Electronic cigarette

Estimated trends in the global number of vapers

E-cigarette use rose exponentially.[12][41][42] In 2011 there were about 7 million adult e-cigarette users globally, rising to 41 million in 2018 [43] and to 68 million in 2020 compared with 1.1 billion cigarette smokers.[44]

E-cigarette use is highest in China, the US, and Europe, with China having the most e-cigarette users.[5][45] In the UK, growth was slowing as of January 2018.[46] The rise was thought to be due to advertising to young people; their low cost compared to tobacco; and the perception that e-cigarettes are safer than tobacco.[47]

US

In 2018, current (30 day) e-cigarette use was about 20% in American high school students and about 3% in adults.[48]

UK

In the UK, users increased from 700,000 in 2012 to 2.6 million in 2015.[49] About 60% of UK users are smokers and about 40% are ex-smokers, while use among never-smokers in the UK is negligible.[49]

Australia

According to a 2019 report, approximately 520,000 of adult Australians were vaping. That was more than twice as much as in a 2016 survey where only 240,000 of Australians were vapers.[50]

Many users begin with a disposable e-cigarette resembling a tobacco cigarette.[51][52] They often progress to later-generation devices[52] and may adjust their devices to provide more vapor.[53] Experienced users often prefer rechargeable e-cigarettes.[54] Women prefer disposable e-cigarettes, and young adults pay more attention to modifiability.[54] Modifiability increases the chance of starting vaping among young people.[54]

Most vapers use a refillable tank system, allowing them to mix their own liquid giving control over flavor and strength.[54][55] Experienced vapers rank customizability as the most important consideration in choosing a device.[54] Users ranked nicotine strength as an important factor for choosing among various e-cigarettes, though such preference could vary by smoking status, e-cigarette use history, and gender.[54] Non-smokers and inexperienced e-cigarettes users tended to prefer no nicotine or low nicotine e-cigarettes while smokers and experienced e-cigarettes users preferred medium and high nicotine e-cigarettes.[54]

Today, more high school students use e-cigarettes than regular cigarettes.[56] A higher proportion of high school students vape than adults do, and vaping by young people rose 900% between 2011 and 2015.[56]

Worldwide, increasing numbers of young people are vaping; more in some countries than others.[57][58] With access to e-cigarettes, young people have been using tobacco about a quarter as often.[59][60][61][62] Vaping among adolescents grew every year until 2017.[63] There appears to be an increase of one-time e-cigarette use among young people worldwide.[64]

Most young e-cigarette users have never smoked,[65] but there is a substantial minority who both vape and smoke, which indicates that e-cigarettes may be a starting point for nicotine use.[10] Young people who would not smoke are vaping,[66][67] and young people who vape are more likely to start smoking.[68][69][70] Twice as many young people vaped in 2014 than also used traditional cigarettes.[71] Young people who smoke tobacco or marijuana, or who drink alcohol, are much more likely to vape.[72][73] Among young people who have tried vaping, most used a flavored product the first time.[72][54]

Most young people are not vaping to help them quit tobacco.[74][11] Vaping correlates with smoking among young people, even in those who would otherwise be unlikely to smoke.[75] Experimenting with vaping encourages young people to continue smoking.[76] A 2015 study found minors had little resistance to buying e-cigarettes online.[77] Teenagers may not admit using e-cigarettes, but use, for instance, a hookah pen.[78] As a result, self-reporting may be lower in surveys.[78]

There are varied reasons for e-cigarette use.[5] Most users are trying to quit smoking,[79] but a large proportion of use is recreational[5][6] or as a way to get around smoke-free laws.[67][79] Most still smoke, raising concern that dual use may "delay or deter quitting".[10] Some people say they want to quit smoking by vaping, but others vape to circumvent smoke-free laws and policies, or to cut back on cigarette smoking.[10][80][81] Many vape because they believe vaping is safer than smoking.[82][83] [84]

Concerns over avoiding stains on teeth or odor from smoke on clothes in some cases prompted interest in or use of e-cigarettes.[6] Some e-cigarettes appeal considerably to people curious in technology who want to customize their devices.[85] There appears to be a hereditary component to tobacco use, which probably plays a part in transitioning of e-cigarette use from experimentation to routine use.[4]

Reasons for initiating e-cigarette use in the European Union according to a Eurobarometer poll (2018).[86]

Users say they like the choice of flavors and comparatively low price.[87][6]

In the context of drugs, the gateway hypothesis is that using less harmful drugs can lead to a future risk of using more harmful drugs or crime.[88] Some research suggests vaping is a "gateway" to smoking.[89][90] However, it is also plausible that any favorable relation between vaping and starting smoking is a result of common risk factors.[91][92] [93] Research that controls for confounding factors generally finds that vaping is an "exit ramp" from smoking.[94][95] In other words, e-cigarettes are displacing cigarettes.[96][97]

A 2020 report of 25 studies and three systematic reviews found that every study examined found e-cigarette use increased odds of later smoking.[98]

Because those with mental illness are highly predisposed to nicotine addiction, those who try e-cigarettes may be more likely to become dependent, raising concerns about facilitating a transition to combustible tobacco use.[87] Even if an e-cigarette contains no nicotine, the user mimics the actions of smoking.[99] This may renormalize tobacco use in the general public.[99][100] There is a possible risk of re-normalizing of tobacco use in areas where smoking is banned.[99] Government intervention is recommended to keep children safe from the re-normalizing of tobacco, according to a 2017 review.[63]

The "catalyst model" suggests that vaping may proliferate smoking in minors by sensitizing minors to nicotine with the use of a type of nicotine that is more pleasing and without the negative attributes of regular cigarettes.[101] A 2016 review, based on the catalyst model, "indicate that the perceived health risks, specific product characteristics (such as taste, price and inconspicuous use), and higher levels of acceptance among peers and others potentially make e-cigarettes initially more attractive to adolescents than tobacco cigarettes. Later, increasing familiarity with nicotine could lead to the reevaluation of both electronic and tobacco cigarettes and subsequently to a potential transition to tobacco smoking."[57]

