Effects of nicotine on human brain development

Last updated

Exposure to nicotine , from conventional or electronic cigarettes during adolescence can impair the developing human brain. [1] E-cigarette use is recognized as a substantial threat to adolescent behavioral health. [notes 1] [3] The use of tobacco products, no matter what type, is almost always started and established during adolescence when the developing brain is most vulnerable to nicotine addiction. [notes 2] [5] Young people's brains build synapses faster than adult brains. [6] Because addiction is a form of learning, adolescents can get addicted more easily than adults. [6] The nicotine in e-cigarettes can also prime the adolescent brain for addiction to other drugs such as cocaine. [6] Exposure to nicotine and its great risk of developing an addiction, are areas of significant concern. [7]

Contents

Nicotine is a parasympathomimetic stimulant [8] that binds to and activates nicotinic acetylcholine receptors in the brain, [9] which subsequently causes the release of dopamine and other neurotransmitters, such as norepinephrine, acetylcholine, serotonin, gamma-aminobutyric acid, glutamate and endorphins. [10] Nicotine interferes with the blood–brain barrier function, and as a consequence raises the risk of brain edema and neuroinflammation. [11] When nicotine enters the brain it stimulates, among other activities, the midbrain dopaminergic neurons situated in the ventral tegmental area and pars compacta. [12]

Nicotine negatively affects the prefrontal cortex of the developing brain. Prenatal nicotine exposure can result in long-term adverse effects to the developing brain. [notes 3] [14] Prenatal nicotine exposure has been associated with dysregulation of catecholaminergic, serotonergic, and other neurotransmitter systems. [15] E-liquid exposure whether intentional or unintentional from ingestion, eye contact, or skin contact can cause adverse effects such as seizures and anoxic brain trauma. [16] A study on the offspring of the pregnant mice, which were exposed to nicotine-containing e-liquid, showed significant behavioral alterations. [17] This indicated that exposure to e-cigarette components in a susceptible time period of brain development could induce persistent behavioral changes. [17]

Effects of nicotine

The health effects of long-term nicotine use is unknown. [18] It may be decades before the long-term health effects of nicotine e-cigarette aerosol (vapor) inhalation is known. [19] Short-term nicotine use excites the autonomic ganglia nerves and autonomic nerves, but chronic use seems to induce negative effects on endothelial cells. [20] Nicotine may result in neuroplasticity modifications in the brain. [21] Nicotine has been demonstrated to alter the amounts of brain-derived neurotrophic factor in humans. [22] Side effects of nicotine include mild headache, headache, dysphoria, depressed mood, irritability, aggression, frustration, impatience, anxiety, sleep disturbances, abnormal dreams, irritability, and dizziness. [23]

The neuroregulation and structural interactions in the brain and lungs from nicotine may interfere with an array of reflexes and responses. [24] These alterations may raise the risk of hypoxia. [24] Continued use of nicotine may result in harmful effects to women's brains because it restricts estrogen signaling. [24] This could lead to making the brain more vulnerable to ischemia. [24] A 2015 review concluded that "Nicotine acts as a gateway drug on the brain, and this effect is likely to occur whether the exposure is from smoking tobacco, passive tobacco smoke or e-cigarettes." [25]

Nicotine may have a profound impact on sleep. [26] The effects on sleep vary after being intoxicated, during withdrawal, and from long-term use. [26] Nicotine may result in arousal and wakefulness, mainly via incitement in the basal forebrain. [27] Nicotine withdrawal, after abstaining from nicotine use in non-smokers, was linked with longer overall length of sleep and REM rebound. [26] A 2016 review states that "Although smokers say they smoke to control stress, studies show a significant increase in cortisol concentrations in daily smokers compared with occasional smokers or nonsmokers. These findings suggest that, despite the subjective effects, smoking may actually worsen the negative emotional states. The effects of nicotine on the sleep-wake cycle through nicotine receptors may have a functional significance. Nicotine receptor stimulation promotes wake time and reduces both total sleep time and rapid eye movement sleep." [7]

Animated nicotine structure. Nicotine3Dan2-12-seconds.gif
Animated nicotine structure.

Effects of nicotine diagram

Comparative risk assessment chart

Comparative risk assessment: Potential harms and benefits of vaping [notes 4] [31]
HarmsBenefits
Increased youth exposure to nicotine and potentially greater initiation of conventional cigarettesReduced disease risk for current smokers who completely switch to e-cigarettes
Slowing cessation by smokers due to nicotine addictionReduced disease morbidity for smokers with existing heart or lung disease who switch to e-cigarettes
Nicotine addiction in former smokers who begin to use e-cigarettes and possibly transition back to smokingPotential for cessation of combustible products
Renormalization of nicotine use and smoking as acceptableFewer users of combustible products in the entire population
Future disease risks for youth who are exposed to nicotine
Increasing the dual use of e-cigarettes with combustible products
Serving as a "gateway" to the initiation of tobacco smoking
Increased disease risk vs. complete cessation among those who use both e-cigarettes and combustible products
Exposure to secondhand aerosol and lack of clean air

Addiction and dependence

Psychological and physical dependence

Nicotine, a key ingredient [32] in most e-liquids, [33] is well-recognized as one of the most addictive substances, as addictive as heroin and cocaine. [34] Addiction is believed to be a disorder of experience-dependent brain plasticity. [35] The reinforcing effects of nicotine play a significant role in the beginning and continuing use of the drug. [36] First-time nicotine users develop a dependence about 32% of the time. [37] Chronic nicotine use involves both psychological and physical dependence. [38] Nicotine-containing e-cigarette aerosol induces addiction-related neurochemical, physiological and behavioral changes. [17]

Nicotine affects neurological, neuromuscular, cardiovascular, respiratory, immunological and gastrointestinal systems. [39] Neuroplasticity within the brain's reward system occurs as a result of long-term nicotine use, leading to nicotine dependence. [40] The neurophysiological activities that are the basis of nicotine dependence are intricate. [41] It includes genetic components, age, gender, and the environment. [41] Pre-existing cognitive and mood disorders may influence the development and maintenance of nicotine dependence. [42]

Nicotine addiction is a disorder which alters different neural systems such as dopaminergic, glutamatergic, GABAergic, serotoninergic, that take part in reacting to nicotine. [43] In 2015 the psychological and behavioral effects of e-cigarettes were studied using whole-body exposure to e-cigarette aerosol, followed by a series of biochemical and behavioral studies. [17] The results showed that nicotine-containing e-cigarette aerosol induces addiction-related neurochemical, physiological and behavioral changes. [17]

Long-term nicotine use affects a broad range of genes associated with neurotransmission, signal transduction, and synaptic architecture. [44] The most well-known hereditary influence related to nicotine dependence is a mutation at rs16969968 in the nicotinic acetylcholine receptor CHRNA5 , resulting in an amino acid alteration from aspartic acid to asparagine. [45] The single-nucleotide polymorphisms (SNPs) rs6474413 and rs10958726 in CHRNB3 are highly correlated with nicotine dependence. [46] Many other known variants within the CHRNB3–CHRNA6 nicotinic acetylcholine receptors are also correlated with nicotine dependence in certain ethnic groups. [46] There is a relationship between CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptors and complete smoking cessation. [47]

Increasing evidence indicates that the genetic variant CHRNA5 predicts the response to smoking cessation medicine. [47] The ability to quitting smoking is affected by genetic factors, including genetically based differences in the way nicotine is metabolized. [48] In the CYP450 system there are 173 genetic variants, which impacts how quickly nicotine is metabolizes by each individual. [49] The speed of metabolism impacts the regularity and quantity of nicotine used. [49] For instance, in people who metabolize nicotine gradually their central nervous system effects of nicotine lasts longer, increasing their probability of dependence, but also increasing ability with quitting smoking. [49]

Stimulation of the brain

The reinforcing effects of drugs of abuse, such as nicotine, are associated with its ability to excite the mesolimbic and dopaminergic systems.
How does the nicotine in e-cigarettes affect the brain? Until about age 25, the brain is still growing. Each time a new memory is created or a new skill is learned, stronger connections - or synapses - are built between brain cells. Young people's brains build synapses faster than adult brains. Because addiction is a form of learning, adolescents can get addicted more easily than adults. The nicotine in e-cigarettes and other tobacco products can also prime the adolescent brain for addiction to other drugs such as cocaine. Recolored Overview of reward structures in the human brain2.png
The reinforcing effects of drugs of abuse, such as nicotine, are associated with its ability to excite the mesolimbic and dopaminergic systems.
How does the nicotine in e-cigarettes affect the brain? Until about age 25, the brain is still growing. Each time a new memory is created or a new skill is learned, stronger connections – or synapses – are built between brain cells. Young people's brains build synapses faster than adult brains. Because addiction is a form of learning, adolescents can get addicted more easily than adults. The nicotine in e-cigarettes and other tobacco products can also prime the adolescent brain for addiction to other drugs such as cocaine.

