Nicotine dependence

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Nicotine dependence
Other namestobacco dependence; tobacco use disorder, cigarette dependence
Video of medical explanation of nicotine dependence and its health effects
Complications Health effects of tobacco
Prognosis 10-year shorter lifespan [notes 1]
Prevalence1.2 billion tobacco users globally (2022) [2]
Deaths8 million per year (2023) [3]

Nicotine dependence [notes 2] is a state of substance dependence on nicotine. [4] It is a chronic, relapsing disease characterized by a compulsive craving to use the drug despite social consequences, loss of control over drug intake, and the emergence of withdrawal symptoms. [8] Tolerance is another component of drug dependence. [9] Nicotine dependence develops over time as an individual continues to use nicotine. [9] While cigarettes are the most commonly used tobacco product, all forms of tobacco use—including smokeless tobacco and e-cigarette use—can cause dependence. [3] [10] Nicotine dependence is a serious public health problem because it leads to continued tobacco use and the associated negative health effects. Tobacco use is one of the leading preventable causes of death worldwide, causing more than 8 million deaths per year and killing half of its users who do not quit. [3] [11] Current smokers are estimated to die an average of 10 years earlier than non-smokers. [1]

Contents

According to the World Health Organization, "Greater nicotine dependence has been shown to be associated with lower motivation to quit, difficulty in trying to quit, and failure to quit, as well as with smoking the first cigarette earlier in the day and smoking more cigarettes per day." [12] The WHO estimates that there were 1.24 billion tobacco users globally in 2022, with the number projected to decline to 1.20 billion in 2025. [2] Of the 34 million smokers in the United States in 2018, 74.6% smoked every day, indicating the potential for some level of nicotine dependence. [13] There is an increased incidence of nicotine dependence in individuals with psychiatric disorders, such as anxiety disorders and substance use disorders. [14] [15]

Various methods exist for measuring nicotine dependence. [6] Common assessment scales for cigarette smokers include the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual of Mental Disorders criteria, the Cigarette Dependence Scale, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. [6]

Nicotine is a parasympathomimetic stimulant [16] that binds to nicotinic acetylcholine receptors in the brain. [17] Neuroplasticity within the brain's reward system, including an increase in the number of nicotine receptors, occurs as a result of long-term nicotine use and leads to nicotine dependence. [4] In contrast, the effect of nicotine on human brain structure (e.g., gray matter and white matter) is less clear. [18] Genetic risk factors contribute to the development of dependence. [19] For instance, genetic markers for specific types of nicotinic receptors (the α5–α3–β4 nicotinic receptors) have been linked to an increased risk of dependence. [19] Evidence-based treatments—including medications such as nicotine replacement therapy, bupropion, varenicline, or cytisine, and behavioral counseling—can double or triple a smoker’s chances of successfully quitting. [20]

Definition

A National Institute on Drug Abuse video entitled Anyone Can Become Addicted to Drugs. [21]

Nicotine dependence is defined as a neurobiological adaptation to repeated drug exposure that is manifested by highly controlled or compulsive use, the development of tolerance, experiencing withdrawal symptoms upon cessation including cravings, and an inability to quit despite harmful effects. [9] Nicotine dependence has also been conceptualized as a chronic, relapsing disease. [20] A 1988 Surgeon General report states, "Tolerance" is another aspect of drug addiction [dependence] whereby a given dose of a drug produces less effect or increasing doses are required to achieve a specified intensity of response. Physical dependence on the drug can also occur, and is characterized by a withdrawal syndrome that usually accompanies drug abstinence. After cessation of drug use, there is a strong tendency to relapse." [9]