The Royal College of Midwives states, "While vaping devices such as electronic cigarettes (e-cigs) do contain some toxins, they are at far lower levels than found in tobacco smoke. If a pregnant woman who has been smoking chooses to use an e-cig and it helps her to quit smoking and stay smokefree, she should be supported to do so." Based on the available evidence on e-cigarette safety, there was also "no reason to believe that use of an e-cig has any adverse effect on breastfeeding." The statement went on to say, "vaping should continue, if it is helpful to quitting smoking and staying smokefree". The UK National Health Service says: "If using an e-cigarette helps you to stop smoking, it is much safer for you and your baby than continuing to smoke.".[119] Many women who vape continue to do so during pregnancy because of the perceived safety of e-cigarettes compared to tobacco.[81]

In one of the few studies identified, a 2015 survey of 316 pregnant women in a Maryland clinic found that the majority had heard of e-cigarettes, 13% had used them, and 0.6% were current daily users.[72] These findings are of concern because the dose of nicotine delivered by e-cigarettes can be as high or higher than that delivered by traditional cigarettes.[72]

Data from two states in the Pregnancy Risk Assessment System (PRAMS) show that in 2015—roughly the mid-point of the study period—10.8% of the sample used e-cigarettes in the three months prior to the pregnancy while 7.0%, 5.8%, and 1.4% used these products at the time of the pregnancy, in the first trimester, and at birth respectively.[120] According to National Health Interview Survey (NHIS) data from 2014 to 2017, 38.9% of pregnant smokers used e-cigarettes compared to only 13.5% of non-pregnant, reproductive age women smokers.[121] A health economic study found that passing an e-cigarette minimum legal sale age law in the United States increased teenage prenatal smoking by 0.6 percentage points and had no effect on birth outcomes.[122] Nevertheless, additional research needs to be done on the health effects of electronic cigarette use during pregnancy.[123][124]

Effects of vaping, compared to tobacco smoking.[125]

The term harm reduction implies any reduction in relative harm from a prior level, even a small reduction such as reducing smoking by one or two cigarettes per day.[126] Harm minimization strives to reduce harms to zero (i.e., ideally to no use and thus no harmful exposure).[126] When a consumer does not want to stop all nicotine use, then harm minimization implies striving for the complete elimination of smoked tobacco exposure by substituting it with the use of less harmful noncombusted forms of nicotine instead of smoking.[126] Tobacco harm reduction (THR) may serve as a substitute for traditional cigarettes with lower risk products to reduce tobacco-related death and disease.[127] Tobacco harm reduction has been a controversial area of tobacco control.[108] Health advocates have been slow to support a harm reduction method out of concern that tobacco companies cannot be trusted to sell products that will lower the risks associated with tobacco use.[108] E-cigarettes can reduce smokers' exposure to carcinogens and other toxic chemicals found in tobacco.[4] A large number of smokers want to reduce harm from smoking by using e-cigarettes.[128] The argument for harm reduction does not take into account the adverse effects of nicotine.[42] There cannot be a defensible reason for harm reduction in children who are vaping with a base of nicotine.[129] Quitting smoking is the most effective strategy to tobacco harm reduction.[130]

Tobacco smoke contains 100 known carcinogens, and 900 potentially cancer causing chemicals, but e-cigarette vapor contains less of the potential carcinogens than found in tobacco smoke.[31] A study in 2015 using a third-generation device found levels of formaldehyde were greater than with cigarette smoke when adjusted to a maximum power setting.[33] E-cigarettes cannot be considered safe because there is no safe level for carcinogens.[108] Due to their similarity to traditional cigarettes, e-cigarettes could play a valuable role in tobacco harm reduction.[131] However, the public health community remains divided concerning the appropriateness of endorsing a device whose safety and efficacy for smoking cessation remain unclear.[131] Overall, the available evidence supports the cautionary implementation of harm reduction interventions aimed at promoting e-cigarettes as attractive and competitive alternatives to cigarette smoking, while taking measures to protect vulnerable groups and individuals.[131]

The core concern is that smokers who could have quit entirely will develop an alternative nicotine addiction.[108] Dual use may be an increased risk to a smoker who continues to use even a minimal amount of traditional cigarettes, rather than quitting.[10] The promotion of vaping as a harm reduction aid is premature,[107] while a 2011 review found they appear to have the potential to lower tobacco-related death and disease.[108] Evidence to substantiate the potential of vaping to lower tobacco-related death and disease is unknown.[132] The health benefits of reducing cigarette use while vaping is unclear.[133] E-cigarettes could have an influential role in tobacco harm reduction.[131] The authors warned against the potential harm of excessive regulation and advised health professionals to consider advising smokers who are reluctant to quit by other methods to switch to e-cigarettes as a safer alternative to smoking.[9] A 2014 review recommended that regulations for e-cigarettes could be similar to those for dietary supplements or cosmetic products to not limit their potential for harm reduction.[127] A 2012 review found e-cigarettes could considerably reduce traditional cigarettes use and they likely could be used as a lower risk replacement for traditional cigarettes, but there is not enough data on their safety and efficacy to draw definite conclusions.[134] There is no research available on vaping for reducing harm in high-risk groups such as people with mental disorders.[135]

A 2014 PHE report concluded that hazards associated with products currently on the market are probably low, and apparently much lower than smoking.[128] However, harms could be reduced further through reasonable product standards.[128] The British Medical Association encourages health professionals to recommend conventional nicotine replacement therapies, but for patients unwilling to use or continue using such methods, health professionals may present e-cigarettes as a lower-risk option than tobacco smoking.[136] The American Association of Public Health Physicians (AAPHP) suggests those who are unwilling to quit tobacco smoking or unable to quit with medical advice and pharmaceutical methods should consider other nicotine containing products such as e-cigarettes and smokeless tobacco for long-term use instead of smoking.[137] A 2014 WHO report concluded that some smokers will switch completely to e-cigarettes from traditional tobacco but a "sizeable" number will use both.[89] This report found that such "dual use" of e-cigarettes and tobacco "will have much smaller beneficial effects on overall survival compared with quitting smoking completely."[89]

