tobacco, electronic cigarette use does not affect the oxygenation of the heart”

Samengevat komt het er op neer dat die stijfheid een tijdelijk effect is, en dat zelfde effect ontstaat na een kop koffie drinken en veel andere dingen  die we doen zoals het kijken naar een spannende film. En heeft geen schadelijke gevolgen op de lange termijn.
Blood vessels need to be elastic in order to properly deliver blood from the heart to the vital organs. It is well-known that one of the main adverse effects of smoking is acute stiffening of the blood vessels.
Researchers from Onassis Cardiac Surgery Center in Greece recruited 108 healthy subjects (51 smokers and 57 electronic cigarette users). All participants were evaluated at baseline, after smoking and vaping abstinence for 8 hours. Smokers were asked to smoke 2 tobacco cigarettes and use an 18mg/ml nicotine-containing electronic cigarette for 10 minutes on 2 separate days; electronic cigarette users were evaluated after 10 minutes of electronic cigarette use. Subjects were evaluated 20 minutes after use, by echocardiographic measurement of 3 elasticity parameters of the aorta.
Smoking 2 tobacco cigarettes caused significant stiffening of the aorta; all measured parameters showed a 17-22% worsening of elastic properties. On the contrary, both in smokers and electronic cigarette users, no difference was observed after electronic cigarette use. The results are important because aortic elasticity is a significant predictor of future cardiovascular events.
Watching a suspense movie also increases aortic stiffness, but no one would argue that watching a movie has cardiovascular effects that are "as bad as smoking, https://www.ncbi.nlm.nih.gov/pubmed/19251872

Bij rokers blijkt de overstap Nicotine-arme sigaretten over langere tijd niet als effect te hebben, dat rokers minder tabaksigaretten gaan  roken.  Dit is geen geschikte idee om mensen te laten stoppen met roken.  Omdat de gebruikers echte sigaretten blijft gebruiken, krijgt de gebruiker nog steeds alle ongezonde en kankerverwekkende stoffen binnen. Er is dus geen reden om over te stappen op nicotine-arme sigaretten.
Long term study indicates reduced nicotine t0bacco used in cigarettes does not  reduces smoking.

Infants born to women who used NRT for smoking cessation in pregnancy were more likely to have unimpaired development.
Baby's van vrouwen die NRT (nicotine pleisters) gebruikt voor het stoppen met roken tijdens de zwangerschap hadden meer kans om ongeschonden ontwikkeling van hun baby. Deze vrouwen werden vergeleken met een groep die gestopt waren met roken en een placebo kregen en persoonlijke begeleiding.  Opmerkelijk is dus hierbij dat nicotine pleisters gebruiken dus een positieve invloed had, vergeleken bij geen nicotine gebruiken.

As Professor Karl Fagerström explains in Dependence on tobacco and nicotine, it isn’t as simple as a single substance addiction. It’s rather complex with lots of individual differences.

We used to believe that nicotine is very dependence producing, but the evidence suggests that there are a number of problems with this statement. For example, animals do not self-administer nicotine as readily as they do other dependence producing drug. Abstinent smokers seem to prefer a much reduced or nicotine free e-cigarette rather than other - often stronger - nicotine-containing products like gum; and although nicotine replacement treatment is an effective aid for quitting smoking, its efficacy is moderate even in doses that replace most or all nicotine from the cigarettes formerly used (Dale et al. 1995). There is very little to no evidence for the abuse of nicotine when not delivered in a tobacco vehicle.

Cigarette smoking increases blood coagulability, a major risk factor for acute cardiovascular events, whereas transdermal nicotine does not appear to do so. Clinical trials of NRT in patients with underlying, stable coronary disease suggest that nicotine does not increase cardiovascular risk. The risks of NRT for smokers, even for those with underlying cardiovascular disease, are small and are substantially outweighed by the potential benefits of smoking cessation.

