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Nicotine Withdrawal

Tobacco Withdrawal

Nicotine withdrawal refers to somatic withdrawal symptoms characterized by irritability, anxiety, depression, and restlessness, arising from nicotine cessation. It usually begins within 24 hours of sudden cessation, or reduction in the amount of nicotine use.


Nicotine withdrawal is defined by DSM-IV-TR as a condition in which a person exhibits at least four of the following symptoms after cessation of nicotine use. The symptoms include:

Symptoms typically appear two hours after the last cigarette and a peak is noted between 24 and 48 hours after cessation. There can be a variation in the course of symptoms and the time course of withdrawal [9]. Craving for nicotine is also considered as a very important element in withdrawal syndrome. The two most common symptoms are nicotine craving and loss of concentration. It can also affect psychomotor and cognitive abilities of the person.

  • Treatments were collapsed into placebo, monotherapy, and combination therapy conditions because sample sizes were too small (e.g., n 11 with GAD in the placebo group) to permit comparisons of individual treatments.[ncbi.nlm.nih.gov]
  • METHODS: Adult Italian smokers, 366 in all, were assessed via the MNWS-R together with rating scales measuring cigarette dependence, alcohol use, anxiety sensitivity and negative affect at baseline and after 3 months.[ncbi.nlm.nih.gov]
  • Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Ardeystraße 67, 44139, Dortmund, Germany. nitsche@ifado.de. 6 Department of Neurology, University Medical Hospital Bergmannsheil, Bürkle de la Camp-Platz[ncbi.nlm.nih.gov]
Heavy Tobacco Use
  • Each patient had a history of heavy tobacco use and experienced dramatic and sustained clinical improvement within hours of transdermal nicotine replacement.[ncbi.nlm.nih.gov]
Panic Attacks
  • Individuals who did not experience a panic attack posthyperventilation who were also low in anxiety sensitivity reported the lowest levels of nicotine withdrawal.[ncbi.nlm.nih.gov]
  • But for people with panic disorder (PD), going without a cigarette may trigger a panic attack. According to a recent study conducted by Teresa M.[goodtherapy.org]
  • Other withdrawal symptoms may include constipation, cough, dizziness, drowsiness, headache, impulsivity, fatigue, flu symptoms, mood swings, mouth ulcers, and increased dreaming.[en.wikipedia.org]
  • Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study.[ncbi.nlm.nih.gov]
Compulsive Disorder
  • Other anxiety disorders (specific phobias, obsessive-compulsive disorder, and post-traumatic stress disorder) were not assessed, making it impossible to rule out additional comorbidity with these anxiety disorders.[ncbi.nlm.nih.gov]
  • Agitation, with the Sedation-Agitation Scale (SAS), and delirium, with the Intensive Care Delirium Screening Checklist (ICDSC), were tested twice daily during the ICU stay. Agitation and delirium were defined by SAS 4 and ICDSC 4, respectively.[ncbi.nlm.nih.gov]
  • […] restraint related to agitation events.[ccforum.biomedcentral.com]
  • Shamila describes how nicotine withdrawal is an under-recognised and easily reversible contributor to agitation in the final days of life.[eapcnet.wordpress.com]
  • Quitting smoking can leave you with feelings of depression and anxiety, insomnia, agitation and irritability and restlessness. Some of these symptoms will take longer to subside than others.[addiction.lovetoknow.com]
  • Disorder (ADHD): any subtype: inattentive, hyperactive or combined.[ncbi.nlm.nih.gov]
  • Sullivan Lab Evidence Project psychiatric genetics database ( 46 ) for genome-wide linkage and association findings in the 2 LOD support interval flanking our MLS annotates findings with bipolar, schizophrenia, major depressive disorder, Attention Deficit Hyperactivity[dx.doi.org]
  • […] and then found a possible association between smoking and hyperactive delirium.[ccforum.biomedcentral.com]
Cognitive Deficit
  • These findings suggest that repeated nicotine replacement therapy over a period of 8 hours can improve cognitive deficits associated with nicotine withdrawal.[ncbi.nlm.nih.gov]
  • A heavy smoking, lactating mother delivered a baby that exhibited spontaneous tremors, fluctuations of muscular rigidity, and opisthotonus at 48 hours of life.[ncbi.nlm.nih.gov]