As of 2014, the available research on the efficacy of e-cigarette use for smoking cessation was limited.[90] Data regarding their use includes four randomized controlled trials[138] and a number of user surveys, case reports, and cohort studies.[139] There is tentative evidence they may help people quit smoking.[106] Vaping does not greatly increase the odds of quitting smoking.[140] Their use for quitting smoking is controversial.[141] As a result of the data being confronted with methodological and study design limitations, no firm conclusions can be drawn in respect to their efficacy and safety.[142] A 2016 review found that the combined abstinence rate among smokers using e-cigarettes in prospective studies was 29.1%.[141] The same review noted that few clinical trials and prospective studies had yet been conducted on their effectiveness, and only one randomized clinical trial had included a group using other quit smoking methods.[141] No long-term trials have been conducted for their use as a smoking cessation aid.[143] It is still not evident as to whether vaping can adequately assist with quitting smoking at the population level.[144] A 2015 PHE report recommends for smokers who cannot or do not want to quit to use e-cigarettes as one of the main steps to lower smoking-related disease,[145] while a 2015 US PSTF statement found there is not enough evidence to recommend e-cigarettes for quitting smoking in adults, pregnant women, and adolescents.[79] In 2021 the US PSTF concluded the evidence is still insufficient to recommend e-cigarettes for quitting smoking, finding that the balance of benefits and harms cannot be determined. [146] As of January 2018, systematic reviews collectively agreed that there is insufficient evidence to unequivocally determine whether vaping helped people abstain from smoking.[147] A 2020 systematic review and meta-analysis of 64 studies found that on the whole as consumer products e-cigarettes do not increase quitting smoking.[148]

Studies pertaining to their potential impact on smoking reduction are very limited.[149] E-cigarette use may decrease the number of cigarettes smoked,[150] but smoking just one to four cigarettes daily greatly increases the risk of cardiovascular disease compared to not smoking.[10] The extent to which decreasing cigarette smoking with vaping leads to quitting is unknown.[151] Randomized controlled trials have not shown that vaping is effective for quitting smoking.[138] A 2016 meta-analysis based on 20 different studies found that smokers who used e-cigarettes were 28% less likely to quit than those who had not tried e-cigarettes.[152] This finding persisted whether the smokers were initially interested in quitting or not.[152] Tentative evidence indicates that health warnings on vaping products may influence users to give up vaping.[153]

It is unclear whether e-cigarettes are only helpful for particular types of smokers.[154] Vaping with nicotine may reduce tobacco use among daily smokers.[155] Whether or not vaping is potentially effective for quitting smoking may rely upon whether it was used as part of making an effort to quit or not.[149]

Vaping is not clearly more or less effective than regulated nicotine replacement products or 'usual care' for quitting smoking.[138] The available research suggests e-cigarettes are likely equal or slightly better than nicotine patches for quitting smoking.[19] People who vaped were not more likely to give up smoking than people who did not vape.[156] Compared to many alternative quitting smoking medicines in early development in clinical trials including e-cigarettes, cytisine appears to be most encouraging in efficacy and safety with an inexpensive price.[157] E-cigarettes have not been proven to be more effective than smoking cessation medicine[16] and regulated US FDA medicine.[102][11] A 2014 review found they may be as effective, but not more, compared to nicotine patches for short-term quitting smoking.[74] They also found that a randomized trial stated 29% of e-cigarette users were still vaping at 6 months, while only 8% of patch users still wore patches at 6 months.[74] Some individuals who quit smoking with a vaping device are continuing to vape after a year.[158] Vaping appears to be as effective as nicotine replacement products, though its potential adverse effects such as normalizing smoking have not been adequately studied.[159] While some surveys reported improved quitting smoking, particularly with intensive e-cigarette users, several studies showed a decline in quitting smoking in dual users.[3] A 2015 overview of systematic reviews indicates that e-cigarettes has no benefit for smokers trying to quit, and that the high rate of dual use indicates that e-cigarettes are used for supporting their nicotine addiction.[160] Other kinds of nicotine replacement products are usually covered by health systems, but because e-cigarettes are not medically licensed they are not covered.[158]

It is difficult to reach a general conclusion from e-cigarette use for smoking cessation because there are hundreds of brands and models of e-cigarettes sold that vary in the composition of the liquid.[106] E-cigarettes have not been subjected to the same type of efficacy testing as nicotine replacement products.[161] The similarity of e-cigarettes' vapor, looking like cigarette smoke, may prolong traditional cigarette use for people who could have quit instead, but the growing support of e-cigarettes could put extra pressure on smokers to stop cigarette smoking because smoking may be seen as socially unacceptable compared to a smokeless e-cigarette.[131] The evidence indicates smokers are more frequently able to completely quit smoking using tank devices compared to cigalikes, which may be due to their more efficient nicotine delivery.[103] There is low quality evidence that vaping assists smokers to quit smoking in the long-term compared with nicotine-free vaping.[103] Nicotine-containing e-cigarettes were associated with greater effectiveness for quitting smoking than e-cigarettes without nicotine.[162] A 2013 study in smokers who were not trying to quit, found that vaping, with or without nicotine decreased the number of cigarettes consumed.[163] E-cigarettes without nicotine may reduce tobacco cravings because of the smoking-related physical stimuli.[108] A 2015 meta-analysis on clinical trials found that e-cigarettes containing nicotine are more effective than nicotine-free ones for quitting smoking.[162] They compared their finding that nicotine-containing e-cigarettes helped 20% of people quit with the results from other studies that found nicotine replacement products helps 10% of people quit.[162] A 2016 review found low quality evidence of a trend towards benefit of e-cigarettes with nicotine for smoking cessation.[142] In terms of whether flavored e-cigarettes assisted quitting smoking, the evidence is inconclusive.[54]

As of 2020, the efficacy and safety of vaping for quitting smoking during pregnancy was unknown.[164] No research is available to provide details on the efficacy of vaping for quitting smoking during pregnancy.[132] There is robust evidence that vaping is not effective for quitting smoking among adolescents.[75] In view of the shortage of evidence, vaping is not recommend for cancer patients.[165] The effectiveness of vaping for quitting smoking among vulnerable groups is uncertain.[166]

