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Smoking makes the brain operate slower that normal

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Smoking can cause heart disease within a month of smoking.

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Smoking damages nearly every organ in the body. People can significantly reduce their chance of smoking-related disease by giving it up.

Smoking is the leading preventable cause of early disease and death in the United States. Giving up smoking is difficult for many people, but the number of former smokers is increasing all the time.

According to the Centers for Disease Control and Prevention (CDC), current smoking in the U.S. has declined from 20.9% in 2005 to 13.7% in 2018. The number of smokers who have quit is also rising.

In this article, we look at the health impact of smoking, including its effects on the brain, heart, lungs, and immune system. We also discuss the benefits of quitting.

Every year, more than 480,000 people die in the U.S. due to tobacco-related diseases - around 1 in 5 of all deaths - according to the American Cancer Society.

They also state that around half of people in the U.S. who keep smoking will die from smoking-related causes.

Life expectancy is at least 10 years less for smokers compared with nonsmokers. The American Cancer Society state that smoking shortens lifespan by about 12 years in males and 11 years in females.

The comment that smoking causes more deaths in the U.S. each year than the following combined:

motor vehicle injuries

alcohol or illicit drug use

firearm-related incidents

Tobacco contains poisonous substances that affect people's health. Two of these poisons are:

Carbon monoxide. Car exhaust fumes also produce this substance, and it is fatal in large doses. It replaces oxygen in the blood and starves the organs of oxygen, stopping them from functioning correctly.

Tar. This is a sticky, brown substance that coats the lungs and affects breathing.

While the statistics are alarming, it is important to bear in mind that giving up smoking reduces the risk of disease dramatically.

Below, we discuss the impact smoking can have on different parts of the body.

Smoking can increase the likelihood of having a stroke by . Strokes can cause brain damage and death.

One way that stroke can cause brain injury is through a brain aneurysm, which occurs when the wall of a blood vessel weakens and creates a bulge. This bulge can burst and cause a subarachnoid hemorrhage, which can lead to a stroke.

Chemicals in tobacco smoke increase the chance of heart problems and cardiovascular diseases.

Smoking causes atherosclerosis, which is when plaque builds up in the blood and sticks to the artery walls. This makes them narrower, reducing blood flow and increasing the risk of blood clots.

Smoking also damages the blood vessels, making them thicker and narrower. This makes it harder for blood to flow, and also increases blood pressure and heart rate.

Smoking has links with the following cardiovascular conditions:

coronary heart disease, one of the leading causes of death in the U.S

a heart attack, as smoking doubles the risk of heart attack

blockages that reduce blood flow to the skin and legs

stroke due to blood clots or burst blood vessels in the brain

Even smokers who smoke cigarettes a day may develop early signs of cardiovascular disease.

Carbon monoxide and nicotine make the heart work harder and faster. This means that smoking makes it more challenging to exercise. A lack of exercise further increases the risk of health problems.

According to the National Institutes of Health (NIH), smoking reduces bone density, making the bones weaker and more brittle. Smoking can also impair bone healing after a fracture.

Researchers find it difficult to say whether this is a direct effect of smoking, or due to other risk factors prevalent in people who smoke. These include lower body weight and doing less physical exercise.

This may affect females than males. Females are more prone to osteoporosis and broken bones.

Quitting smoking, even later in life, can help limit bone loss linked with smoking.

The immune system protects the body against infection and disease.

According to one , smoking reduces immune function and causes inflammation in the body. This can lead to autoimmune conditions, including:

Smoking also has links with type 2 diabetes.

The lungs are perhaps the most obvious organ that smoking affects.

It often takes many years before a person notices any symptoms of smoking-related lung disease. This means that people may not receive a diagnosis until the disease is quite advanced.

Smoking can impact the lungs in several ways. The primary reason is that smoking damages the airways and air sacs - known as alveoli - in the lungs.

Three of the most common smoking-related lung conditions in the U.S. are:

Chronic obstructive pulmonary disease (COPD). COPD is a long-term disease. It causes wheezing, shortness of breath, and chest tightness. COPD is the third leading cause of death in the U.S.

Chronic bronchitis. Chronic bronchitis occurs when the airways produce too much mucus. This leads to a long-lasting cough and inflamed airways. Over time, scar tissue and mucus can completely block the airways and cause infection.