Nicotine is a parasympathomimetic stimulant [8] that binds to and activates nicotinic acetylcholine receptors in the brain, [9] which subsequently causes the release of dopamine and other neurotransmitters, such as norepinephrine, acetylcholine, serotonin, gamma-aminobutyric acid, glutamate, endorphins, [10] and several neuropeptides, including proopiomelanocortin-derived α-MSH and adrenocorticotropic hormone. [52] Corticotropin-releasing factor, Neuropeptide Y, orexins, and norepinephrine are involved in nicotine addiction. [53]

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. [10] Long-term exposure to nicotine can also result in downregulation of glutamate transporter 1. [54] Long-term nicotine exposure upregulates cortical nicotinic receptors, but it also lowers the activity of the nicotinic receptors in the cortical vasodilation region. [55] These effects are not easily understood. [55]

With constant use of nicotine, tolerance occurs at least partially as a result of the development of new nicotinic acetylcholine receptors in the brain. [10] After several months of nicotine abstinence, the number of receptors go back to normal. [9] The extent to which alterations in the brain caused by nicotine use are reversible is not fully understood. [44] Nicotine also stimulates nicotinic acetylcholine receptors in the adrenal medulla, resulting in increased levels of epinephrine and beta-endorphin. [10] Its physiological effects stem from the stimulation of nicotinic acetylcholine receptors, which are located throughout the central and peripheral nervous systems. [56]

The α4β2 nicotinic receptor subtype is the main nicotinic receptor subtype. [57] Nicotine activates brain receptors which produce sedative as well as pleasurable effects. [58] Chronic nicotinic acetylcholine receptor activation from repeated nicotine exposure can induce strong effects on the brain, including changes in the brain's physiology, that result from the stimulation of regions of the brain associated with reward, pleasure, and anxiety. [59] These complex effects of nicotine on the brain are still not well understood. [59]

Nicotine interferes with the blood–brain barrier function, and as a consequence raises the risk of brain edema and neuroinflammation. [11] When nicotine enters the brain it stimulates, among other activities, the midbrain dopaminergic neurons situated in the ventral tegmental area and pars compacta. [12] It induces the release of dopamine in different parts of the brain, such as the nucleus accumbens, amygdala, and hippocampus. [12] Ghrelin-induced dopamine release occurs as a result of the activation of the cholinergic–dopaminergic reward link in the ventral tegmental area, a critical part of the reward areas in the brain related with reinforcement. [60] Ghrelin signaling may affect the reinforcing effects of drug dependence. [60]

Discontinuing nicotine use

When nicotine intake stops, the upregulated nicotinic acetylcholine receptors induce withdrawal symptoms. [9] These symptoms can include cravings for nicotine, anger, irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger, weight gain, and difficulty concentrating. [61] When trying to quit smoking with vaping a base containing nicotine, symptoms of withdrawal can include irritability, restlessness, poor concentration, anxiety, depression, and hunger. [62] The changes in the brain cause a nicotine user to feel abnormal when not using nicotine. [63] In order to feel normal, the user has to keep his or her body supplied with nicotine. [63] E-cigarettes may reduce cigarette craving and withdrawal symptoms. [64]

Limiting tobacco consumption with the use of campaigns that portray cigarette smoking as unacceptable and harmful have been enacted; though, advocating for the use of e-cigarettes jeopardizes this because of the possibility of escalating nicotine addiction. [65] It is not clear whether e-cigarette use will decrease or increase overall nicotine addiction, [66] but the nicotine content in e-cigarettes is adequate to sustain nicotine dependence. [67] Chronic nicotine use causes a broad range of neuroplastic adaptations, making quitting hard to accomplish. [41]

A 2015 study found that users vaping non-nicotine e-liquid exhibited signs of dependence. [68] Experienced users tend to take longer puffs which may result in higher nicotine intake. [69] It is difficult to assess the impact of nicotine dependence from e-cigarette use because of the wide range of e-cigarette products. [67] The addiction potential of e-cigarettes may have risen because as they have progressed, they delivery nicotine better. [70] A 2016 review states that "The highly addictive nature of nicotine is responsible for its widespread use and difficulty with quitting." [7]

Youth e-cigarette use is rising. Youth e-cigarette use is rising.jpg
Youth e-cigarette use is rising.

Young adults and youth

Addiction and dependence

This video from the US Surgeon General advises parents to "Know the Risks," and highlights how e-cigarettes have the potential to cause lasting harm to the health of young users, especially their brain development, which continues until about age 25. [72]

E-cigarettes use by children and adolescents may result in nicotine addiction. [73] :C [74] :A Following the possibility of nicotine addiction via e-cigarettes, there is concern that children may start smoking cigarettes. [75] Adolescents are likely to underestimate nicotine's addictiveness. [76] Vulnerability to the brain-modifying effects of nicotine, along with youthful experimentation with e-cigarettes, could lead to a lifelong addiction. [77] A long-term nicotine addiction from using a vape may result in using other tobacco products. [78]

The majority of addiction to nicotine starts during youth and young adulthood. [79] Adolescents are more likely to become nicotine dependent than adults. [80] The adolescent brain seems to be particularly sensitive to neuroplasticity as a result of nicotine. [44] Minimal exposure could be enough to produce neuroplastic alterations in the very sensitive adolescent brain. [44] Exposure to nicotine during adolescence may increase vulnerability to getting addicted to cocaine and other drugs. [81]

The ability of e-cigarettes to deliver comparable or higher amounts of nicotine compared to traditional cigarettes raises concerns about e-cigarette use generating nicotine dependence among young people. [82] Youth who believe they are vaping without nicotine could still be inhaling nicotine because there are significant differences between declared and true nicotine content. [83]

A 2016 US Surgeon General report concluded that e-cigarette use among young adults and youths is of public health concern. [71] Various organizations, [84] including the International Union Against Tuberculosis and Lung Disease, the American Academy of Pediatrics, the American Cancer Society, the Centers for Disease Control and Prevention, and the US Food and Drug Administration (US FDA), have expressed concern that e-cigarette use could increase the prevalence of nicotine addiction in youth. [85] :IUATLD [86] :AAP [87] :ACS [79] :CDC [88] :US FDA

Flavored tobacco is especially enticing to youth, and certain flavored tobacco products increase addiction. [14] There is concern that flavored e-cigarettes could have a similar impact on youth. [14] The extent to which teens are using e-cigarettes may lead to addiction or substance dependence in youth, is unknown. [89] A 2017 review noted that "adolescents experience symptoms of dependence at lower levels of nicotine exposure than adults. Consequently, it is harder to reverse addiction originating in this stage compared with later in life." [90]

Adolescents are particularly susceptible to nicotine addiction: the majority (90%) of smokers start before the age of 18, a fact that has been utilized by tobacco companies for decades in their teen-targeted advertising, marketing and even product design. [34] E-cigarette marketing tactics have the possibility to glamorize smoking and enticing children and never smokers, even when such outcomes are unintended. [91] Adolescents may show signs of dependence with even infrequent nicotine use; sustained nicotine exposure leads to upregulation of the receptors in the prefrontal cortex, pathways which are involved in cognitive control, and which are not fully matured until the mid-twenties. [34] Such disruption of neural circuit development may lead to long-term cognitive and behavioral impairment and has been associated with depression and anxiety. [34]

The nicotine content in e-cigarettes varies widely by product and by use. [34] Refill solutions may contain anywhere from 1.8% nicotine (18 mg/mL) to over 5% (59 mg/mL). [34] Nicotine delivery may be affected by the device itself, for example, by increasing the voltage which changes the aerosol delivered, or by "dripping"—a process of inhaling liquid poured directly onto coils. [34] The latest generation of e-cigarettes, "pod products," such as Juul, have the highest nicotine content (59 mg/mL), in protonated salt, rather than the free-base nicotine form found in earlier generations, which makes it easier for less experienced users to inhale. [34] Despite the clear presence of nicotine in e-cigarettes, adolescents often do not recognize this fact, potentially fueling misperceptions about the health risks and addictive potential of e-cigarettes. [34]

In the US, the unprecedented increase in current (past-month) users from 11.7% of high school students in 2017 to 20.8% in 2018 would imply dependence, if not addiction, given what we know about nicotine and its effects on the adolescent brain. [34] Two recent studies in 2018 utilized validated measures to identify nicotine dependence in e-cigarette using adolescents. [34] Exposure to nicotine from certain types of e-cigarettes may be higher than that from traditional cigarettes. [34] For example, in a study in 2018 of adolescent pod users, their urinary cotinine (a breakdown product used to measure nicotine exposure) levels were higher than levels seen in adolescent cigarette smokers. [34]

Graphic from the 2019 US Surgeon General's report entitled Use of Two or More Tobacco Products. Use of Two or More Tobacco Products.png
Graphic from the 2019 US Surgeon General's report entitled Use of Two or More Tobacco Products.