As of 2015, research had not yet provided a consensus on the risks of e-cigarette use.[11][79][102] There is little data about their safety, and a considerable variety of liquids are used as carriers,[160] and thus are present in the aerosol delivered to the user.[10] Reviews of the safety of e-cigarettes have reached quite different conclusions.[167] A 2014 WHO report cautioned about potential risks of using e-cigarettes.[168] Regulated US FDA products such as nicotine inhalers may be safer than e-cigarettes,[107] but e-cigarettes are generally seen as safer than combusted tobacco products[76][110] such as cigarettes and cigars.[76] The risk of early death is anticipated to be similar to that of smokeless tobacco.[104] Since vapor does not contain tobacco and does not involve combustion, users may avoid several harmful constituents usually found in tobacco smoke,[169] such as ash, tar, and carbon monoxide.[170] However, e-cigarette use with or without nicotine cannot be considered risk-free[171] because the long-term effects of e-cigarette use are unknown.[103][104][105]

Possible side effects of nicotine[172]

The cytotoxicity of e-liquids varies,[173] and contamination with various chemicals have been detected in the liquid.[29] Metal parts of e-cigarettes in contact with the e-liquid can contaminate it with metal particles.[169] Many chemicals including carbonyl compounds such as formaldehyde can inadvertently be produced when the nichrome wire (heating element) that touches the e-liquid is heated and chemically reacted with the liquid.[174] Normal usage of e-cigarettes,[33] and reduced voltage (3.0 V[2]) devices generate very low levels of formaldehyde.[174] The later-generation and "tank-style" e-cigarettes with a higher voltage (5.0 V[173]) may generate equal or higher levels of formaldehyde compared to smoking.[3] A 2015 PHE report found that high levels of formaldehyde only occurred in overheated "dry-puffing".[175] Users detect the "dry puff" (also known as a "dry hit"[176]) and avoid it, and they concluded that "There is no indication that EC users are exposed to dangerous levels of aldehydes."[175] However, e-cigarette users may "learn" to overcome the unpleasant taste due to elevated aldehyde formation, when the nicotine craving is high enough.[177] E-cigarette users who use devices that contain nicotine are exposed to its potentially harmful effects.[2] Nicotine is associated with cardiovascular disease, possible birth defects, and poisoning.[161] In vitro studies of nicotine have associated it with cancer, but carcinogenicity has not been demonstrated in vivo.[161] There is inadequate research to show that nicotine is associated with cancer in humans.[178] The risk is probably low from the inhalation of propylene glycol and glycerin.[9] No information is available on the long-term effects of the inhalation of flavors.[29]

E-cigarettes create vapor that consists of fine and ultrafine particles of particulate matter, with the majority of particles in the ultrafine range.[10] The vapor have been found to contain propylene glycol, glycerin, nicotine, flavors, small amounts of toxicants,[10] carcinogens,[9] and heavy metals, as well as metal nanoparticles, and other substances.[10] Exactly what the vapor consists of varies in composition and concentration across and within manufacturers, and depends on the contents of the liquid, the physical and electrical design of the device, and user behavior, among other factors.[2] E-cigarette vapor potentially contains harmful chemicals not found in tobacco smoke.[77] The majority of toxic chemicals found in cigarette smoke are absent in e-cigarette vapor.[179] E-cigarette vapor contains lower concentrations of potentially toxic chemicals than with cigarette smoke.[13] Those which are present, are mostly below 1% of the corresponding levels permissible by workplace safety standards.[110] But workplace safety standards do not recognize exposure to certain vulnerable groups such as people with medical ailments, children, and infants who may be exposed to second-hand vapor.[10] Concern exists that some of the mainstream vapor exhaled by e-cigarette users may be inhaled by bystanders, particularly indoors.[12] E-cigarette use by a parent might lead to inadvertent health risks to offspring.[28] A 2014 review recommended that e-cigarettes should be regulated for consumer safety.[127] There is limited information available on the environmental issues around production, use, and disposal of e-cigarettes that use cartridges.[180] E-cigarettes that are not reusable may contribute to the problem of electronic waste.[135]

Nicotine, a key ingredient[181] in most e-liquids,[notes 5][4] is well-recognized as one of the most addictive substances, as addictive as heroin and cocaine.[24] Addiction is believed to be a disorder of experience-dependent brain plasticity.[183] The reinforcing effects of nicotine play a significant role in the beginning and continuing use of the drug.[184] First-time nicotine users develop a dependence about 32% of the time.[185] Chronic nicotine use involves both psychological and physical dependence.[186] Nicotine-containing e-cigarette vapor induces addiction-related neurochemical, physiological and behavioral changes.[187] Nicotine affects neurological, neuromuscular, cardiovascular, respiratory, immunological and gastrointestinal systems.[188] Neuroplasticity within the brain's reward system occurs as a result of long-term nicotine use, leading to nicotine dependence.[189] The neurophysiological activities that are the basis of nicotine dependence are intricate.[190] It includes genetic components, age, gender, and the environment.[190] Nicotine addiction is a disorder which alters different neural systems such as dopaminergic, glutamatergic, GABAergic, serotoninergic, that take part in reacting to nicotine.[191] Long-term nicotine use affects a broad range of genes associated with neurotransmission, signal transduction, and synaptic architecture.[192] The ability to quitting smoking is affected by genetic factors, including genetically based differences in the way nicotine is metabolized.[193]

The reinforcing effects of drugs of abuse, such as nicotine, are associated with its ability to excite the mesolimbic and dopaminergic systems.[194]
How does the nicotine in e-cigarettes affect the brain?[195] Until about age 25, the brain is still growing.[195] Each time a new memory is created or a new skill is learned, stronger connections – or synapses – are built between brain cells.[195] Young people's brains build synapses faster than adult brains.[195] Because addiction is a form of learning, adolescents can get addicted more easily than adults.[195] The nicotine in e-cigarettes and other tobacco products can also prime the adolescent brain for addiction to other drugs such as cocaine.[195]