Emphysema: Emphysema is a type of COPD that reduces the number of alveoli and breaks down the walls between them. This makes it difficult to breathe, even at rest, and over time, a person may need an oxygen mask.

Other lung diseases caused by smoking include pneumonia, asthma, and tuberculosis.

Smoking can have several effects on oral health and may cause:

Smoking irritates the gum tissues. The American Dental Association (ADA) state that smoking increases the risk of gum disease, which can add to halitosis.

Smoking affect the reproductive system and fertility.

Females who smoke can have more difficulty becoming pregnant. In males, smoking can cause impotence by damaging blood vessels in the penis. It can also damage sperm and affect sperm count.

premature birth

pregnancy loss

low birth weight

sudden infant death syndrome

infant illnesses

According to some studies, males who smoke have a lower sperm count than those who do not.

Smoking while pregnant increases a number of risks for the baby, including:

facial wrinkles, especially around the lips

baggy eyelids

uneven skin coloring, such as a yellow or gray tone

dry, coarse skin

temporary yellowing of the fingers and fingernails

Smoking reduces the amount of oxygen that can reach the skin. This speeds up the aging process and can make skin appear dull or gray.

Smoking can cause:

Smoking reduces how quickly skin wounds heal, increases the risk of skin infections, and increases the severity of skin conditions, including psoriasis.

Smoking increases the risk of many types of cancer. According to the National Cancer Institute, tobacco smoke contains around 7,000 chemicals, of which at least 69 can cause cancer.

Figures from the American Cancer Society state that smoking causes around 30% of all cancer deaths in the U.S., and 80% of all lung cancer deaths.

Lung cancer is the leading cause of cancer death in both men and women. It is one of the most difficult to treat.
Read more about how smoking affects the body here.
Smoking is a risk factor for the following cancers:

Cigars, pipe-smoking, menthol cigarettes, chewing tobacco, and other forms of tobacco all cause cancer and other health problems. There is no safe way to use tobacco.

While the statistics are alarming, the good news is that quitting smoking reduces the risk of disease and death significantly. The risks drop further, the longer a person refrains from smoking.

Cardiovascular risks: After 1 year of quitting, the risk of having a heart attack drops sharply.

Stroke: Within 2-5 years, the risk of a stroke reduces to half that of a non-smoker.

Cancers: The risks for mouth, throat, esophagus, and bladder cancer drop by half within 5 years of quitting, and 10 years for lung cancer.

In fact, some research says that quitting before the age of 40 reduces the risk of dying from smoking-related disease by about 90%.

breathing becomes easier

daily coughing and wheezing reduces then disappears

sense of taste and smell get better

exercise and activities become easier

circulation to the hands and feet improves

Read more about what happens when you quit smoking here.
These statistics illustrate the health benefits of quitting smoking:

Soon after quitting, people experience the following health benefits that can significantly improve their quality of life and serve as reminders of the health benefits that quitting can have:

Though quitting can be stressful, people often start to notice their daily stress levels are much lower than when they were smoking within 6 months or so.

Make lists of reasons why it is a good idea to quit. Read over these when the temptation to smoke strikes.

Use an app to track your progress. Reaching milestones, such as a day without smoking, can help motivate a person to continue. There are many free and paid apps on the market.

Try nicotine replacement products. Nicotine patches, gums, and lozenges can help reduce cravings, making it easier to resist at any particular moment.

Quitting smoking is a different journey for everyone, and what works for one person will not always work for the next. Try out a few different ways to see which ones work best.

When trying to quit smoking, these tips may help:

Many people find that reaching out to a healthcare provider for support can help them quit for good. A doctor can prescribe medication, such as varenicline (Chantix). currently recommend this as a first-line therapy for people who want to quit smoking.

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Smoking damages nearly every organ in the body. People can significantly reduce their chance of smoking-related disease by giving it up. Smoking is the leading preventable cause of early disease and death in the United States. Giving up smoking is difficult for many people, but the number of former smokers is increasing all the time.

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Smoking can cause emphyasema from a young age.

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Neal L. Benowitz, M.D.