Effects on the brain

Both preadolescence and adolescence are developmental periods associated with increased vulnerability to nicotine addiction, and exposure to nicotine during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. [93] Nicotine has more significant and durable damaging effects on adolescent brains compared to adult brains, the former suffering more harmful effects. [94] Preclinical animal studies have shown that in rodent models, nicotinic acetylcholine receptor signaling is still actively changing during adolescence, with higher expression and functional activity of nicotinic acetylcholine receptors in the forebrain of adolescent rodents compared to their adult counterparts. [94]

In rodent models, nicotine actually enhances neuronal activity in several reward-related regions and does so more robustly in adolescents than in adults. [94] This increased sensitivity to nicotine in the reward pathways of adolescent rats is associated with enhanced behavioral responses, such as strengthening the stimulus response reward for administration of nicotine. [94] In conditioned place-preference tests—where reward is measured by the amount of time animals spend in an environment where they receive nicotine compared to an environment where nicotine is not administered—adolescent rodents have shown an increased sensitivity to the rewarding effects of nicotine at very low doses (0.03 mg/kg) and exhibited a unique vulnerability to oral self-administration during the early-adolescent period. [94]

Adolescent rodents also have shown higher levels of nicotine self-administration than adults, decreased sensitivity to the aversive effects of nicotine, and less prominent withdrawal symptoms following chronic nicotine exposure. [94] This characteristic in rodent models of increased positive and decreased negative short-term effects of nicotine during adolescence (versus adulthood) highlights the possibility that human adolescents might be particularly vulnerable to developing dependency to and continuing to use e-cigarettes. [94]

The teen years are critical for brain development, which continues into young adulthood. [30] Young people who use nicotine products in any form, including e-cigarettes, are uniquely at risk for long-lasting effects. [30] Because nicotine affects the development of the brain's reward system, continued e-cigarette use can not only lead to nicotine addiction, but it also can make other drugs such as cocaine and methamphetamine more pleasurable to a teen's developing brain. [30] Concerns exist in respect to adolescence vaping due to studies indicating nicotine may potentially have harmful effects on the brain. [95] Nicotine exposure during adolescence adversely affects cognitive development. [1]

Children are more sensitive to nicotine than adults. [77] The use of products containing nicotine in any form among youth, including in e-cigarettes, is unsafe. [28] Animal research indicates strong evidence that the limbic system, which modulates drug reward, cognition, and emotion, is growing during adolescence and is particularly vulnerable to the long lasting effects of nicotine. [3] In youth, nicotine is associated with cognitive impairment [3] as well as the chance of getting addicted for life. [96]

The adolescent's developing brain is especially sensitive to the harmful effects of nicotine. [97] A short period of regular or occasional nicotine exposure in adolescence exerts long-term neurobehavioral damage. [97] Risks of exposing the developing brain to nicotine include mood disorders and permanent lowering of impulse control. [6] The rise in vaping is of great concern because the parts encompassing in greater cognitive activities including the prefrontal cortex of the brain continues to develop into the 20s. [1] Nicotine exposure during brain development may hamper growth of neurons and brain circuits, effecting brain architecture, chemistry, and neurobehavioral activity. [1]

Nicotine changes the way synapses are formed, which can harm the parts of the brain that control attention and learning. [6] Preclinical studies indicate that teens being exposed to nicotine interferes with the structural development of the brain, inducing lasting alterations in the brain's neural circuits. [98] Nicotine affects the development of brain circuits that control attention and learning. [30] Other risks include mood disorders and permanent problems with impulse control—failure to fight an urge or impulse that may harm oneself or others. [30] Each e-cigarette brand differs in the exact amount of ingredients and nicotine in each product. [98] Therefore, little is known regarding the health consequences of each brand to the growing brains of youth. [98]

E-cigarettes are a source of potential developmental toxicants. [99] E-cigarette aerosol, e-liquids, flavoring, and the metallic coil can cause oxidative stress, and the growing brain is uniquely susceptible to the detrimental effects of oxidative stress. [100] As indicated in the limited research from animal studies, there is the potential for induced changes in neurocognitive growth among children who have been subjected to e-cigarette aerosols consisting of nicotine. [29] The US FDA stated in 2019 that some people who use e-cigarettes have experienced seizures, with most reports involving youth or young adult users. [101] Inhaling lead from e-cigarette aerosol can induce serious neurologic injury, notably to the growing brains of children. [102]

A 2017 review states that "Because the brain does not reach full maturity until the mid-20s, restricting sales of electronic cigarettes and all tobacco products to individuals aged at least 21 years and older could have positive health benefits for adolescents and young adults." [90] Adverse effects to the health of children is mostly not known. [103] Children subjected to e-cigarettes had a higher likelihood of having more than one adverse effect and effects were more significant, than with children subjected to traditional cigarettes. [103] Significant harmful effects were cyanosis, nausea, and coma, among others. [103]

Effects of nicotine on the human brain. Nicotine brain.jpg
Effects of nicotine on the human brain.

Effects of nicotine on fetal development diagram

Fetal development

There is accumulating research concerning the negative effects of nicotine on prenatal brain development. [notes 5] [110] Vaping during pregnancy can be harmful to the fetus. [111] There is no supporting evidence demonstrating that vaping is safe for use in pregnant women. [104] Nicotine accumulates in the fetus because it goes through the placenta. [112] Nicotine has been found in placental tissue as early as seven weeks of embryonic gestation, and nicotine concentrations are higher in fetal fluids than in maternal fluids. [15] Nicotine can lead to vasoconstriction of uteroplacental vessels, reducing the delivery of both nutrients and oxygen to the fetus. [113]

As a result, nutrition is re-distributed to prioritize vital organs, such as the heart and the brain, at the cost of less vital organs, such as the liver, kidneys, adrenal glands, and pancreas, leading to underdevelopment and functional disorders later in life. [113] Nicotine attaches to nicotinic acetylcholine receptors in the fetus brain. [90] The stage when the human brain is developing is possibly the most sensitive time period to the effects of nicotine. [104] When the brain is being developed, activating or desensitizing nicotinic acetylcholine receptors by being exposed to nicotine can result in long-term developmental disturbances. [90]

Prenatal nicotine exposure has been associated with dysregulation of catecholaminergic, serotonergic, and other neurotransmitter systems. [15] Prenatal nicotine exposure is associated with preterm birth, [76] stillbirth, [76] sudden infant death syndrome, [104] auditory processing complications, changes to the corpus callosum, [105] changes in brain metabolism, [106] changes in neurological systems, [104] changes in neurotransmitter systems, [106] changes in normal brain development, lower birth weights compared to other infants, [104] and a reduction in brain weight. [108]

A 2017 review states, "because nicotine targets the fetal brain, damage can be present, even when birth weight is normal." [90] A 2014 US Surgeon General report found "that nicotine adversely affects maternal and fetal health during pregnancy, and that exposure to nicotine during fetal development has lasting adverse consequences for brain development." [14] Nicotine prenatal exposure is associated with behavioral abnormalities in adults and children. [107] Prenatal nicotine exposure may result in persisting, multigenerational changes in the epigenome. [3]

Health effects of using e-cigarettes. Electronic Cigarettes, What is the bottom line CDC (nicotine effects no numeral).svg
Health effects of using e-cigarettes.

Effects of e-cigarette liquid

E-liquid exposure whether intentional or unintentional from ingestion, eye contact, or skin contact can cause adverse effects such as seizures and anoxic brain trauma. [16] The nicotine in e-liquids readily absorbs into the bloodstream when a person uses an e-cigarette. [30] Upon entering the blood, nicotine stimulates the adrenal glands to release the hormone epinephrine. [30] Epinephrine stimulates the central nervous system and increases blood pressure, breathing, and heart rate. [30]

As with most addictive substances, nicotine increases levels of a chemical messenger in the brain called dopamine, which affects parts of the brain that control reward (pleasure from natural behaviors such as eating). [30] These feelings motivate some people to use nicotine again and again, despite possible risks to their health and well-being. [30]

A 2015 study on the offspring of the pregnant mice, which were exposed to nicotine-containing e-liquid, showed significant behavioral alterations. [17] This indicated that exposure to e-cigarette components in a susceptible time period of brain development could induce persistent behavioral changes. [17] E-cigarette aerosols without containing nicotine could harm the growing conceptus. [115] This indicates that the ingredients in the e-liquid, such as the flavors, could be developmental toxicants. [115]