Nicotine is a parasympathomimetic stimulant[196] that binds to and activates nicotinic acetylcholine receptors in the brain,[151] which subsequently causes the release of dopamine and other neurotransmitters, such as norepinephrine, acetylcholine, serotonin, gamma-aminobutyric acid, glutamate, endorphins,[197] and several neuropeptides, including proopiomelanocortin-derived α-MSH and adrenocorticotropic hormone.[198] Corticotropin-releasing factor, Neuropeptide Y, orexins, and norepinephrine are involved in nicotine addiction.[199] Continuous exposure to nicotine can cause an increase in the number of nicotinic receptors, which is believed to be a result of receptor desensitization and subsequent receptor upregulation.[197] Long-term exposure to nicotine can also result in downregulation of glutamate transporter 1.[200] Long-term nicotine exposure upregulates cortical nicotinic receptors, but it also lowers the activity of the nicotinic receptors in the cortical vasodilation region.[201] These effects are not easily understood.[201] With constant use of nicotine, tolerance occurs at least partially as a result of the development of new nicotinic acetylcholine receptors in the brain.[197] After several months of nicotine abstinence, the number of receptors go back to normal.[151] The extent to which alterations in the brain caused by nicotine use are reversible is not fully understood.[192] Nicotine also stimulates nicotinic acetylcholine receptors in the adrenal medulla, resulting in increased levels of epinephrine and beta-endorphin.[197] Its physiological effects stem from the stimulation of nicotinic acetylcholine receptors, which are located throughout the central and peripheral nervous systems.[202]

When nicotine intake stops, the upregulated nicotinic acetylcholine receptors induce withdrawal symptoms.[151] These symptoms can include cravings for nicotine, anger, irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger, weight gain, and difficulty concentrating.[203] When trying to quit smoking with vaping a base containing nicotine, symptoms of withdrawal can include irritability, restlessness, poor concentration, anxiety, depression, and hunger.[142] The changes in the brain cause a nicotine user to feel abnormal when not using nicotine.[204] In order to feel normal, the user has to keep his or her body supplied with nicotine.[204] E-cigarettes may reduce cigarette craving and withdrawal symptoms.[205] It is not clear whether e-cigarette use will decrease or increase overall nicotine addiction,[206] but the nicotine content in e-cigarettes is adequate to sustain nicotine dependence.[207] Chronic nicotine use causes a broad range of neuroplastic adaptations, making quitting hard to accomplish.[190] A 2015 study found that users vaping non-nicotine e-liquid exhibited signs of dependence.[208] Experienced users tend to take longer puffs which may result in higher nicotine intake.[112] It is difficult to assess the impact of nicotine dependence from e-cigarette use because of the wide range of e-cigarette products.[207] The addiction potential of e-cigarettes may have risen because as they have progressed, they delivery nicotine better.[209]

A 2015 American Academy of Pediatrics (AAP) policy statement stressed "the potential for these products to addict a new generation of youth to nicotine and reverse more than 50 years of public health gains in tobacco control."[210] The World Health Organization (WHO) is concerned about starting nicotine use among non-smokers,[89] and the National Institute on Drug Abuse said e-cigarettes could maintain nicotine addiction in those who are attempting to quit.[211] The limited available data suggests that the likelihood of abuse from e-cigarettes is smaller than traditional cigarettes.[212] No long-term studies have been done on the effectiveness of e-cigarettes in treating tobacco addiction,[107] but some evidence suggests that dual use of e-cigarettes and traditional cigarettes may be associated with greater nicotine dependence.[3]

There is concern that children may progress from vaping to smoking.[89] Adolescents are likely to underestimate nicotine's addictiveness.[213] Vulnerability to the brain-modifying effects of nicotine, along with youthful experimentation with e-cigarettes, could lead to a lifelong addiction.[78] A long-term nicotine addiction from using a vape may result in using other tobacco products.[214] The majority of addiction to nicotine starts during youth and young adulthood.[215] Adolescents are more likely to become nicotine dependent than adults.[75] The adolescent brain seems to be particularly sensitive to neuroplasticity as a result of nicotine.[192] Minimal exposure could be enough to produce neuroplastic alterations in the very sensitive adolescent brain.[192] A 2014 review found that in studies up to a third of youth who have not tried a traditional cigarette have used e-cigarettes.[10] The degree to which teens are using e-cigarettes in ways the manufacturers did not intend, such as increasing the nicotine delivery, is unknown,[216] as is the extent to which e-cigarette use may lead to addiction or substance dependence in youth.[216]

Because of overlap with tobacco laws and medical drug policies, e-cigarette legislation is being debated in many countries.[179] The revised EU Tobacco Products Directive came into effect in May 2016, providing stricter regulations for e-cigarettes.[217] In February 2010 the US District Court ruled against the FDA's seizure of E-Cigarettes as a "drug-device" and in December 2010 the US Court of Appeals confirmed them to be tobacco products which were by then subject to regulation under the 2009 FSPTC Act.[218] In August 2016, the US FDA extended its regulatory power to include e-cigarettes, cigars, and "all other tobacco products".[219] Large tobacco companies have greatly increased their marketing efforts.[107]

The scientific community in US and Europe are primarily concerned with their possible effect on public health.[220] There is concern among public health experts that e-cigarettes could renormalize smoking, weaken measures to control tobacco,[221] and serve as a gateway for smoking among youth.[222] The public health community is divided over whether to support e-cigarettes, because their safety and efficacy for quitting smoking is unclear.[131] Many in the public health community acknowledge the potential for their quitting smoking and decreasing harm benefits, but there remains a concern over their long-term safety and potential for a new era of users to get addicted to nicotine and then tobacco.[222] There is concern among tobacco control academics and advocates that prevalent universal vaping "will bring its own distinct but as yet unknown health risks in the same way tobacco smoking did, as a result of chronic exposure", among other things.[139]