Cigarette smoking remains a leading cause of preventable disease and premature death in the United States and other countries. On average, 435,000 people in the United States die prematurely from smoking-related diseases each year; overall, smoking causes 1 in 5 deaths. The chance that a lifelong smoker will die prematurely from a complication of smoking is approximately 50%.

Tobacco use is a major cause of death from cancer, cardiovascular disease, and pulmonary disease. Cigarette smoking is also a risk factor for respiratory tract and other infections, osteoporosis, reproductive disorders, adverse postoperative events and delayed wound healing, duodenal and gastric ulcers, and diabetes. In addition, smoking has a strong association with fire-related and trauma-related injuries. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke. Although nicotine plays a minor role, if any, in causing smoking-induced diseases, addiction to nicotine is the proximate cause of these diseases.

Currently, about 45 million Americans smoke tobacco. Seventy percent of smokers say they would like to quit, and every year, 40% do quit for at least 1 day. Some highly addicted smokers make serious attempts to quit but are able to stop only for a few hours. Moreover, the 80% who attempt to quit on their own return to smoking within a month, and each year, only 3% of smokers quit successfully. Unfortunately, the rate at which persons - primarily children and adolescents - become daily smokers nearly matches the quit rate, so the prevalence of cigarette smoking has declined only very slowly in recent years.

This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. Tobacco addiction (like all drug addictions) involves the interplay of pharmacology, learned or conditioned factors, genetics, and social and environmental factors (including tobacco product design and marketing) (). The pharmacologic reasons for nicotine use are enhancement of mood, either directly or through relief of withdrawal symptoms, and augmentation of mental or physical functions.

BRAIN MECHANISMS

NICOTINIC ACETYLCHOLINE RECEPTORS

Inhalation of smoke from a cigarette distills nicotine from the tobacco in the cigarette. Smoke particles carry the nicotine into the lungs, where it is rapidly absorbed into the pulmonary venous circulation. The nicotine then enters the arterial circulation and moves quickly from the lungs to the brain, where it binds to nicotinic cholinergic receptors (ligand-gated ion channels that normally bind acetylcholine). The binding of nicotine at the interface between two subunits of the receptor opens the channel, thereby allowing the entry of sodium or calcium. The entry of these cations into the cell further activates voltage-dependent calcium channels, allowing more calcium to enter. One of the effects of the entry of calcium into a neuron is the release of neurotransmitters.

The nicotinic cholinergic receptor consists of five subunits. The mammalian brain expresses nine α subunits ( α ₂ through α ₁₀) and three β subunits ( β ₂ through β ₄). The most abundant receptors are α ₄ β ₂, α ₃ β ₄, and α ₇, the latter of which are homomeric. The α ₄ β ₂* receptor (the asterisk indicates that other subunits may be present in this receptor) is the principal mediator of nicotine dependence. In mice, disruption of the β ₂ subunit gene eliminates the behavioral effects of nicotine; reinserting the gene into the ventral tegmental area restores behavioral responses to nicotine., The α ₄ subunit is an important determinant of sensitivity to nicotine. A mutation affecting a single nucleotide in the pore-forming region of the mouse receptor gene makes it hypersensitive to the effects of nicotine. Other subunits can form functional receptors. The presence of an α ₅ subunit combined with α ₄ β ₂ increases calcium conductance seven times; α ₅ gene variants also alter nicotine responsiveness in cultured human cells., The α ₃ β ₄ subtype probably mediates the cardiovascular effects of nicotine. The α ₇ homomeric receptors are involved in rapid synaptic transmission and long-term potentiation to dopaminergic neurons at excitatory inputs and have a role in learning and sensory gating. ⁻

NICOTINE AND NEUROTRANSMITTER RELEASE

Stimulation of nicotinic cholinergic receptors releases a variety of neurotransmitters in the brain., One of them, dopamine, signals a pleasurable experience and is critical for the reinforcing effects (effects that promote self-administration) of nicotine and other drugs of abuse, as well as for compelling drives such as eating. Experimentally induced lesions in dopamine-releasing neurons prevent self-administration of nicotine in rats. Nicotine releases dopamine in the mesolimbic area, the corpus striatum, and the frontal cortex (). The dopaminergic neurons in the ventral tegmental area of the midbrain and in the shell of the nucleus accumbens are critical in drug-induced reward (both regions have a role in perceptions of pleasure and reward).,

Nicotine also augments both glutamate release, which facilitates the release of dopamine, and γ-aminobutyric acid (GABA) release, which inhibits dopamine release., With long-term exposure to nicotine, some nicotinic cholinergic receptors become desensitized but some do not. As a result, GABA-mediated inhibitory tone diminishes while glutamate-mediated excitation persists, thereby increasing excitation of dopaminergic neurons and enhancing responsiveness to nicotine.