Nicotine dependence leads to heavy smoking and causes severe withdrawal symptoms and relapse back to smoking. [9] Nicotine dependence develops over time as a person continues to use nicotine. [9] Teenagers do not have to be daily or long-term smokers to show withdrawal symptoms. [22] Relapse should not frustrate the nicotine user from trying to quit again. [20] A 2015 review found "Avoiding withdrawal symptoms is one of the causes of continued smoking or relapses during attempts at cessation, and the severity and duration of nicotine withdrawal symptoms predict relapse." [23] Symptoms of nicotine dependence include irritability, anger, impatience, and problems in concentrating. [24]

Diagnosis

There are different ways of measuring nicotine dependence. [6] The five common dependence assessment scales are the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual of Mental Disorders , the Cigarette Dependence Scale, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. [6]

The Fagerström Test for Nicotine Dependence focuses on measuring physical dependence which is defined "as a state produced by chronic drug administration, which is revealed by the occurrence of signs of physiological dysfunction when the drug is withdrawn; further, this dysfunction can be reversed by the administration of drug". [6] The long use of Fagerström Test for Nicotine Dependence is supported by the existence of significant preexisting research, and its conciseness. [6]

The 4th edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) had a nicotine dependence diagnosis which was defines as "...a cluster of cognitive, behavioral, and physiological symptoms..." [6] In the updated DSM-5 there is no nicotine dependence diagnosis, but rather Tobacco Use Disorder, which is defined as, "A problematic pattern of tobacco use leading to clinically significant impairment or distress, as manifested by at least 2 of the following [11 symptoms], occurring within a 12-month period." [25]

The Cigarette Dependence Scale was developed "to index dependence outcomes and not dependence mechanisms". [6] The Nicotine Dependence Syndrome Scale, "a 19-item self-report measure, was developed as a multidimensional scale to assess nicotine dependence". [6] The Wisconsin Inventory of Smoking Dependence Motives "is a 68-item measure developed to assess dependence as a motivational state". [6]

Mechanisms

Traditional cigarettes are the most common delivery device for nicotine. [26] However, electronic cigarettes are becoming more popular. [27] Nicotine can also be delivered via other tobacco products such as chewing tobacco, snus, pipe tobacco, hookah, all of which can produce nicotine dependence. [28]

Biomolecular

Dopamine Dopamine.svg
Dopamine

Pre-existing cognitive and mood disorders may influence the development and maintenance of nicotine dependence. [29] Nicotine is a parasympathomimetic stimulant [16] that binds to and activates nicotinic acetylcholine receptors in the brain, [17] which subsequently causes the release of dopamine and other neurotransmitters, such as norepinephrine, acetylcholine, serotonin, gamma-aminobutyric acid, glutamate, endorphins, [30] and several neuropeptides. [31] Repeated 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. [30] This upregulation or increase in the number of nicotinic receptors significantly alters the functioning of the brain reward system. [32] With constant use of nicotine, tolerance occurs at least partially as a result of the development of new nicotinic acetylcholine receptors in the brain. [30] After several months of nicotine abstinence, the number of receptors go back to normal. [17] Nicotine also stimulates nicotinic acetylcholine receptors in the adrenal medulla, resulting in increased levels of adrenaline and beta-endorphin. [30] Its physiological effects stem from the stimulation of nicotinic acetylcholine receptors, which are located throughout the central and peripheral nervous systems. [33] 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. [34] These complex effects of nicotine on the brain are still not well understood. [34]

When these receptors are not occupied by nicotine, they are believed to produce withdrawal symptoms. [35] These symptoms can include cravings for nicotine, anger, irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger, weight gain, and difficulty concentrating. [36]

Neuroplasticity within the brain's reward system occurs as a result of long-term nicotine use, leading to nicotine dependence. [4] There are genetic risk factors for developing dependence. [19] For instance, genetic markers for a specific type of nicotinic receptor (the α5-α3-β4 nicotine receptors) have been linked to increased risk for dependence. [19] [37] 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. [38] The single-nucleotide polymorphisms (SNPs) rs6474413 and rs10958726 in CHRNB3 are highly correlated with nicotine dependence. [39] Many other known variants within the CHRNB3–CHRNA6 nicotinic acetylcholine receptors are also correlated with nicotine dependence in certain ethnic groups. [39] There is a relationship between CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptors and complete smoking cessation. [40] Increasing evidence indicates that the genetic variant CHRNA5 predicts the response to smoking cessation medicine. [40]