Medical organizations differ in their views about the health implications of vaping.[223] There is general agreement that e-cigarettes expose users to fewer toxicants than tobacco cigarettes.[103] Some healthcare groups and policy makers have hesitated to recommend e-cigarettes for quitting smoking, because of limited evidence of effectiveness and safety.[103] Some have advocated bans on e-cigarette sales and others have suggested that e-cigarettes may be regulated as tobacco products but with less nicotine content or be regulated as a medicinal product.[106] A 2016 World Health Organization (WHO) report found that the scientific evidence for the effectiveness of vaping for quitting smoking is "scant and of low certainty".[224] Healthcare organizations in the UK in 2015 have encouraged smokers to try e-cigarettes to help them quit smoking and also encouraged e-cigarette users to quit smoking tobacco entirely.[225] In 2016, the US Food and Drug Administration (US FDA) stated that "Although ENDS [electronic nicotine delivery systems] may potentially provide cessation benefits to individual smokers, no ENDS have been approved as effective cessation aids."[226] In 2019 the European Respiratory Society stated that "The long-term effects of ECIG use are unknown, and there is therefore no evidence that ECIGs are safer than tobacco in the long term."[105] Following hundreds of possible cases of severe lung illness and five confirmed deaths associated with vaping in the US, the Centers for Disease Control and Prevention stated on 6 September 2019 that people should consider not using vaping products while their investigation is ongoing.[116]

Regulation of e-cigarettes varies across countries and states, ranging from no regulation to banning them entirely.[287] For instance, e-cigarettes are illegal in Japan, forcing the market to use heated tobacco products for cigarette alternatives.[288] Others have introduced strict restrictions and some have licensed devices as medicines such as in the UK.[157] However, as of February 2018, there is no e-cigarette device that has been given a medical license that is commercially sold or available by prescription in the UK.[289] As of 2015, around two thirds of major nations have regulated e-cigarettes in some way.[290] Because of the potential relationship with tobacco laws and medical drug policies, e-cigarette legislation is being debated in many countries.[179] The companies that make e-cigarettes have been pushing for laws that support their interests.[291] In 2016 the US Department of Transportation banned the use of e-cigarettes on commercial flights.[292] This regulation applies to all flights to and from the US.[292] In 2018, the Royal College of Physicians asked that a balance is found in regulations over e-cigarettes that ensure product safety while encouraging smokers to use them instead of tobacco, as well as keep an eye on any effects contrary to the control agencies for tobacco.[293]

The legal status of e-cigarettes is currently pending in many countries.[10] Many countries such as Brazil, Singapore, Uruguay,[157] and India have banned e-cigarettes.[294] Canada-wide in 2014, they were technically illegal to sell, as no nicotine-containing e-cigarettes are not regulated by Health Canada, but this is generally unenforced and they are commonly available for sale Canada-wide.[295] In 2016, Health Canada announced plans to regulate vaping products.[296] In the US and the UK, the use and sale to adults of e-cigarettes are legal.[297]^:US[298]^:UK The revised EU Tobacco Products Directive came into effect in May 2016, providing stricter regulations for e-cigarettes.[217] It limits e-cigarette advertising in print, on television and radio, along with reducing the level of nicotine in liquids and reducing the flavors used.[299] It does not ban vaping in public places.[300] It requires the purchaser for e-cigarettes to be at least 18 and does not permit buying them for anyone less than 18 years of age.[301] The updated Tobacco Products Directive has been disputed by tobacco lobbyists whose businesses could be impacted by these revisions.[302] As of 8 August 2016, the US FDA extended its regulatory power to include e-cigarettes, e-liquid and all related products.[219] Under this ruling the FDA will evaluate certain issues, including ingredients, product features and health risks, as well their appeal to minors and non-users.[303] The FDA rule also bans access to minors.[303] A photo ID is now required to buy e-cigarettes,[304] and their sale in all-ages vending machines is not permitted in the US.[303] As of August 2017, regulatory compliance deadlines relating to premarket review requirements for most e-cigarette and e-liquid products have been extended from November 2017 to 8 August 2022,[305][306] which attracted a lawsuit filed by the American Heart Association, American Academy of Pediatrics, the Campaign for Tobacco-Free Kids, and other plaintiffs.[307] In May 2016 the US FDA used its authority under the Family Smoking Prevention and Tobacco Control Act to deem e-cigarette devices and e-liquids to be tobacco products, which meant it intended to regulate the marketing, labelling, and manufacture of devices and liquids; vape shops that mix e-liquids or make or modify devices were considered manufacturing sites that needed to register with US FDA and comply with good manufacturing practice regulation.[226] E-cigarette and tobacco companies have recruited lobbyists in an effort to prevent the US FDA from evaluating e-cigarette products or banning existing products already on the market.[308]

In February 2014 the European Parliament passed regulations requiring standardization and quality control for liquids and vaporizers, disclosure of ingredients in liquids, and child-proofing and tamper-proofing for liquid packaging.[309] In April 2014 the US FDA published proposed regulations for e-cigarettes.[310][311] In the US some states tax e-cigarettes as tobacco products, and some state and regional governments have broadened their indoor smoking bans to include e-cigarettes.[312] As of April 2017, 12 US states and 615 localities had prohibited the use of e-cigarettes in venues in which traditional cigarette smoking was prohibited.[67] In 2015, at least 48 states and 2 territories had banned e-cigarette sales to minors.[313]

E-cigarettes containing nicotine have been listed as drug delivery devices in a number of countries, and the marketing of such products has been restricted or put on hold until safety and efficacy clinical trials are conclusive.[314] Since they do not contain tobacco, television advertising in the US is not restricted.[315] Some countries have regulated e-cigarettes as a medical product even though they have not approved them as a smoking cessation aid.[174] A 2014 review stated the emerging phenomenon of e-cigarettes has raised concerns in the health community, governments, and the general public and recommended that e-cigarettes should be regulated to protect consumers.[127] It added, "heavy regulation by restricting access to e-cigarettes would just encourage continuing use of much unhealthier tobacco smoking."[127] A 2014 review said regulation of the e-cigarette should be considered on the basis of reported adverse health effects.[174]