A measure of the function of the reward system in rats is the threshold for electrical self-stimulation in the medial forebrain: a lower threshold indicates increased responsiveness to rewarding stimuli. Nicotine lowers the threshold for reward, an effect that can last for more than 30 days. It also increases activity in the prefrontal cortex, thalamus, and visual system, reflecting activation of corticobasal ganglia-thalamic brain circuits (part of the reward network), and releases dopamine in the striatum. Other neurotransmitters that may be involved in nicotine addiction are the hypocretins, neuropeptides produced in the lateral hypothalamus that regulate the stimulatory effects of nicotine on reward centers in the brain and modulate self-administration of nicotine in rodents.

MONAMINE OXIDASE

Constituents of cigarette smoke other than nicotine contribute to nicotine addiction. Monoamine oxidases, enzymes located in catecholaminergic and other neurons, catalyze the metabolism of dopamine, norepinephrine, and serotonin. Condensation products of acetaldehyde in cigarette smoke with biogenic amines inhibit the activity of monoamine oxidase type A and monoamine oxidase type B, and there is evidence that inhibition of monoamine oxidase contributes to the addictiveness of smoking by reducing the metabolism of dopamine.,

NEUROADAPTATION

With repeated exposure to nicotine, neuroadaptation (tolerance) to some of the effects of nicotine develops. As neuroadaptation develops, the number of binding sites on the nicotinic cholinergic receptors in the brain increases, probably in response to nicotine-mediated desensitization of receptors. Desensitization - ligand-induced closure and unresponsiveness of the receptor - is believed to play a role in tolerance and dependence: the symptoms of craving and withdrawal begin in smokers when desensitized α ₄ β ₂* nicotinic cholinergic receptors become responsive during periods of abstinence, such as nighttime sleep. Nicotine binding of these receptors during smoking alleviates craving and withdrawal.

Cigarette smoking in amounts that are typical for daily smokers maintains near-complete saturation - and thus desensitization - of the α ₄ β ₂* nicotinic cholinergic receptors. Thus, smokers are probably attempting to avoid withdrawal symptoms when maintaining a desensitized state. By sustaining sufficient levels of plasma nicotine to prevent withdrawal symptoms, they also derive rewarding effects from the conditioned reinforcements associated with smoking, such as the taste and feel of smoke.

Nicotine withdrawal causes anxiety and stress, both of which are powerful incentives to take up smoking again. The negative affect that typifies the response to nicotine withdrawal probably results in part from a cascade of events involving increased levels of extrahypothalamic corticotropin-releasing factor (CRF) and increased binding of CRF to corticotropin-releasing factor 1 (CRF1) receptors in the brain, thereby activating the CRF-CRF1 receptor system, which mediates responses to stress. In rats, anxiety-like behavior and the release of CRF in the central nucleus of the amygdala occur during nicotine withdrawal. CRF causes anxiety, whereas the pharmacologic blockade of CRF1 receptors inhibits the anxiogenic effects of nicotine withdrawal. The blockade of CRF1 receptors also prevents the increase in self-administration of nicotine that occurs during abstinence from forced nicotine administration in rats. Thus, both underactivity of the dopaminergic system and activation of the CRF-CRF1 receptor system contribute to the symptoms of nicotine withdrawal that often precipitate relapse.

CLINICAL ASPECTS OF NICOTINE ADDICTION

PSYCHOACTIVE EFFECTS OF NICOTINE

Nicotine induces pleasure and reduces stress and anxiety. Smokers use it to modulate levels of arousal and to control mood. Smoking improves concentration, reaction time, and performance of certain tasks. Relief from withdrawal symptoms is probably the primary reason for this enhanced performance and heightened mood. Cessation of smoking causes the emergence of withdrawal symptoms: irritability, depressed mood, restlessness, and anxiety. The intensity of these mood disturbances is similar to that found in psychiatric outpatients. Anhedonia - the feeling that there is little pleasure in life - can also occur with withdrawal from nicotine, and from other drugs of abuse.

