Nicotine dependence

Definition

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. Nicotine dependence has also been conceptualized as a chronic, relapsing disease. 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."

Nicotine dependence leads to heavy smoking and causes severe withdrawal symptoms and relapse back to smoking. Relapse should not frustrate the nicotine user from trying to quit again. 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." Symptoms of nicotine dependence include irritability, anger, impatience, and problems in concentrating.

Diagnosis

There are different ways of measuring nicotine dependence. 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.

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chronic drug administration, which is revealed by the occurrence of signs of physiological dysfunction when the drug is withdrawn; further, this dysfunction can be reversed by the administration of drug". The long use of Fagerström Test for Nicotine Dependence is supported by the existence of significant preexisting research, and its conciseness.

The 4th edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) had a nicotine dependence diagnosis which was defined as "...a cluster of cognitive, behavioral, and physiological symptoms..."

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

Mechanisms

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

Biomolecular

Pre-existing cognitive and mood disorders may influence the development and maintenance of nicotine dependence. Nicotine is a parasympathomimetic stimulant that binds to and activates nicotinic acetylcholine receptors in the brain, and several neuropeptides. 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. Nicotine also stimulates nicotinic acetylcholine receptors in the adrenal medulla, resulting in increased levels of adrenaline and beta-endorphin. 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. These complex effects of nicotine on the brain are still not well understood.

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

Neuroplasticity within the brain's reward system occurs as a result of long-term nicotine use, leading to nicotine dependence. There are genetic risk factors for developing dependence. 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. The single-nucleotide polymorphisms (SNPs) rs6474413 and rs10958726 in CHRNB3 are highly correlated with nicotine dependence. There is a relationship between CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptors and complete smoking cessation.

Psychosocial

In addition to the specific neurological changes in nicotinic receptors, there are other changes that occur as dependence develops. 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.

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). Evidence-based medicine can double or triple a smoker's chances of quitting successfully.

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.

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.

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. 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. The combination of pharmacotherapy and psychosocial interventions has been shown to be especially effective.

Emerging Medical Treatment

A non-invasive, brain-based therapy called rTMS (repetitive transcranial magnetic stimulation) gained FDA approval in 2020 for treating nicotine addiction and aiding the quitting process. Studies have found patients who undergo rTMS have reduced cigarette cravings and number of cigarettes smoked, as well as greater long term success with cessation. While this therapy is relevantly new for treating nicotine additions, it has a longer history as a therapeutic treatment for Major depressive disorder, Obsessive-compulsive disorder, and migraines. Side effects of this therapy are relatively mild because of the noninvasive nature of the treatment.

Epidemiology

First-time nicotine users develop a dependence about 32% of the time. There are approximately 976 million smokers in the world. 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. 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. 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. There is an increased frequency of nicotine dependence in people with anxiety disorders. 6% of smokers who want to quit smoking each year are successful at quitting. Nicotine withdrawal is the main factor hindering smoking cessation. 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." E-cigarettes may result in starting nicotine dependence again. 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.

Concerns

Nicotine dependence results in substantial mortality, morbidity, and socio-economic impacts. There is strong evidence that vaping induces symptoms of dependence in users. 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.

Notes

Bibliography

References

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