Notes

  1. From prenatal development through adolescence and early adulthood, exposure to nicotine poses a serious threat, because these are critical times for brain development and brain plasticity. [2] Furthermore, youth and young adults are more vulnerable than adults to the long-term consequences of nicotine exposure, including susceptibility to nicotine addiction and potentially reduced impulse control, deficits in attention and cognition, and mood disorders. [2]
  2. A 2018 review found "Nicotine is the third most commonly used substance by adolescents and use of electronic cigarettes has become twice as popular as traditional tobacco products. Concomitantly, e-cigarettes have been found to increase the risk for transitioning to more traditional tobacco cigarettes. Although acute administration of nicotine may enhance cognition in teens and young adults, especially memory and attention, chronic use has been linked with attention and working memory deficits in teens. Acute withdrawal from nicotine in adolescent users has also been associated with abnormal reward processing, working memory, and verbal memory fMRI tasks, highlighting the necessity to measure last use of nicotine prior to neurocognitive assessment." [4]
  3. Studies of the effects of maternal smoking of conventional cigarettes during pregnancy, coupled with preclinical literature examining the effects of maternal self-administration of nicotine during pregnancy, suggest that e-cigarette use by mothers during pregnancy presents a wide variety of risks to fetal, infant, and child brain development. [13]
  4. The long-term health risks of e-cigarettes will not be known for decades, although evidence to date suggests that they are generally less harmful than combustible tobacco products. [31] However, less harmful is not the same as harmless. [31] A substantial amount of evidence is available on some components of the e-cigarette aerosols inhaled by e-cigarette users. [31] For many people, exposure to e-cigarette aerosol could occur across much of the life span, beginning in adolescence and even in childhood, when the lungs and brain are still developing. [31]
  5. Fetal exposure to nicotine during pregnancy can result in multiple adverse consequences, including sudden infant death syndrome, altered corpus callosum, auditory processing deficits, effects on behaviors and obesity, and deficits in attention and cognition. [109]

Bibliography

Related Research Articles

<span class="mw-page-title-main">Nicotine</span> Chemical stimulant produced by some plants

Nicotine is a naturally produced alkaloid in the nightshade family of plants and is widely used recreationally as a stimulant and anxiolytic. As a pharmaceutical drug, it is used for smoking cessation to relieve withdrawal symptoms. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits where it acts as a receptor antagonist.

<span class="mw-page-title-main">Cigarette</span> Small roll of tobacco made to be smoked

A cigarette is a narrow cylinder containing a combustible material, typically tobacco, that is rolled into thin paper for smoking. The cigarette is ignited at one end, causing it to smolder; the resulting smoke is orally inhaled via the opposite end. Cigarette smoking is the most common method of tobacco consumption. The term cigarette, as commonly used, refers to a tobacco cigarette, but the word is sometimes used to refer to other substances, such as a cannabis cigarette or a herbal cigarette. A cigarette is distinguished from a cigar by its usually smaller size, use of processed leaf, and paper wrapping, which is typically white.

<span class="mw-page-title-main">Cotinine</span> Alkaloid found in tobacco

Cotinine is an alkaloid found in tobacco and is also the predominant metabolite of nicotine, typically used as a biomarker for exposure to tobacco smoke. Cotinine is currently being studied as a treatment for depression, post-traumatic stress disorder (PTSD), schizophrenia, Alzheimer's disease and Parkinson's disease. Cotinine was developed as an antidepressant as a fumaric acid salt, cotinine fumarate, to be sold under the brand name Scotine, but it was never marketed.

<span class="mw-page-title-main">Vaporizer (inhalation device)</span> Device to vaporize substances for inhalation

A vaporizer or vaporiser, colloquially known as a vape, is a device used to vaporize substances for inhalation. Plant substances can be used, commonly cannabis, tobacco, or other herbs or blends of essential oil. However, they are most commonly filled with a combination propylene glycol, glycerin, and drugs such as nicotine or tetrahydrocannabinol as a liquid solution.

<span class="mw-page-title-main">Nicotine replacement therapy</span> Treatment for tobacco use disorder

Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting tobacco smoking by about 55%. Often it is used along with other behavioral techniques. NRT has also been used to treat ulcerative colitis. Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler. The use of multiple types of NRT at a time may increase effectiveness.

<span class="mw-page-title-main">Chain smoking</span> Practice of smoking several cigarettes/cigars in succession

Chain smoking is the practice of smoking several cigarettes in succession, sometimes using the ember of a finishing cigarette to light the next. The term chain smoker often also refers to a person who smokes relatively constantly, though not necessarily chaining each cigarette. The term applies primarily to cigarettes, although it can be used to describe incessant cigar and pipe smoking as well as vaping. It is a common indicator of addiction.

<span class="mw-page-title-main">Nicotine poisoning</span> Medical condition

Nicotine poisoning describes the symptoms of the toxic effects of nicotine following ingestion, inhalation, or skin contact. Nicotine poisoning can potentially be deadly, though serious or fatal overdoses are rare. Historically, most cases of nicotine poisoning have been the result of use of nicotine as an insecticide. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness, or due to unintended ingestion of tobacco or tobacco products or consumption of nicotine-containing plants.

NicVAX is an experimental conjugate vaccine intended to reduce or eliminate physical dependence to nicotine. According to the U.S. National Institute of Drug Abuse, NicVAX can potentially be used to inoculate against nicotine addiction. This proprietary vaccine is being developed by Nabi Biopharmaceuticals of Rockville, MD. with the support from the U.S. National Institute on Drug Abuse. NicVAX consists of the hapten 3'-aminomethylnicotine which has been conjugated (attached) to Pseudomonas aeruginosa exotoxin A.

<span class="mw-page-title-main">Electronic cigarette</span> Device that vaporizes a liquid nicotine solution for inhalation

An electronic cigarette (e-cigarette) or vape is a device that simulates tobacco smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such, using an e-cigarette is often called "vaping". The atomizer is a heating element that vaporizes a liquid solution called e-liquid, which quickly cools into an aerosol of tiny droplets, vapor and air. The vapor mainly comprises propylene glycol and/or glycerin, usually with nicotine and flavoring. Its exact composition varies, and depends on several things including user behavior.

<span class="mw-page-title-main">Nicotine dependence</span> Chronic disease

Nicotine dependence is a state of dependence upon nicotine. Nicotine dependence is a chronic, relapsing disease defined as a compulsive craving to use the drug, despite social consequences, loss of control over drug intake, and emergence of withdrawal symptoms. Tolerance is another component of drug dependence. Nicotine dependence develops over time as a person continues to use nicotine. The most commonly used tobacco product is cigarettes, but all forms of tobacco use and e-cigarette use can cause dependence. Nicotine dependence is a serious public health problem because it leads to continued tobacco use, which is one of the leading preventable causes of death worldwide, causing more than 8 million deaths per year.

<span class="mw-page-title-main">Flavored tobacco</span> Tobacco product with added flavorings

Flavored tobacco products — tobacco products with added flavorings — include types of cigarettes, cigarillos and cigars, hookahs and hookah tobacco, various types of smokeless tobacco, and more recently electronic cigarettes. Flavored tobacco products are especially popular with youth and have therefore become targets of regulation in several countries.

The use of electronic cigarettes (vaping) carries health risks. The risk depends on the fluid and varies according to design and user behavior. In the United Kingdom, vaping is considered by some to be around 95% less harmful than tobacco after a controversial landmark review by Public Health England.

The scientific community in the United States and Europe are primarily concerned with the possible effect of electronic cigarette use on public health. There is concern among public health experts that e-cigarettes could renormalize smoking, weaken measures to control tobacco, and serve as a gateway for smoking among youth. The public health community is divided over whether to support e-cigarettes, because their safety and efficacy for quitting smoking is unclear. 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. 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.

<span class="mw-page-title-main">Construction of electronic cigarettes</span> Engineering and chemistry of e-cigarettes

An electronic cigarette is a handheld battery-powered vaporizer that simulates smoking, but without tobacco combustion. E-cigarette components include a mouthpiece, a cartridge, a heating element/atomizer, a microprocessor, a battery, and some of them have an LED light on the end. An atomizer consists of a small heating element, or coil, that vaporizes e-liquid and a wicking material that draws liquid onto the coil. When the user inhales a flow sensor activates the heating element that atomizes the liquid solution; most devices are manually activated by a push-button. The e-liquid reaches a temperature of roughly 100–250 °C (212–482 °F) within a chamber to create an aerosolized vapor. The user inhales an aerosol, which is commonly but inaccurately called vapor, rather than cigarette smoke. Vaping is different from smoking, but there are some similarities, including the hand-to-mouth action of smoking and an aerosol that looks like cigarette smoke. The aerosol provides a flavor and feel similar to tobacco smoking. There is a learning curve to use e-cigarettes properly. E-cigarettes are cigarette-shaped, and there are many other variations. E-cigarettes that resemble pens or USB memory sticks are also sold that may be used unobtrusively.