Multiple reports from the U.S. Fire Administration conclude that electronic cigarettes have been combusting and injuring people and surrounding areas.[316][317] The composition of a cigarette is the cause of this, as the cartridges that are meant to contain the liquid mixture are in such close proximity to the battery.[318] A research report by the U.S. Fire Administration supports this, stating that, “Unlike mobile phones, some e-cigarette lithium-ion batteries within e-cigarettes offer no protection to stop the coil overheating” .[317] In 2015 the U.S. Fire Administration noted in their report that electronic cigarettes are not created by Big Tobacco or other tobacco companies, but by independent factories that have little quality control.[317] Because of this low quality control when made, electronic cigarettes have led to numerous incidents in which people are hurt, or in which the surrounding area is damaged.[317][316]

Most incidents in which electronic cigarettes have been known to explode, occurred when the device itself is charging, usually within 10 minutes.[317] When an e-cigarette combusts, it creates a fire hazard, especially if the electronic cigarette is left on its own with no supervision. Multiple case studies have shown that electronic cigarettes are at risk of this while they are charging. The U.S. Fire Administration states that, “E-cigarettes left charging for long period, especially when unattended, have led to fires in homes and cars,” .[317] This can cause two issues. The first issue would be the device causing a fire while charging and while in use, in which a person may be harmed but they can relatively quickly put out the fire with minimal damage to them and their surroundings. Some of the incidents that the U.S. Fire Administrationlooked at portrayed that this scenario only occurred about 8% of the time, leaving 9 people injured and 2 people with serious burns.[317] The second issue would be if the device is left alone charging and the person goes off into another room or leaves the house completely, and the device implodes. In the cases in which fires were started, 52% of the fires were small scale or minor.[317] In those cases people were around to stop the fire, but what about the other cases in which a person doesn't notice the fire or if they are not even in the house when the fire starts? 32% of cases showcase a moderate fire and 4% of cases showcase that the fire destroyed the room the device was in and its contents.[317] Another report from the U.S. Fire Administration states the following, “In 27 incidents, the fire spread was moderate, where the burned area was larger than 6 inches in diameter, but the fire was extinguished by occupants before the fire department arrived. In 10 incidents, the fire spread was major and involved significant portions of a building and required suppression by the fire department,".[316] The U.S. Fire Administration also notes that in most cases, when the device has combusted, the fire produced spreads to nearby clothing, carpets, drapes, etc.[316] About 66% of explosions led to a fire, because of the contents in the radius of the explosion.[316]

They are marketed to men, women, and children as being safer than traditional cigarettes.[319] They are also marketed to non-smokers.[45] E-cigarette marketing is common.[221] There are growing concerns that e-cigarette advertising campaigns unjustifiably focus on young adults, adolescents, and women.[170] Large tobacco companies have greatly increased their marketing efforts.[107] This marketing trend may expand the use of e-cigarettes and contribute to re-glamorizing smoking.[320] Some companies may use e-cigarette advertising to advocate smoking, deliberately, or inadvertently, is an area of concern.[156] A 2014 review said, "the e-cigarette companies have been rapidly expanding using aggressive marketing messages similar to those used to promote cigarettes in the 1950s and 1960s."[10] E-cigarette companies are using methods that were once used by the tobacco industry to persuade young people to starting using cigarettes.[321] E-cigarettes are promoted to a certain extent to forge a vaping culture that entices non-smokers.[321] Themes in e-cigarette marketing, including sexual content and customer satisfaction, are parallel to themes and techniques that have been found to be appealing to youth and young adults in traditional cigarette advertising and promotion.[72] A 2017 review found "The tobacco industry sees a future where ENDS accompany and perpetuate, rather than supplant, tobacco use, especially targeting the youth."[156] E-cigarettes and nicotine are regularly promoted as safe and even healthy in the media and on brand websites, is an area of concern.[28]

While advertising of tobacco products is banned in most countries, television and radio e-cigarette advertising in several countries may be indirectly encouraging traditional cigarette use.[10] E-cigarette advertisements are also in magazines, newspapers, online, and in retail stores.[322] Between 2010 and 2014, e-cigarettes were second only to cigarettes as the top advertised product in magazines.[323] As cigarette companies have acquired the largest e-cigarette brands, they currently benefit from a dual market of smokers and e-cigarette users while simultaneously presenting themselves as agents of harm reduction.[131] This raises concerns about the appropriateness of endorsing a product that directly profits the tobacco industry.[131] There is no evidence that the cigarette brands are selling e-cigarettes as part of a plan to phase out traditional cigarettes, despite some stating to want to cooperate in "harm reduction".[10] E-cigarette advertising for using e-cigarettes as a quitting tool have been seen in the US, UK, and China, which have not been supported by regulatory bodies.[152] In the US, six large e-cigarette businesses spent $59.3 million on promoting e-cigarettes in 2013.[324] In the US and Canada, over $2 million is spent yearly on promoting e-cigarettes online.[321] E-cigarette websites often made unscientific health statements in 2012.[325] The ease to get past the age verification system at e-cigarette company websites allows underage individuals to access and be exposed to marketing.[325] Around half of e-cigarette company websites have a minimum age notice that prohibited underage individuals from entering.[45]

Celebrity endorsements are used to encourage e-cigarette use.[326] A 2012 national US television advertising campaign for e-cigarettes starred Stephen Dorff exhaling a "thick flume" of what the advertisement describes as "vapor, not tobacco smoke", exhorting smokers with the message "We are all adults here, it's time to take our freedom back."[257] Opponents of the tobacco industry state that the blu advertisement, in a context of longstanding prohibition of tobacco advertising on television, seems to have resorted to advertising tactics that got former generations of people in the US addicted to traditional cigarettes.[257] Cynthia Hallett of Americans for Non-Smokers' Rights described the US advertising campaign as attempting to "re-establish a norm that smoking is okay, that smoking is glamorous and acceptable".[257] University of Pennsylvania communications professor Joseph Cappella stated that the setting of the advertisement near an ocean was meant to suggest an association of clean air with the nicotine product.[257] In 2012 and 2013, e-cigarette companies advertised to a large television audience in the US which included 24 million youth.[327] The channels to which e-cigarette advertising reached the largest numbers of youth (ages 12–17) were AMC, Country Music Television, Comedy Central, WGN America, TV Land, and VH1.[327]

From 2011 to 2014, e-cigarette use among youth was rising as e-cigarette advertising increased.[328]