The basis of nicotine addiction is a combination of positive reinforcements, including enhancement of mood and avoidance of withdrawal symptoms (). In addition, conditioning has an important role in the development of tobacco addiction.

CONDITIONED BEHAVIOR

When a person who is addicted to nicotine stops smoking, the urge to resume is recurrent and persists long after withdrawal symptoms dissipate. With regular smoking, the smoker comes to associate specific moods, situations, or environmental factors - smoking-related cues - with the rewarding effects of nicotine. Typically, these cues trigger relapse.

The association between such cues and the anticipated effects of nicotine, and the resulting urge to use nicotine, constitute a form of conditioning. Studies in animals show that nicotine exposure causes changes in the protein expression of brain cells and in their synaptic connections - a process termed neural plasticity - which underlie conditioning., Nicotine also enhances behavioral responses to conditioned stimuli, which may contribute to compulsive smoking. Furthermore, studies in nicotine-dependent rats show that conditioned stimuli associated with nicotine withdrawal increase the magnitude of withdrawal through an elevation of the brain's reward threshold. Thus, cues associated with nicotine withdrawal can decrease the function of the brain's reward systems.

The desire to smoke is maintained, in part, by such conditioning. Smokers usually take a cigarette after a meal, with a cup of coffee or an alcoholic drink, or with friends who smoke. When repeated many times, such situations become a powerful cue for the urge to smoke. Aspects of smoking itself - the manipulation of smoking materials, or the taste, smell, or feel of smoke in the throat - also become associated with the pleasurable effects of smoking., Even unpleasant moods can become conditioned cues for smoking: a smoker may learn that not having a cigarette provokes irritability and that smoking one provides relief. After repeated experiences like this, a smoker can sense irritability from any source as a cue for smoking. Functional imaging studies have shown that exposure to drug-associated cues activates cortical regions of the brain, including the insula (a structure in the cortex associated with certain basic emotions). Smokers who sustain damage to the insula (e.g., brain trauma) are more likely to quit smoking soon after the injury, and to remain abstinent, and are less likely to have conscious urges to smoke than smokers with brain injury that does not affect the insula.

THE TOBACCO ADDICTION CYCLE

Smoking is a highly efficient form of drug administration. Inhaled nicotine enters the circulation rapidly through the lungs and moves into the brain within seconds. Rapid rates of absorption and entry into the brain cause a strongly felt "rush" and reinforce the effects of the drug. In animals, rapid administration of nicotine potentiates locomotor sensitization, which is linked to reward, and neuroplastic changes in the brain. The smoking process also provides rapid reinforcement and allows for precise dosing, making it possible for a smoker to obtain desired effects without toxicity. Unlike cigarettes, nicotine medications marketed to promote smoking cessation deliver nicotine slowly, and the risk of abuse is low. In addition to delivering nicotine to the brain quickly, cigarettes have been designed with additives and engineering features to enhance its addictiveness.

There is considerable peak-to-trough oscillation in blood levels of nicotine from cigarette to cigarette. Nevertheless, it accumulates in the body over the course of 6 to 9 hours of regular smoking and results in 24 hours of exposure. Arteriovenous differences in nicotine concentrations during cigarette smoking are substantial, with arterial levels up to 10 times as high as venous levels. The persistence of nicotine in the brain throughout the day and night changes the structure and function of nicotinic receptors, stimulating intracellular processes of neuroadaptation.

The pharmacologic basis of nicotine addiction is thus a combination of positive reinforcements, such as enhancement of mood and mental or physical functioning, and avoidance of withdrawal symptoms when nicotine is not available. shows a typical daily smoking cycle.

Smokers tend to take in the same amount of nicotine from day to day to achieve the desired effects. They adjust their smoking behavior to compensate for changes in the availability of nicotine (e.g., when switching from regular to low-yield cigarettes) to regulate the body's level of nicotine. Light smokers (those who smoke ≤5 cigarettes per day) and occasional smokers smoke primarily for the positive reinforcing effects of nicotine and have minimal or no withdrawal symptoms. They smoke primarily in association with particular activities (after eating a meal or while drinking alcohol), and are less likely to smoke in response to negative affect. Although withdrawal symptoms may not be prominent, many light and occasional smokers have difficulty quitting. Some of them have a high level of dependence, but with pharmacodynamics that differ from those in heavier smokers.