<span class="mw-page-title-main">Composition of electronic cigarette aerosol</span>

The chemical composition of the electronic cigarette aerosol varies across and within manufacturers. Limited data exists regarding their chemistry. However, researchers at Johns Hopkins University analyzed the vape clouds of popular brands such as Juul and Vuse, and found "nearly 2,000 chemicals, the vast majority of which are unidentified."

<span class="mw-page-title-main">Vape shop</span> Shop selling vaping products

A vape shop is a retail outlet specializing in the selling of vaping products, though shops selling derived psychoactive cannabis products have increased in the United States since the passage of the 2018 Farm Bill. There are also online vape shops. A vape shop offers a range of vaping products. The majority of vape shops do not sell vaping products that are from "Big Tobacco" companies. In 2013, online search engine searches on vape shops surpassed searches on e-cigarettes. Around a third of all sales of vaping products in one US state took place in vape shops. Big Tobacco believes the independent vape market is a threat to their interests.

A heated tobacco product (HTP) is a tobacco product that heats the tobacco at a lower temperature than conventional cigarettes. These products contain nicotine, which is a highly addictive chemical. The heat generates an aerosol or smoke to be inhaled from the tobacco, which contains nicotine and other chemicals. HTPs may also contain additives not found in tobacco, including flavoring chemicals. HTPs generally heat tobacco to temperatures under 600 °C (1100 °F), a lower temperature than conventional cigarettes.

<span class="mw-page-title-main">Pod mod</span> Type of electronic cigarette

Pod mods are a type of electronic cigarette used to vape nicotine through a mouthpiece connected to the body of the device by magnets. These devices are a newer generation of e-cigarettes that are often marketed to a younger crowd that do not wish to attract attention gained through regular e-cigarettes or traditional tobacco-burning cigarettes. Pod mods contain a disposable cartridge and coils.

Electronic cigarettes are marketed to smoking and non-smoking men, women, and children as being safer than cigarettes. In the 2010s, large tobacco businesses accelerated their marketing spending on vape products, similar to the strategies traditional cigarette companies used in the 1950s and 1960s.