E-cigarettes are heavily promoted across all media outlets.[75] They are vigorously advertised, mostly through the Internet, as a safe substitute to traditional cigarettes, among other things.[12] E-cigarette companies promote their e-cigarette products on Facebook, Instagram,[322] YouTube, and Twitter.[329] They are promoted on YouTube by movies with sexual material and music icons, who encourage minors to "take their freedom back."[156] They have partenered with a number of sports and music icons to promote their products.[330] Tobacco companies intensely market e-cigarettes to youth,[331] with industry strategies including cartoon characters and candy flavors.[332] Fruit flavored e-liquid is the most commonly marketed e-liquid flavor on social media.[333] E-cigarette companies commonly promote that their products contain only water, nicotine, glycerin, propylene glycol, and flavoring but this assertion is misleading as researchers have found differing amounts of heavy metals in the vapor, including chromium, nickel, tin, silver, cadmium, mercury, and aluminum.[77] The widespread assertion that e-cigarettes emit "only water vapor" is not true because the evidence demonstrates e-cigarette vapor contains possibly harmful chemicals such as nicotine, carbonyls, metals, and volatile organic compounds, in addition to particulate matter.[13] Massive advertising included the assertion that they would present little risk to non-users.[334] Though, "disadvantages and side effects have been reported in many articles, and the unfavorable effects of its secondhand vapor have been demonstrated in many studies",[334] and evidence indicates that use of e-cigarettes degrades indoor air quality.[117] Many e-cigarette companies market their products as a smoking cessation aid without evidence of effectiveness.[335] E-cigarette marketing has been found to make unsubstantiated health statements (e.g., that they help one quit smoking) including statements about improving psychiatric symptoms, which may be particularly appealing to smokers with mental illness.[87] E-cigarette marketing advocate weight control and emphasize use of nicotine with many flavors.[336] These marketing angles could particularly entice overweight people, youth, and vulnerable groups.[336] Some e-cigarette companies state that their products are green without supporting evidence which may be purely to increase their sales.[179]

The number of e-cigarettes sold increased every year from 2003 to 2014.[19] In 2015 a slowdown in the growth in usage occurred in the US.[337] As of January 2018, the growth in usage in the UK has slowed down since 2013.[46] As of 2014 there were at least 466 e-cigarette brands.[338] Worldwide e-cigarette sales in 2014 were around US$7 billion.[339] Worldwide e-cigarette sales in 2019 were about $19.3 billion.[43] E-cigarette sales could exceed traditional cigarette sales by 2023.[340] Approximately 30–50% of total e-cigarettes sales are handled on the internet.[12] Established tobacco companies have a significant share of the e-cigarette market.[78][341]

As of 2018, 95% of e-cigarette devices were made in China,[24] mainly in Shenzhen.[342][343] Chinese companies' market share of e-liquid is low.[344] In 2014, online and offline sales starting increases.[345] Since combustible cigarettes are relatively inexpensive in China a lower price may not be large factor in marketing vaping products over there.[345]

In 2015, 80% of all e-cigarette sales in convenience stores in the US were products made by tobacco companies.[346] According to Nielsen Holdings, convenience store e-cigarette sales in the US went down for the first time during the four-week period ending on 10 May 2014.[347] Wells Fargo analyst Bonnie Herzog attributes this decline to a shift in consumers' behavior, buying more specialized devices or what she calls "vapors-tanks-mods (VTMs)" that are not tracked by Nielsen.[347] Wells Fargo estimated that VTMs accounted for 57% of the 3.5 billion dollar market in the US for vapor products in 2015.[348] In 2014, dollar sales of customizable e-cigarettes and e-liquid surpassed sales of cigalikes in the US, even though, overall, customizables are a less expensive vaping option.[349] In 2014, the Smoke-Free Alternatives Trade Association estimated that there were 35,000 vape shops in the US, more than triple the number a year earlier.[350] However the 2015 slowdown in market growth affected VTMs as well.[337] Large tobacco retailers are leading the cigalike market.[351] "We saw the market's sudden recognition that the cigarette industry seems to be in serious trouble, disrupted by the rise of vaping," Mad Money's Jim Cramer stated April 2018.[352] "Over the course of three short days, the tobacco stocks were bent, they were spindled and they were mutilated by the realization that electronic cigarettes have become a serious threat to the old-school cigarette makers," he added.[352] In 2019, a vaping industry organization released a report stating that a possible US ban on e-cigarettes flavors can potentially effect greater than 150,000 jobs around the US.[353]

The leading seller in the e-cigarette market in the US is the Juul e-cigarette,[354] which was introduced in June 2015.[355] As of August 2018, Juul accounts for over 72% of the US e-cigarette market monitored by Nielsen, and its closest competitor—RJ Reynolds' Vuse—makes up less than 10% of the market.[356] Juul rose to popularity quickly, growing by 700% in 2016 alone.[275] On 17 July 2018 Reynolds announced it will debut in August 2018 a pod mod type device similar Juul.[356] The popularity of the Juul pod system has led to a flood of other pod devices hitting the market.[357]

In Canada, e-cigarettes had an estimated value of 140 million CAD in 2015.[358] There are numerous e-cigarette retail shops in Canada.[359] A 2014 audit of retailers in four Canadian cities found that 94% of grocery stores, convenience stores, and tobacconist shops which sold e-cigarettes sold nicotine-free varieties only, while all vape shops stocked at least one nicotine-containing product.[360]

By 2015 the e-cigarette market had only reached a twentieth of the size of the tobacco market in the UK.[361] In the UK in 2015 the "most prominent brands of cigalikes" were owned by tobacco companies, however, with the exception of one model, all the tank types came from "non-tobacco industry companies".[362] Yet some tobacco industry products, while using prefilled cartridges, resemble tank models.[362]

France's e-cigarette market was estimated by Groupe Xerfi to be €130 million in 2015.[363] Additionally, France's e-liquid market was estimated at €265 million.[363] In December 2015, there were 2,400 vape shops in France, 400 fewer than in March of the same year.[363] Industry organization Fivape said the reduction was due to consolidation, not to reduced demand.[363]