GENETICS OF NICOTINE ADDICTION

Studies in twins have shown a high degree of heritability of cigarette smoking (≥50%), including the level of dependence and the number of cigarettes smoked daily. These studies have also revealed the heritability of the particular symptoms that occur when a smoker stops smoking.

Numerous attempts have been made to identify genes underlying nicotine addiction. Such studies are problematic because multiple genes and environmental factors determine complex behavior, and the many different dependence phenotypes may have different genetic underpinnings. Candidate genes coding for nicotine-receptor subtypes, dopamine receptors and dopamine transporters, GABA receptors, opiate and cannabinoid receptors, and other types of receptors have been associated with different aspects of smoking behavior. Subsequent research, however, has not replicated many of the initial findings.

Recent genomewide association studies point to several promising genetic determinants of nicotine dependence. Bierut et al. compared the genomes of smokers who became dependent on nicotine with the genomes of smokers who did not. Signals from genomewide association studies guided a second-phase candidate-gene association study by Saccone et al. in which several strong genetic associations were uncovered. Most prominent were genes within the α ₅/ α ₃/ β ₄ nicotinic cholinergic receptor gene complex on chromosome 15. This and other genomewide association studies of tobacco addiction have also identified genes affecting cell adhesion and extracellular matrix molecules, which are common among various addictions. These findings are consistent with the idea that neural plasticity and learning are key determinants of individual differences in vulnerability to nicotine dependence and other drug addictions.

Variants associated with nicotine dependence in the α ₅/ α ₃/ β ₄ gene region (chromosome 15, 15q25) also have a significant association with the number of cigarettes smoked per day, plasma levels of cotinine (a biomarker of nicotine intake), urine levels of tobacco-smoke carcinogens, and the risks of smoking-related diseases.,⁻ The mechanisms of the associations between these variants and disease are probably related to the level of dependence and therefore the level of intake of tobacco-smoke toxins; however, nicotinic cholinergic receptors also modulate inflammatory responses, angiogenesis, and apoptosis, and thus account for additional mechanisms through which nicotine could affect the risk of disease.

VULNERABILITY TO ADDICTION

Tobacco use typically begins in childhood or adolescence - 80% of smokers begin smoking by 18 years of age. Although two thirds of young people try cigarette smoking, only 20 to 25% of them become dependent daily smokers, usually as adults., Risk factors for smoking in childhood or adolescence include peer and parental influences, behavioral problems (e.g., poor school performance), personality characteristics (rebelliousness, risk taking, depression, and anxiety), and genetic influences.

The risk of dependence increases when smoking begins early. Studies of the developing brain in animals suggest that nicotine can induce permanent changes that lead to addiction. Brain changes in adolescent rats exposed to nicotine are greater than those in exposed adult rats. Adolescent rats that have been exposed to nicotine have higher rates of nicotine self-administration as adults, which is consistent with the idea that early exposure to nicotine increases the severity of dependence.,

Tobacco addiction is highly prevalent among persons with mental illness or substance-abuse disorders., The mechanisms of this association are likely to include a shared genetic predisposition, the capacity of nicotine to alleviate some psychiatric symptoms, and the inhibitory effects of tobacco smoke on monoamine oxidase.,,

Smoking behavior in women is more strongly influenced by conditioned cues and negative affect; men are more likely to smoke in response to pharmacologic cues, regulating their intake of nicotine more precisely than women. On average, women metabolize nicotine more quickly than men, which may contribute to their increased susceptibility to nicotine addiction and may help to explain why, among smokers, it is more difficult for women to quit.