Nicotine salts are salts formed from nicotine and an acid. They are found naturally in tobacco leaves. Various acids can be used, leading to different conjugate bases paired with the ammonium form of nicotine.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 England, Lucinda J.; Bunnell, Rebecca E.; Pechacek, Terry F.; Tong, Van T.; McAfee, Tim A. (2015). "Nicotine and the Developing Human". American Journal of Preventive Medicine. 49 (2): 286–93. doi:10.1016/j.amepre.2015.01.015. ISSN   0749-3797. PMC   4594223 . PMID   25794473.
  2. 1 2 3 4 5 SGUS 2016, p. 113; Chapter 3.
  3. 1 2 3 4 5 Yuan, Menglu; Cross, Sarah J.; Loughlin, Sandra E.; Leslie, Frances M. (2015). "Nicotine and the adolescent brain". The Journal of Physiology. 593 (16): 3397–3412. doi:10.1113/JP270492. ISSN   0022-3751. PMC   4560573 . PMID   26018031.
  4. Lisdahl, Krista M.; Sher, Kenneth J.; Conway, Kevin P.; Gonzalez, Raul; Feldstein Ewing, Sarah W.; Nixon, Sara Jo; Tapert, Susan; Bartsch, Hauke; Goldstein, Rita Z.; Heitzeg, Mary (2018). "Adolescent brain cognitive development (ABCD) study: Overview of substance use assessment methods". Developmental Cognitive Neuroscience. 32: 80–96. doi:10.1016/j.dcn.2018.02.007. ISSN   1878-9293. PMC   6375310 . PMID   29559216.
  5. 1 2 "Youth and Tobacco". United States Food and Drug Administration. 24 June 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  6. 1 2 3 4 5 6 7 8 9 10 11 12 "Know the Risks". Surgeon General of the United States. 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. 1 2 3 Siqueira, Lorena M. (2016). "Nicotine and Tobacco as Substances of Abuse in Children and Adolescents". Pediatrics. 139 (1): e20163436. doi: 10.1542/peds.2016-3436 . ISSN   0031-4005. PMID   27994114. S2CID   2451568.
  8. 1 2 Richard Beebe; Jeff Myers (19 July 2012). Professional Paramedic, Volume I: Foundations of Paramedic Care. Cengage Learning. pp. 640–. ISBN   978-1-133-71465-1.
  9. 1 2 3 4 Bullen, Christopher (2014). "Electronic Cigarettes for Smoking Cessation". Current Cardiology Reports. 16 (11): 538. doi:10.1007/s11886-014-0538-8. ISSN   1523-3782. PMID   25303892. S2CID   2550483.
  10. 1 2 3 4 5 Drug Therapeutics, Bulletin (2014). "Republished: Nicotine and health". BMJ. 349 (nov26 9): 2014.7.0264rep. doi:10.1136/bmj.2014.7.0264rep. ISSN   1756-1833. PMID   25428425. S2CID   45426626.
  11. 1 2 Sajja, Ravi K; Rahman, Shafiqur; Cucullo, Luca (2016). "Drugs of abuse and blood–brain barrier endothelial dysfunction: A focus on the role of oxidative stress". Journal of Cerebral Blood Flow & Metabolism. 36 (3): 539–54. doi:10.1177/0271678X15616978. ISSN   0271-678X. PMC   4794105 . PMID   26661236.
  12. 1 2 3 Subramaniyan, Manivannan; Dani, John A. (2015). "Dopaminergic and cholinergic learning mechanisms in nicotine addiction". Annals of the New York Academy of Sciences. 1349 (1): 46–63. Bibcode:2015NYASA1349...46S. doi:10.1111/nyas.12871. ISSN   0077-8923. PMC   4564314 . PMID   26301866.
  13. SGUS 2016, p. 124; Chapter 3.
  14. 1 2 3 4 5 Brandon, T. H.; Goniewicz, M. L.; Hanna, N. H.; Hatsukami, D. K.; Herbst, R. S.; Hobin, J. A.; Ostroff, J. S.; Shields, P. G.; Toll, B. A.; Tyne, C. A.; Viswanath, K.; Warren, G. W. (2015). "Electronic Nicotine Delivery Systems: A Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology". Clinical Cancer Research. 21 (3): 514–525. doi: 10.1158/1078-0432.CCR-14-2544 . ISSN   1078-0432. PMID   25573384. S2CID   34471339.
  15. 1 2 3 4 5 6 SGUS 2016, p. 108; Chapter 3.
  16. 1 2 Stratton 2018, p. Summary, Conclusion 14-2.; 9.
  17. 1 2 3 4 5 6 7 Hiemstra, Pieter S.; Bals, Robert (2016). "Basic science of electronic cigarettes: assessment in cell culture and in vivo models". Respiratory Research. 17 (1): 127. doi: 10.1186/s12931-016-0447-z . ISSN   1465-993X. PMC   5055681 . PMID   27717371. Creative Commons by small.svg  This article incorporates text by Pieter S. Hiemstra and Robert Bals available under the CC BY 4.0 license.
  18. Franck, Caroline; Filion, Kristian B.; Kimmelman, Jonathan; Grad, Roland; Eisenberg, Mark J. (2016). "Ethical considerations of e-cigarette use for tobacco harm reduction". Respiratory Research. 17 (1): 53. doi: 10.1186/s12931-016-0370-3 . ISSN   1465-993X. PMC   4869264 . PMID   27184265. Creative Commons by small.svg  This article incorporates text by Caroline Franck, Kristian B. Filion, Jonathan Kimmelman, Roland Grad and Mark J. Eisenberg available under the CC BY 4.0 license.
  19. Golub, Justin S.; Samy, Ravi N. (2015). "Preventing or reducing smoking-related complications in otologic and neurotologic surgery". Current Opinion in Otolaryngology & Head and Neck Surgery. 23 (5): 334–340. doi:10.1097/MOO.0000000000000184. ISSN   1068-9508. PMID   26339963. S2CID   205830424.
  20. Toda, Noboru; Toda, Hiroshi (2010). "Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine". European Journal of Pharmacology. 649 (1–3): 1–13. doi:10.1016/j.ejphar.2010.09.042. ISSN   0014-2999. PMID   20868673.
  21. SA, Meo; SA, Al Asiri (2014). "Effects of electronic cigarette smoking on human health" (PDF). Eur Rev Med Pharmacol Sci. 18 (21): 3315–9. PMID   25487945.
  22. Machaalani, Rita; Chen, Hui (2018). "Brain derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB) and nicotine". NeuroToxicology. 65: 186–195. doi:10.1016/j.neuro.2018.02.014. hdl: 10453/122789 . ISSN   0161-813X. PMID   29499216. S2CID   3688206.
  23. "Nicotine Side Effects". Drugs.com. 21 January 2019.
  24. 1 2 3 4 Schraufnagel, Dean E.; Blasi, Francesco; Drummond, M. Bradley; Lam, David C. L.; Latif, Ehsan; Rosen, Mark J.; Sansores, Raul; Van Zyl-Smit, Richard (2014). "Electronic Cigarettes. A Position Statement of the Forum of International Respiratory Societies". American Journal of Respiratory and Critical Care Medicine. 190 (6): 611–618. doi:10.1164/rccm.201407-1198PP. ISSN   1073-449X. PMID   25006874. S2CID   43763340.
  25. Kandel, Denise; Kandel, Eric (2015). "The Gateway Hypothesis of substance abuse: developmental, biological and societal perspectives". Acta Paediatrica. 104 (2): 130–137. doi:10.1111/apa.12851. ISSN   0803-5253. PMID   25377988. S2CID   33575141.
  26. 1 2 3 Garcia, Alexandra N.; Salloum, Ihsan M. (2015). "Polysomnographic sleep disturbances in nicotine, caffeine, alcohol, cocaine, opioid, and cannabis use: A focused review". The American Journal on Addictions. 24 (7): 590–598. doi:10.1111/ajad.12291. ISSN   1055-0496. PMID   26346395.
  27. Irish, Leah A.; Kline, Christopher E.; Gunn, Heather E.; Buysse, Daniel J.; Hall, Martica H. (2015). "The role of sleep hygiene in promoting public health: A review of empirical evidence". Sleep Medicine Reviews. 22: 23–36. doi:10.1016/j.smrv.2014.10.001. ISSN   1087-0792. PMC   4400203 . PMID   25454674.
  28. 1 2 SGUS 2016, p. 5; Chapter 1.
  29. 1 2 Collaco, Joseph M.; McGrath-Morrow, Sharon A. (2018). "Electronic Cigarettes: Exposure and Use Among Pediatric Populations". Journal of Aerosol Medicine and Pulmonary Drug Delivery. 31 (2): 71–77. doi:10.1089/jamp.2017.1418. ISSN   1941-2711. PMC   5915214 . PMID   29068754.
  30. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Electronic Cigarettes (E-cigarettes)". National Institute on Drug Abuse. March 2018.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  31. 1 2 3 4 5 SGUS 2016, p. 186; Chapter 5.
  32. Kaisar, Mohammad Abul; Prasad, Shikha; Liles, Tylor; Cucullo, Luca (2016). "A Decade of e-Cigarettes: Limited Research & Unresolved Safety Concerns". Toxicology. 365: 67–75. doi:10.1016/j.tox.2016.07.020. ISSN   0300-483X. PMC   4993660 . PMID   27477296.
  33. Weaver, Michael; Breland, Alison; Spindle, Tory; Eissenberg, Thomas (2014). "Electronic Cigarettes". Journal of Addiction Medicine. 8 (4): 234–240. doi:10.1097/ADM.0000000000000043. ISSN   1932-0620. PMC   4123220 . PMID   25089953.
  34. 1 2 3 4 5 6 7 8 9 10 11 12 13 Jenssen, Brian P.; Boykan, Rachel (2019). "Electronic Cigarettes and Youth in the United States: A Call to Action (at the Local, National and Global Levels)". Children. 6 (2): 30. doi: 10.3390/children6020030 . ISSN   2227-9067. PMC   6406299 . PMID   30791645. Creative Commons by small.svg  This article incorporates text by Brian P. Jenssen and Rachel Boykan available under the CC BY 4.0 license.
  35. Kenny, PJ (September 2014). "Genetics of Substance Use Disorders". Dialogues Clin Neurosci. 16 (3): 335–344. doi:10.31887/DCNS.2014.16.3/pkenny. PMC   4214176 . PMID   25364284.
  36. D'Souza, Manoranjan S. (2015). "Glutamatergic transmission in drug reward: implications for drug addiction". Frontiers in Neuroscience. 9: 404. doi: 10.3389/fnins.2015.00404 . ISSN   1662-453X. PMC   4633516 . PMID   26594139.
  37. MacDonald, K; Pappa, K (April 2016). "WHY NOT POT?: A Review of the Brain-based Risks of Cannabis". Innov Clin Neurosci. 13 (3–4): 13–22. PMC   4911936 . PMID   27354924.
  38. Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro (2014). "Nicotine Effects and the Endogenous Opioid System". Journal of Pharmacological Sciences. 125 (2): 117–124. doi: 10.1254/jphs.14R03CP . ISSN   1347-8613. PMID   24882143.