Interessant artikel van psychiater Anna Fels (psychiatrist at Weill Cornell Medical College).  Buiten dat het boeiend is over wat nicotine kan betekenen voor een mens, is ook het volgende wat zij zegt van belang:
I called several experts in the field and they all agreed that there are no well-documented serious harmful effects of non-tobacco nicotine products — other than addiction. 
Kort gezegd, nicotine is niet gevaarlijk en veroorzaakt geen ziekten. Het kan verslavend zijn. En in een sigaret is het probleem dat je daarmee kankerverwekkende en andere ziekmakende stoffen binnen krijgt.

Derivatives of nicotine such as cotinine have great potential to become effective agents to prevent and alleviate neurological symptoms developed in subjects with Parkinsonism. It is surprising the absence of funding for the clinical development of these compounds, as they could be therapeutic solutions which have been lying in front of our eyes for hundreds of years, waiting for development.

Het potentieel verslavende stofje pyrazine wordt ook aan tabak toegevoegd. Naast pakweg een stuk of 8 andere verslavende stoffen als  MAOI´s en nicotine en een aantal op nicotine lijkende stoffen.

Adding a nicotine patch (15 mg per 16 hours) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes.
Het geven van een nicotinepleister (15 mg per 16 uur) aan vrouwen die rookten tijdens de zwangerschap, liet niet meer vrouwen stoppen met roken. Maar gaf ook geen extra risico op bijwerkingen of nadelige effecten bij de zwangerschap of geboorte, bij vrouwen die dit gebruikten.

The addictiveness of nicotine is a white male construc.

=>Dit onderzoek laat zien dat mannen die niet roken maar wel tabak in de vorm van snus gebruiken aanzienlijk lager risico lopen op de ziekte van Parkinson.  De resultaten toonden ook een omgekeerde dosis-respons relatie tussen snus gebruik en het risico op de ziekte van Parkinson. Deze resultaten impliceren dat nicotine of andere bestanddelen van tabaksbladeren de ontwikkeling van de ziekte van Parkinson kunnen beïnvloeden.
=>Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease.

Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums, which themselves are not very addictive. (komt overeen met onderzoeken dat nicotine alleen hoog verslavend is in tabak, dus in combinatie met andere stoffen die in tabak toegevoegd worden).

Studie van Jean-François Etter. Institute of Global Health, University of Geneva.
Conclusies:  Sommige e-sigaret gebruikers zijn afhankelijk van nicotine-bevattende e-sigaretten. Maar E-sigaretten waren minder verslavend dan tabak sigaretten. E-sigaretten kunnen minder verslavend zijn als nicotine kauwgum, en die kauwgum zelf is ook niet er verslavend.

CONCLUSIONS: Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums, which themselves are not very addictive.
Conclusies: Sommige e-sigaret gebruikers zijn afhankelijk van nicotine-bevattende e-sigaretten. Maar  e-sigaretten waren minder verslavend dan tabak sigaretten. E-sigaretten is  minder verslavend als nicotine kauwgum, wat van zichzelf niet erg verslavend is.

A wide range of electronic cigarette (EC) devices, from small cigarette-like (first-generation) to new-generation high-capacity batteries with electronic circuits that provide high energy to a refillable atomizer, are available for smokers to substitute smoking. Nicotine delivery to the bloodstream is important in determining the addictiveness of ECs, but also their efficacy as smoking substitutes. In this study, plasma nicotine levels were measured in experienced users using a first- vs. new-generation EC device for 1 hour with an 18 mg/ml nicotine-containing liquid.
==> Plasma nicotine levels were higher by 35–72% when using the new- compared to the first-generation device.
==>Compared to smoking one tobacco cigarette, the EC devices and liquid used in this study delivered one-third to one-fourth the amount of nicotine after 5 minutes of use.
==>New-generation EC devices were more efficient in nicotine delivery, but still delivered nicotine much slower compared to tobacco cigarettes.
==>The use of 18 mg/ml nicotine-concentration liquid probably compromises ECs' effectiveness as smoking substitutes; this study supports the need for higher levels of nicotine-containing liquids (approximately 50 mg/ml) in order to deliver nicotine more effectively and approach the nicotine-delivery profile of tobacco cigarettes.

Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century

Nicotine bereikt na 7 seconden de hersenen. In een onderzoek kregen de deelnemers sigaretten zonder en met nicotine te roken. Zij moesten snel, binnen 7 seconden aangeven welke sigaret zij het meest waardeerde. Daarbij bleken sigaretten met nicotine de voorkeur te hebben. De prikkelende sensaties in de luchtwegen werden gemist in sigaretten zonder nicotine.
Dit feit ondersteunt dat niet de nicotine verslaving niet vergelijkbaar is met ontwenningsverschijnselen die ontstaan bij bijvoorbeeld een heroïne verslaving.
=>  Dit is herkenbaar bij een aantal e-sigaret gebruikers die een tijd zonder nicotine gedampt hebben. Zij hebben niet de trek naar nicotine maar voegen een hele kleine hoeveelheid toe. Zij dampen vaak 1mg per ml voor de smaak beleving. (dergelijke kleine hoeveelheden zijn niet eens te koop, maar kunnen ze doen door dampvloestof met weinig en zonder nicotine te mengen).
=>Er zijn een groot aantal aanwijzingen dat juist nicotine in combinate met een 12 tal andere stoffen in tabaksrook erg verslavend is. Maar juist niciotine alleen, b.v. aangeleverd in nicotine pleisters of e-sigaretten, juist veel minder verslavend is. Ook bij onderzoek met dieren blijkt het vrijwel onmogelijk dieren verslaafd te maken aan nicotine.

It has never been proven that nicotine exposure is a carcinogen in humans. More so, the FDA has strongly proclaimed nicotine as safe for long-term use and eliminated the required time limit recommendations on labeling for over-the-counter nicotine products. The most recent research still hasn’t shown a link between nicotine products and cancer, either.
Onderzoek:
In the adjusted models for lung cancer, nicotine replacement therapy alone was not a significant predictor (p = .57), while smoking during the Lung Health Study was a significant predictor (p = .03). When nicotine replacement therapy and smoking were entered in the same model, nicotine replacement therapy remained not significant (p = .25) and smoking was clearly significant (p = .02). Nicotine replacement therapy and smoking were not significant predictors of cancer in the models for gastrointestinal cancer or all cancers.

Non-nicotine tobacco products can play a significant role in enhancing the reinforcing effects of nicotine. Addition of acetaldehyde to nicotine facilitates initial acquisition of nicotine self-administration in adolescent rats (Belluzzi et al. 2005), whereas treatment with MAOIs significantly increases self-administration and prolongs the aversive state of nicotine withdrawal (Guillem et al. 2005, 2008). In the present study, we have shown for the first time that a cocktail of the minor tobacco alkaloids: anabasine, anatabine, cotinine, myosmine and nornicotine produces a similar effect. At concentrations relevant to those contained in cigarette smoke, addition of the minor alkaloids to the nicotine infusion solution significantly enhanced locomotor activity and sensitization, increased the reinforcing efficacy of nicotine over several doses and strengthened rats' motivation to obtain nicotine. We have also shown that of the minor alkaloids tested, myosmine, anatabine and cotinine individually increased nicotine-induced locomotor activity, highlighting a possible role for these specific minor alkaloids in tobacco addiction.

The Lung Health Study enrolled 5,887 participants in a randomized trial to prevent chronic obstructive pulmonary disease. The present study used surveillance data on 3,320 intervention participants who enrolled in the Lung Health Study for 5 years and who were then followed by the Lung Cancer Substudy for 7.5 years.  ===>Although the surveillance time was short, smoking predicted cancer in this analysis and nicotine replacement therapy did not.

Research: Nicotine is the major neuroactive compound of tobacco, but according to this 2005 paper; on its own it has weak reinforcing (addictive) properties. It appears other compounds found in tobacco smoke when combined with nicotine  produce the intense reinforcing properties of cigarette smoking that lead to addiction."

Rats breathed in a chamber with nicotine at a concentration giving twice the plasma concentration found in heavy smokers. Nicotine was given for 20 h a day, five days a week during a two-year period. Conclusion: our study does not indicate any harmful effect of nicotine when given in its pure form by inhalation. Particularly, there was no microscopic or macroscopic lung tumors nor any increase in pulmonary neuroendocrine cells.