Psychosocial

In addition to the specific neurological changes in nicotinic receptors, there are other changes that occur as dependence develops.[ citation needed ] Through various conditioning mechanisms (operant and cue/classical), smoking comes to be associated with different mood and cognitive states as well as external contexts and cues. [32]

Treatment

There are treatments for nicotine dependence, although the majority of the evidence focuses on treatments for cigarette smokers rather than people who use other forms of tobacco (e.g., chew, snus, pipes, hookah, e-cigarettes).[ citation needed ] Evidence-based medicine can double or triple a smoker's chances of quitting successfully. [20]

Medication

There are eight major evidence-based medications for treating nicotine dependence: bupropion, cytisine (not approved for use in some countries, including the US), nicotine gum, nicotine inhaler, nicotine lozenge/mini-lozenge, nicotine nasal spray, nicotine patch, and varenicline. [41] These medications have been shown to significantly improve long-term (i.e., 6-months post-quit day) abstinence rates, especially when used in combination with psychosocial treatment. [20] The nicotine replacement treatments (i.e., patch, lozenge, gum) are dosed based on how dependent a smoker is—people who smoke more cigarettes or who smoke earlier in the morning use higher doses of nicotine replacement treatments.[ citation needed ] There is no consensus for remedies for tobacco use disorder among pregnant smokers who also use alcohol and stimulants. [7]

Vaccine

TA-NIC is a proprietary vaccine in development similar to TA-CD but being used to create human anti-nicotine antibodies in a person to destroy nicotine in the human body so that it is no longer effective. [42]

Psychosocial

Psychosocial interventions delivered in-person (individually or in a group) or over the phone (including mobile phone interventions) have been shown to effectively treat nicotine dependence. [41] These interventions focus on providing support for quitting and helping with smokers with problem-solving and developing healthy responses for coping with cravings, negative moods, and other situations that typically lead to relapse.[ citation needed ] The combination of pharmacotherapy and psychosocial interventions has been shown to be especially effective. [20]

Epidemiology

First-time nicotine users develop a dependence about 32% of the time. [43] There are approximately 976 million smokers in the world. [44] Estimates are that half of smokers (and one-third of former smokers) are dependent based on DSM criteria, regardless of age, gender or country of origin, but this could be higher if different definitions of dependence were used. [45] Recent data suggest that, in the United States, the rates of daily smoking and the number of cigarettes smoked per day are declining, suggesting a reduction in population-wide dependence among current smokers. [46] However, there are different groups of people who are more likely to smoke than the average population, such as those with low education or low socio-economic status and those with mental illness. [46] There is also evidence that among smokers, some subgroups may be more dependent than other groups.[ citation needed ] Men smoke at higher rates than do women and score higher on dependence indices; however, women may be less likely to be successful in quitting, suggesting that women may be more dependent by that criterion. [46] [47] There is an increased frequency of nicotine dependence in people with anxiety disorders. [14] 6% of smokers who want to quit smoking each year are successful at quitting. [48] Nicotine withdrawal is the main factor hindering smoking cessation. [49] A 2010 World Health Organization report states, "Greater nicotine dependence has been shown to be associated with lower motivation to quit, difficulty in trying to quit, and failure to quit, as well as with smoking the first cigarette earlier in the day and smoking more cigarettes per day." [50] E-cigarettes may result in starting nicotine dependence again. [51] Greater nicotine dependence may result from dual use of traditional cigarettes and e-cigarettes. [51] Like tobacco companies did in the last century, there is a possibility that e-cigarettes could result in a new form of dependency on nicotine across the world. [52]

Concerns

Nicotine use and addiction.