  39. Lee, Peter N.; Fariss, Marc W. (2016). "A systematic review of possible serious adverse health effects of nicotine replacement therapy". Archives of Toxicology. 91 (4): 1565–1594. doi:10.1007/s00204-016-1856-y. ISSN   0340-5761. PMC   5364244 . PMID   27699443.
  40. D'Souza MS, Markou A (2011). "Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments". Addict Sci Clin Pract. 6 (1): 4–16. PMC   3188825 . PMID   22003417.
  41. 1 2 3 Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I. (2015). "New mechanisms and perspectives in nicotine withdrawal". Neuropharmacology. 96 (Pt B): 223–234. doi:10.1016/j.neuropharm.2014.11.009. ISSN   0028-3908. PMC   4444410 . PMID   25433149.
  42. Besson, Morgane; Forget, Benoît (2016). "Cognitive Dysfunction, Affective States, and Vulnerability to Nicotine Addiction: A Multifactorial Perspective". Frontiers in Psychiatry. 7: 160. doi: 10.3389/fpsyt.2016.00160 . ISSN   1664-0640. PMC   5030478 . PMID   27708591. Creative Commons by small.svg  This article incorporates text by Morgane Besson and Benoît Forget available under the CC BY 4.0 license.
  43. Hadjiconstantinou, Maria; Neff, Norton H. (2011). "Nicotine and endogenous opioids: Neurochemical and pharmacological evidence". Neuropharmacology. 60 (7–8): 1209–1220. doi:10.1016/j.neuropharm.2010.11.010. ISSN   0028-3908. PMID   21108953. S2CID   45539554.
  44. 1 2 3 4 Korpi, E. R.; den Hollander, B.; Farooq, U.; Vashchinkina, E.; Rajkumar, R.; Nutt, D. J.; Hyytia, P.; Dawe, G. S. (2015). "Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse". Pharmacological Reviews. 67 (4): 872–1004. doi: 10.1124/pr.115.010967 . ISSN   1521-0081. PMID   26403687. S2CID   24802846.
  45. Yu, Cassie; McClellan, Jon (2016). "Genetics of Substance Use Disorders". Child and Adolescent Psychiatric Clinics of North America. 25 (3): 377–385. doi:10.1016/j.chc.2016.02.002. ISSN   1056-4993. PMID   27338962.
  46. 1 2 Wen, L; Yang, Z; Cui, W; Li, M D (2016). "Crucial roles of the CHRNB3–CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research". Translational Psychiatry. 6 (6): e843. doi:10.1038/tp.2016.103. ISSN   2158-3188. PMC   4931601 . PMID   27327258.
  47. 1 2 Chen, Li-Shiun; Horton, Amy; Bierut, Laura (2016). "Pathways to precision medicine in smoking cessation treatments". Neuroscience Letters. 669: 83–92. doi:10.1016/j.neulet.2016.05.033. ISSN   0304-3940. PMC   5115988 . PMID   27208830.
  48. Chenoweth, Meghan J.; Tyndale, Rachel F. (2017). "Pharmacogenetic Optimization of Smoking Cessation Treatment". Trends in Pharmacological Sciences. 38 (1): 55–66. doi:10.1016/j.tips.2016.09.006. ISSN   0165-6147. PMC   5195866 . PMID   27712845.
  49. 1 2 3 Baraona, L. Kim; Lovelace, Dawn; Daniels, Julie L.; McDaniel, Linda (2017). "Tobacco Harms, Nicotine Pharmacology, and Pharmacologic Tobacco Cessation Interventions for Women". Journal of Midwifery & Women's Health. 62 (3): 253–269. doi:10.1111/jmwh.12616. ISSN   1526-9523. PMID   28556464. S2CID   1267977.
  50. Di Matteo, Vincenzo; Pierucci, Massimo; Di Giovanni, Giuseppe; Benigno, Arcangelo; Esposito, Ennio (2007). "The Neurobiological Bases for the Pharmacotherapy of Nicotine Addiction". Current Pharmaceutical Design. 13 (12): 1269–1284. doi:10.2174/138161207780618920. ISSN   1381-6128. PMID   17504235.
  51. "Know The Risks: E-Cigarettes & Young People – Addiction". Surgeon General of the United States. 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  52. Atta-ur- Rahman; Allen B. Reitz (1 January 2005). Frontiers in Medicinal Chemistry. Bentham Science Publishers. pp. 279–. ISBN   978-1-60805-205-9.
  53. Bruijnzeel, Adrie W. (2012). "Tobacco addiction and the dysregulation of brain stress systems". Neuroscience & Biobehavioral Reviews. 36 (5): 1418–1441. doi:10.1016/j.neubiorev.2012.02.015. ISSN   0149-7634. PMC   3340450 . PMID   22405889.
  54. Alasmari, Fawaz; Al-Rejaie, Salim S.; AlSharari, Shakir D.; Sari, Youssef (2016). "Targeting glutamate homeostasis for potential treatment of nicotine dependence". Brain Research Bulletin. 121: 1–8. doi:10.1016/j.brainresbull.2015.11.010. ISSN   0361-9230. PMC   4783195 . PMID   26589642.
  55. 1 2 Uchida, Sae; Hotta, Harumi (2009). "Cerebral Cortical Vasodilatation Mediated by Nicotinic Cholinergic Receptors: Effects of Old Age and of Chronic Nicotine Exposure". Biological & Pharmaceutical Bulletin. 32 (3): 341–344. doi: 10.1248/bpb.32.341 . ISSN   0918-6158. PMID   19252275.
  56. SGUS 2014, p. 111.
  57. Dineley, Kelly T.; Pandya, Anshul A.; Yakel, Jerrel L. (2015). "Nicotinic ACh receptors as therapeutic targets in CNS disorders". Trends in Pharmacological Sciences. 36 (2): 96–108. doi:10.1016/j.tips.2014.12.002. ISSN   0165-6147. PMC   4324614 . PMID   25639674.
  58. Caponnetto, P.; Russo, C.; Bruno, C.M.; Alamo, A.; Amaradio, M.D.; Polosa, R. (March 2013). "Electronic cigarette: a possible substitute for cigarette dependence". Monaldi Archives for Chest Disease. 79 (1): 12–19. doi: 10.4081/monaldi.2013.104 . ISSN   1122-0643. PMID   23741941.
  59. 1 2 Rowell, Temperance R; Tarran, Robert (2015). "Will Chronic E-Cigarette Use Cause Lung Disease?". American Journal of Physiology. Lung Cellular and Molecular Physiology. 309 (12): L1398–409. doi:10.1152/ajplung.00272.2015. ISSN   1040-0605. PMC   4683316 . PMID   26408554.
  60. 1 2 Engel, Jörgen A.; Jerlhag, Elisabet (2014). "Role of Appetite-Regulating Peptides in the Pathophysiology of Addiction: Implications for Pharmacotherapy". CNS Drugs. 28 (10): 875–886. doi:10.1007/s40263-014-0178-y. ISSN   1172-7047. PMC   4181507 . PMID   24958205.
  61. "Nicotine and Tobacco". A.D.A.M. Medical Encyclopedia. Medline Plus. 7 June 2016.
  62. Khoudigian, S.; Devji, T.; Lytvyn, L.; Campbell, K.; Hopkins, R.; O'Reilly, D. (29 January 2016). "The efficacy and short-term effects of electronic cigarettes as a method for smoking cessation: a systematic review and a meta-analysis". International Journal of Public Health. 61 (2): 257–267. doi:10.1007/s00038-016-0786-z. ISSN   1661-8556. PMID   26825455. S2CID   22227035.
  63. 1 2 "Nicotine". National Institute on Drug Abuse. June 2007. Archived from the original on 2019-06-11. Retrieved 2019-09-07.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  64. Shahab, Lion; Brose, Leonie S.; West, Robert (2013). "Novel Delivery Systems for Nicotine Replacement Therapy as an Aid to Smoking Cessation and for Harm Reduction: Rationale, and Evidence for Advantages over Existing Systems". CNS Drugs. 27 (12): 1007–1019. doi:10.1007/s40263-013-0116-4. ISSN   1172-7047. PMID   24114587. S2CID   207486096.
  65. Vanker, A.; Gie, R.P.; Zar, H.J. (2017). "The Association Between Environmental Tobacco Smoke Exposure and Childhood Respiratory Disease: A Review". Expert Review of Respiratory Medicine. 11 (8): 661–673. doi:10.1080/17476348.2017.1338949. ISSN   1747-6348. PMC   6176766 . PMID   28580865.
  66. Palazzolo, Dominic L. (November 2013). "Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review". Frontiers in Public Health. 1 (56): 56. doi: 10.3389/fpubh.2013.00056 . PMC   3859972 . PMID   24350225.
  67. 1 2 Schroeder, M. J.; Hoffman, A. C. (2014). "Electronic cigarettes and nicotine clinical pharmacology". Tobacco Control. 23 (Supplement 2): ii30–ii35. doi:10.1136/tobaccocontrol-2013-051469. ISSN   0964-4563. PMC   3995273 . PMID   24732160.
  68. Bold, Krysten W.; Sussman, Steve; O'Malley, Stephanie S.; Grana, Rachel; Foulds, Jonathan; Fishbein, Howard; Krishnan-Sarin, Suchitra (2017). "Measuring E-cigarette dependence: Initial guidance". Addictive Behaviors. 79: 213–218. doi:10.1016/j.addbeh.2017.11.015. ISSN   0306-4603. PMC   5807200 . PMID   29174664.
  69. Breland, Alison B.; Spindle, Tory; Weaver, Michael; Eissenberg, Thomas (2014). "Science and Electronic Cigarettes". Journal of Addiction Medicine. 8 (4): 223–233. doi:10.1097/ADM.0000000000000049. ISSN   1932-0620. PMC   4122311 . PMID   25089952.
  70. McNeill 2018, p. 12.
  71. 1 2 Cullen, Karen A.; Ambrose, Bridget K.; Gentzke, Andrea S.; Apelberg, Benjamin J.; Jamal, Ahmed; King, Brian A. (2018). "Notes from the Field: Use of Electronic Cigarettes and Any Tobacco Product Among Middle and High School Students — United States, 2011–2018". MMWR. Morbidity and Mortality Weekly Report. 67 (45): 1276–1277. doi:10.15585/mmwr.mm6745a5. ISSN   0149-2195. PMC   6290807 . PMID   30439875.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  72. "THE FACTS on e-cigarette use among youth and young adults". Surgeon General of the United States. 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  73. Bhatnagar, A.; Whitsel, L. P.; Ribisl, K. M.; Bullen, C.; Chaloupka, F.; Piano, M. R.; Robertson, R. M.; McAuley, T.; Goff, D.; Benowitz, N. (24 August 2014). "Electronic Cigarettes: A Policy Statement From the American Heart Association". Circulation. 130 (16): 1418–1436. doi:10.1161/CIR.0000000000000107. PMC   7643636 . PMID   25156991. S2CID   16075813.