Insofar as smokers regulate their intake of nicotine to maintain particular levels throughout the day, those who metabolize nicotine rapidly take in more cigarette smoke per day than those who metabolize nicotine slowly. Nicotine is metabolized to cotinine primarily by the liver enzyme CYP2A6. Persons with a genetic basis for slow metabolism (those with variant CYP2A6 genes that are associated with reduced enzyme activity) smoke fewer cigarettes daily than persons with faster metabolism. The observation that the fraction of smokers with genetically slow metabolism in the population of smokers decreases with the increasing age of the cohort of smokers suggests that those with slow metabolism are more likely to quit than those with faster metabolism. Rapid metabolism of nicotine is associated with more severe withdrawal symptoms and a lower probability of success in quitting during nicotine-patch treatment.,

CONCLUSIONS

Nicotine sustains tobacco addiction, a major cause of disability and premature death, by acting on nicotinic cholinergic receptors in the brain to trigger the release of dopamine and other neurotransmitters. Release of dopamine, glutamate, and GABA is particularly important in the development of nicotine dependence, and CRF may play a key role in withdrawal. Neuroadaptation and tolerance involve changes in nicotinic receptors and neural plasticity. Nicotine addiction occurs when smokers come to rely on smoking to modulate mood and arousal, relieve withdrawal symptoms, or both. Light or occasional smokers smoke mainly for positive reinforcement in specific situations. Genetic studies indicate that nicotinic receptor subtypes and the genes involved in neuroplasticity and learning play a part in the development of dependence. People with psychiatric or substance-abuse disorders, who account for a large proportion of current smokers, have an increased susceptibility to tobacco addiction. Nicotine is metabolized primarily by the enzyme CYP2A6, and variation in the rate of nicotine metabolism contributes to differences in vulnerability to tobacco dependence and the response to smoking-cessation treatment. An increased understanding of the mechanisms of nicotine addiction has led to the development of novel medications (e.g., varenicline) that act on specific nicotinic receptor subtypes. The development of other drugs that act on nicotinic receptors and other mediators of nicotine addiction is likely to further enhance the effectiveness of smoking-cessation pharmacotherapy.

Acknowledgments

Supported by grants from the Flight Attendants Medical Research Institute and the National Institute on Drug Abuse (U.S. Public Health Service grants DA02277 and DA20830).

I thank Marc Olmsted for editorial assistance on an earlier version of the manuscript.

Footnotes

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

References

9. Tapper AR, McKinney SL, Nashmi R, et al. Nicotine activation of alpha4[* receptors: sufficient for reward, tolerance, and sensitization. Science. 2004;306:1029-32. [ PubMed] Google Scholar]

31. Knott V, Heenan A, Shah D, Bolton K, Fisher D, Villeneuve C. Electrophysiological evidence of nicotine's distracter-filtering properties in non-smokers. J Psychopharmacol. 2009 November 25; (Epub ahead of print) [[ PubMed] Google Scholar]

47. Benowitz NL. Compensatory smoking of low yield cigarettes. In: Shopland DR, Burns DM, Benowitz NL, Amacher RH, editors. Risks associated with smoking cigarettes with low machine-measured yields of tar and nicotine. Bethesda, MD: National Institutes of Health; 2001. p. 3964. (NIH publication no. 02-5074.) [ Google Scholar]

64. Lynch BS, Bonnie RJ. Growing up tobacco free - preventing nicotine addiction in children and youths. Washington, DC: National Academy Press; 1994. The nature of nicotine addiction; pp. 28-68. [ Google Scholar]

65. Johnston LD, O'Malley PM, Bachman JG, Schulenberg JE. Monitoring the future: national survey results on drug use, 1975-2006. Bethesda, MD: National Institute on Drug Abuse; 2007. (NIH publication no. 07-6205.) [ Google Scholar]

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Neal L. Benowitz, M.D. Cigarette smoking remains a leading cause of preventable disease and premature death in the United States and other countries. On average, 435,000 people in the United States die prematurely from smoking-related diseases each year; overall, smoking causes 1 in 5 deaths.

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Biology of Nicotine Addiction by Dr. David Sachs

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Answers the questions that every smoker who has tried to quit and can't asks themselves. Why do I smoke? Why can't I just stop smoking? Provides insight into the biology of nicotine addiction and effective smoking cessation treatment.

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Smoking causes many kinds of cancer, including lung and throat

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#badlungs
#cancer
#smokingkills
#Smoking
#addiction
#whysmoke
#killspeople
#secondhandsmoke
#nicotine
#whysmoke

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Smoking has been found to have bad effects to health.