Nicotine dependence results in substantial mortality, morbidity, and socio-economic impacts. [48] Nicotine dependence is a serious public health concern due to it being one of the leading causes of avoidable deaths worldwide. [48] The medical community is concerned that e-cigarettes may escalate global nicotine dependence, particularly among adolescents who are attracted to many of the flavored e-cigarettes. [53] There is strong evidence that vaping induces symptoms of dependence in users. [54] Many organizations such the World Health Organization, American Lung Association, and Australian Medical Association do not approve of vaping for quitting smoking in youth, making reference to concerns about their safety and the potential that experimenting with vaping may result in nicotine dependence and later tobacco use. [55]

See also

Notes

  1. ↑ Current smokers are estimated to die an average of 10 years earlier than non-smokers. [1]
  2. ↑ Nicotine dependence [4] is also variously known as cigarette dependence, [5] tobacco dependence, [6] or tobacco use disorder. [7]

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">Tobacco smoking</span> Practice of burning tobacco and breathing the resulting smoke

Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed to have begun as early as 5000–3000 BC in Mesoamerica and South America. Tobacco was introduced to Eurasia in the late 17th century by European colonists, where it followed common trade routes. The practice encountered criticism from its first import into the Western world onwards but embedded itself in certain strata of a number of societies before becoming widespread upon the introduction of automated cigarette-rolling apparatus.

<span class="mw-page-title-main">Smoking cessation</span> Process of discontinuing tobacco smoking

Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often makes the process of quitting difficult.

<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">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">Nicotine patch</span> Transdermal patch that releases nicotine into the body

A nicotine patch is a transdermal patch that releases nicotine into the body through the skin. It is used in nicotine replacement therapy (NRT), a process for smoking cessation. Endorsed and approved by the U.S. Food and Drug Administration (FDA), it is considered one of the safer NRTs available for the treatment of tobacco use disorder.

Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain medications such as benzodiazepines, opioids, stimulants, antiepileptics and antidepressants, as well as the recreational misuse of drugs such as alcohol, opioids and benzodiazepines. The higher the dose used, the greater the duration of use, and the earlier age use began are predictive of worsened physical dependence and thus more severe withdrawal syndromes. Acute withdrawal syndromes can last days, weeks or months. Protracted withdrawal syndrome, also known as post-acute-withdrawal syndrome or "PAWS", is a low-grade continuation of some of the symptoms of acute withdrawal, typically in a remitting-relapsing pattern, often resulting in relapse and prolonged disability of a degree to preclude the possibility of lawful employment. Protracted withdrawal syndrome can last for months, years, or depending on individual factors, indefinitely. Protracted withdrawal syndrome is noted to be most often caused by benzodiazepines. To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes.

Nicotine gum is a chewing gum containing the active ingredient nicotine polacrilex. It is a type of nicotine replacement therapy (NRT) used alone or in combination with other pharmacotherapy for smoking cessation and for quitting smokeless tobacco.

<span class="mw-page-title-main">Health effects of tobacco</span> Circumstances, mechanisms, and factors of tobacco consumption on human health

Tobacco products, especially when smoked or used orally, have serious negative effects on human health. Smoking and smokeless tobacco use are the single greatest causes of preventable death globally. Half of tobacco users die from complications related to such use. Current smokers are estimated to die an average of 10 years earlier than non-smokers. The World Health Organization estimates that, in total, about 8 million people die from tobacco-related causes, including 1.3 million non-smokers due to secondhand smoke. It is further estimated to have caused 100 million deaths in the 20th century.

<span class="mw-page-title-main">Cytisine</span> Chemical compound

Cytisine, also known as baptitoxine, cytisinicline, or sophorine, is an alkaloid that occurs naturally in several plant genera, such as Laburnum and Cytisus of the family Fabaceae. It has been used medically to help with smoking cessation. It has been found effective in several randomized clinical trials, including in the United States and New Zealand, and is being investigated in additional trials in the United States and a non-inferiority trial in Australia in which it is being compared head-to-head with the smoking cessation aid varenicline. It has also been used entheogenically via mescalbeans by some Native American groups, historically in the Rio Grande Valley predating even peyote.