  74. Hildick-Smith, Gordon J.; Pesko, Michael F.; Shearer, Lee; Hughes, Jenna M.; Chang, Jane; Loughlin, Gerald M.; Ipp, Lisa S. (2015). "A Practitioner's Guide to Electronic Cigarettes in the Adolescent Population". Journal of Adolescent Health. 57 (6): 574–9. doi: 10.1016/j.jadohealth.2015.07.020 . ISSN   1054-139X. PMID   26422289.
  75. WHO 2014, p. 6.
  76. 1 2 3 4 Chapman 2015, p. 5.
  77. 1 2 Schraufnagel DE (2015). "Electronic Cigarettes: Vulnerability of Youth". Pediatr Allergy Immunol Pulmonol. 28 (1): 2–6. doi:10.1089/ped.2015.0490. PMC   4359356 . PMID   25830075.
  78. "Teens like different forms of tobacco and nicotine". American Cancer Society. Archived from the original on 20 September 2015.
  79. 1 2 Singh, Tushar; Arrazola, René A.; Corey, Catherine G.; Husten, Corinne G.; Neff, Linda J.; Homa, David M.; King, Brian A. (2016). "Tobacco Use Among Middle and High School Students — United States, 2011–2015". MMWR. Morbidity and Mortality Weekly Report. 65 (14): 361–367. doi: 10.15585/mmwr.mm6514a1 . ISSN   0149-2195. PMID   27077789.
  80. Chatterjee, Kshitij; Alzghoul, Bashar; Innabi, Ayoub; Meena, Nikhil (2016). "Is vaping a gateway to smoking: a review of the longitudinal studies". International Journal of Adolescent Medicine and Health. 30 (3). doi:10.1515/ijamh-2016-0033. ISSN   2191-0278. PMID   27505084. S2CID   23977146.
  81. Dinakar, Chitra; Longo, Dan L.; O'Connor, George T. (2016). "The Health Effects of Electronic Cigarettes". New England Journal of Medicine. 375 (14): 1372–1381. doi:10.1056/NEJMra1502466. ISSN   0028-4793. PMID   27705269.
  82. SGUS 2016, p. 102; Chapter 3.
  83. Soneji, Samir; Barrington-Trimis, Jessica L.; Wills, Thomas A.; Leventhal, Adam M.; Unger, Jennifer B.; Gibson, Laura A.; Yang, JaeWon; Primack, Brian A.; Andrews, Judy A.; Miech, Richard A.; Spindle, Tory R.; Dick, Danielle M.; Eissenberg, Thomas; Hornik, Robert C.; Dang, Rui; Sargent, James D. (2017). "Association Between Initial Use of e-Cigarettes and Subsequent Cigarette Smoking Among Adolescents and Young Adults". JAMA Pediatrics. 171 (8): 788–797. doi:10.1001/jamapediatrics.2017.1488. ISSN   2168-6203. PMC   5656237 . PMID   28654986.
  84. Kamat, Aarti D.; Van Dyke, Alison L. (2017). "Use of Electronic Nicotine Delivery Systems Among Adolescents: Status of the Evidence and Public Health Recommendations". Pediatric Annals. 46 (2): e69–e77. doi:10.3928/19382359-20170111-01. ISSN   1938-2359. PMID   28192582. S2CID   20909216.
  85. "Position Statement on Electronic Cigarettes [ECs] or Electronic Nicotine Delivery Systems [ENDS]" (PDF). The International Union against Tuberculosis and Lung Disease. October 2013. Archived from the original (PDF) on 2016-03-05. Retrieved 2019-09-07.
  86. Korioth, Trisha (4 October 2013). "E-cigarettes easy to buy, can hook kids on nicotine". AAP News: E131004-4. doi:10.1542/aapnews.20133411-24d (inactive 31 January 2024).{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
  87. Stacy Simon (17 April 2015). "E-Cigarette Use Triples Among Middle and High School Students". American Cancer Society.
  88. "FDA Warns of Health Risks Posed by E-Cigarettes". United States Food and Drug Administration . 17 September 2013. Reviewed 17 September 2013
  89. Durmowicz, E. L. (2014). "The impact of electronic cigarettes on the paediatric population". Tobacco Control. 23 (Supplement 2): ii41–ii46. doi:10.1136/tobaccocontrol-2013-051468. ISSN   0964-4563. PMC   3995262 . PMID   24732163.
  90. 1 2 3 4 5 6 7 England, Lucinda J.; Aagaard, Kjersti; Bloch, Michele; Conway, Kevin; Cosgrove, Kelly; Grana, Rachel; Gould, Thomas J.; Hatsukami, Dorothy; Jensen, Frances; Kandel, Denise; Lanphear, Bruce; Leslie, Frances; Pauly, James R.; Neiderhiser, Jenae; Rubinstein, Mark; Slotkin, Theodore A.; Spindel, Eliot; Stroud, Laura; Wakschlag, Lauren (2017). "Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products". Neuroscience & Biobehavioral Reviews. 72: 176–189. doi:10.1016/j.neubiorev.2016.11.013. ISSN   0149-7634. PMC   5965681 . PMID   27890689.
  91. WHO 2014, p. 9.
  92. "Know The Risks: E-Cigarettes & Young People – Use of Two or More Tobacco Products". Surgeon General of the United States. 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  93. SGUS 2016, p. 107; Chapter 3.
  94. 1 2 3 4 5 6 7 SGUS 2016, p. 105; Chapter 3.
  95. Greenhill, Richard; Dawkins, Lynne; Notley, Caitlin; Finn, Mark D.; Turner, John J.D. (2016). "Adolescent Awareness and Use of Electronic Cigarettes: A Review of Emerging Trends and Findings". Journal of Adolescent Health. 59 (6): 612–619. doi: 10.1016/j.jadohealth.2016.08.005 . ISSN   1054-139X. PMID   27693128.
  96. "WHO Right to Call for E-Cigarette Regulation". World Lung Federation. 26 August 2014.
  97. 1 2 Chapman 2015, p. 6.
  98. 1 2 3 Modesto-Lowe, Vania; Alvarado, Camille (2017). "E-cigs . . . Are They Cool? Talking to Teens About E-Cigarettes". Clinical Pediatrics. 56 (10): 947–952. doi:10.1177/0009922817705188. ISSN   0009-9228. PMID   28443340. S2CID   44423931.
  99. Wolff, Mary S.; Buckley, Jessie P.; Engel, Stephanie M.; McConnell, Rob S.; Barr, Dana B. (2017). "Emerging exposures of developmental toxicants". Current Opinion in Pediatrics. 29 (2): 218–224. doi:10.1097/MOP.0000000000000455. ISSN   1040-8703. PMC   5473289 . PMID   28059904.
  100. Tobore, Tobore Onojighofia (2019). "On the potential harmful effects of E-Cigarettes (EC) on the developing brain: The relationship between vaping-induced oxidative stress and adolescent/young adults social maladjustment". Journal of Adolescence. 76: 202–209. doi:10.1016/j.adolescence.2019.09.004. ISSN   0140-1971. PMID   31574388. S2CID   203640780.
  101. "Some E-cigarette Users Are Having Seizures, Most Reports Involving Youth and Young Adults". United States Food and Drug Administration. 3 April 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  102. Smith, L; Brar, K; Srinivasan, K; Enja, M; Lippmann, S (June 2016). "E-cigarettes: How "safe" are they?". J Fam Pract. 65 (6): 380–5. PMID   27474819.
  103. 1 2 3 Lødrup Carlsen, Karin C.; Skjerven, Håvard O.; Carlsen, Kai-Håkon (2018). "The toxicity of E-cigarettes and children's respiratory health". Paediatric Respiratory Reviews. 28: 63–67. doi:10.1016/j.prrv.2018.01.002. ISSN   1526-0542. PMID   29580719. S2CID   4368058.
  104. 1 2 3 4 5 6 7 8 9 Holbrook, Bradley D. (2016). "The effects of nicotine on human fetal development". Birth Defects Research Part C: Embryo Today: Reviews. 108 (2): 181–192. doi:10.1002/bdrc.21128. ISSN   1542-975X. PMID   27297020.
  105. 1 2 3 Makadia, Luv D.; Roper, P. Jervey; Andrews, Jeannette O.; Tingen, Martha S. (2017). "Tobacco Use and Smoke Exposure in Children: New Trends, Harm, and Strategies to Improve Health Outcomes". Current Allergy and Asthma Reports. 17 (8): 55. doi:10.1007/s11882-017-0723-0. ISSN   1529-7322. PMID   28741144. S2CID   22360961.
  106. 1 2 3 Behnke, M.; Smith, V. C. (2013). "Prenatal Substance Abuse: Short- and Long-term Effects on the Exposed Fetus". Pediatrics. 131 (3): e1009–e1024. doi: 10.1542/peds.2012-3931 . ISSN   0031-4005. PMC   8194464 . PMID   23439891. S2CID   135162.
  107. 1 2 Kohlmeier, K. A. (2015). "Nicotine during pregnancy: changes induced in neurotransmission, which could heighten proclivity to addict and induce maladaptive control of attention". Journal of Developmental Origins of Health and Disease. 6 (3): 169–181. doi:10.1017/S2040174414000531. ISSN   2040-1744. PMID   25385318. S2CID   29298949.
  108. 1 2 Alkam, Tursun; Nabeshima, Toshitaka (2019). "Molecular mechanisms for nicotine intoxication". Neurochemistry International. 125: 117–126. doi:10.1016/j.neuint.2019.02.006. ISSN   0197-0186. PMID   30779928. S2CID   72334402.
  109. SGUS 2016, p. vii; Preface.
  110. Drummond, MB; Upson, D (February 2014). "Electronic cigarettes. Potential harms and benefits". Annals of the American Thoracic Society. 11 (2): 236–42. doi:10.1513/annalsats.201311-391fr. PMC   5469426 . PMID   24575993.
  111. "Electronic Nicotine Delivery Systems (ENDS), including E-cigarettes". New Zealand Ministry of Health. 2014. Archived from the original on 2015-05-11.
  112. "Electronic Cigarettes – An Overview" (PDF). German Cancer Research Center. 2013.
  113. 1 2 Li, Gerard; Saad, Sonia; Oliver, Brian; Chen, Hui (2018). "Heat or Burn? Impacts of Intrauterine Tobacco Smoke and E-Cigarette Vapor Exposure on the Offspring's Health Outcome". Toxics. 6 (3): 43. doi: 10.3390/toxics6030043 . ISSN   2305-6304. PMC   6160993 . PMID   30071638. Creative Commons by small.svg  This article incorporates text by Gerard Li, Sonia Saad, Brian G. Oliver, and Hui Chen available under the CC BY 4.0 license.
  114. "Electronic Cigarettes – What are the health effects of using e-cigarettes?" (PDF). Centers for Disease Control and Prevention. 22 February 2018.
  115. 1 2 Greene, Robert M.; Pisano, M. Michele (2019). "Developmental toxicity of e-cigarette aerosols". Birth Defects Research. 111 (17): 1294–1301. doi:10.1002/bdr2.1571. ISSN   2472-1727. PMID   31400084. S2CID   199518879.