<span class="mw-page-title-main">Varenicline</span> Nicotinic receptor agonist

Varenicline, sold under the brand names Chantix and Champix among others, is a medication used for smoking cessation and for the treatment of dry eye syndrome. It is a nicotinic acetylcholine receptor partial agonist. When activated, this receptor releases dopamine in the nucleus accumbens, the brain's reward center, thereby reducing cravings and withdrawal symptoms with smoking cessation, although less pronounced than a full agonist.

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">Nicotine withdrawal</span> Process of withdrawing from nicotine addiction

Nicotine withdrawal is a group of symptoms that occur in the first few weeks after stopping or decreasing use of nicotine. Symptoms include intense cravings for nicotine, anger or irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger, weight gain, and difficulty concentrating. Withdrawal symptoms make it harder to quit nicotine products, and most methods for quitting smoking involve reducing nicotine withdrawal. Quit smoking programs can make it easier to quit. Nicotine withdrawal is recognized in both the American Psychiatric Association Diagnostic and Statistical Manual (DSM) and the WHO International Classification of Diseases (ICD).

<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.

Schizophrenia and tobacco smoking have been historically associated. Smoking is known to harm the health of people with schizophrenia.

<span class="mw-page-title-main">Cannabis use disorder</span> Continued use of cannabis despite clinically significant impairment

Cannabis use disorder (CUD), also known as cannabis addiction or marijuana addiction, is a psychiatric disorder defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and ICD-10 as the continued use of cannabis despite clinically significant impairment.

<span class="mw-page-title-main">Smoking in Syria</span>

Smoking in Syria is steadily increasing in popularity amongst the Syrian population, mainly in the forms of cigarettes or narghiles. In Syria, the General Organization of Tobacco manages the growth and exportation of tobacco products. Syrians collectively spend about $600 million per year on tobacco consumption. As of 2010, 20% of women and 60% of men smoke and 98% of the overall population is affected by passive smoking. Narghiles and cigarettes are the two main forms of tobacco consumption. Despite the assumption that smoking, specifically the narghile, is embedded in Syrian culture, this phenomenon has only recently become widespread. Health officials are currently working on smoking cessation programs and policies, to remove this idea that smoking in Syria is an essential part of the culture, to educate regarding health effects, and to prevent citizens from smoking in public places.

Jed Eugene Rose is an American academic professor, inventor and researcher in the field of nicotine and smoking cessation. Rose is presently the President and CEO of the Rose Research Center, LLC in Raleigh, North Carolina. Additionally, he is the Director of the Duke Center for Smoking Cessation at Duke University Medical Center.

Exposure to nicotine, from conventional or electronic cigarettes during adolescence can impair the developing human brain. E-cigarette use is recognized as a substantial threat to adolescent behavioral health. 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. 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 can also prime the adolescent brain for addiction to other drugs such as cocaine. Exposure to nicotine and its great risk of developing an addiction, are areas of significant concern.

Nicotine vaccine is a novel immunological strategy for treating nicotine addiction. Nicotine vaccine uses active immunization as the methodology to create polyclonal antibodies to the antigens, which is then used to treat drug abuse. The immune system is then able to identify nicotine as a foreign substance and initiate an immune reaction targeting the drug. As a result, the quantity of nicotine that enters the brain would decrease after receiving the vaccine. In preclinical studies, nicotine vaccines have demonstrated the ability to combat the negative effects of nicotine abuse, but none of the developed vaccines has been authorized for use in clinical trials as a smoking cessation strategy. Theoretically, the decrease of nicotine's rewarding effects should result in smoking cessation. Some companies have tested candidate vaccines in clinical trials, but evidence failed to show the adequate antibody responses or exhibit superior efficacy to factors concerning placebo.

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