As mentioned in presentation section, diagnostic criteria for nicotine withdrawal is based on DSM-IV. Patients with withdrawal symptoms will have any of the four symptoms including insomnia, irritability, anxiety, difficulty in concentration, restlessness, depression or decreased heart rate. Craving for nicotine is also noted. Practice guidelines suggest that each patient should be systematically assessed for nicotine use. It should be a part of vital signs assessment. Documentation of smoking status helps in identifying nicotine dependency and nicotine abstinence. Degree of nicotine dependency can be assessed, once dependency is diagnosed. The Fagerström Test for Nicotine Dependence is usually used to see whether nicotine replacement may be needed. A number of other scales are developed to assess nicotine withdrawal. This includes Shiffman-Jarwik scale, which assess craving, psychological symptoms, and changes in appetite. Wisconsin Smoking withdrawal scale is based on factor analysis designed for DSM-IV criteria.


Use of nicotine is one of the most preventable causes of death in the world. Educating patients about the importance of nicotine cessation is a very important step in treatment. This is particularly true considering the fact that 90% of the patients find it difficult to quit smoking or nicotine use. Brief interventions and pharmacologic interventions are other strategies used in cessation of nicotine. The long-term abstinence rate of smokers who use medication or counselling is 25-30%. The success of nicotine abstinence effort increases to 40% when both the interventions are used. Treatment plan for a patient should assess the motivation of the patient to stop nicotine use.

Brief psychological interventions are used to help about 70% of not-so-motivated smokers to quit [10]. This intervention is based on the principle of motivational interviewing (MI). Here the clinician’s questions are designed in such a way as to elicit the client’s motivation to change. Brief interventions from the primary care setting also helps the patient to quit smoking. These interventions are based on five A’s – asking, advising, assessing, assisting, and arranging. Patients may also be referred to intensive counselling programs. These programs use repeated face-to-face educational programs that are customized for the patient. This may be done individually or in a group and usually has a psychotherapy component added to it for effect. They are known to have better prognosis. They use social supports, relaxation training, and cognitive structuring.

Pharmacologic interventions are found to be equally effective in nicotine cessation. In nicotine replacement therapy, nicotine is delivered to aid in withdrawal, while allowing the patient to break the habit. This is important as withdrawal symptoms often dampen the ability to go forward with nicotine abstinence. Nicotine gums can be kept between the cheek and the gum for easy absorption. This helps in relieving withdrawal symptoms. Nicotine patches may also be used to provide nicotine for a longer duration. This can be transdermally delivered over a period of 16-24 hours. These patches can be used daily for few weeks and then tapered gradually over 6-12 weeks. Other options include nicotine nasal sprays, inhalers, and lozenges.

Non-nicotine medications like bupropion hydrochloride are also effective in nicotine cessation. Bupropion therapy is usually given for a period of 12 weeks. Varenicline is also an approved medication for nicotine dependence. Herbal supplements and laser treatment are tried as alternative treatment options for withdrawal symptoms. Hypnosis and acupuncture are also available as options. These methods should be used as supplements to pharmacologic treatments for successful treatment of condition.


Abstinence rate are affected by different factors in different groups. Abstinence rate is lower in patients with high levels of nicotine dependence and those with a history of depression. Successful nicotine abstinence can be encouraged by nicotine replacement or bupropion. Intensive counselling help to improve abstinence rates. Oral nicotine habit when replaced by other oral habits like food may result in weight gain. Replacing nicotine with water, and increasing exercise help in successful cessation of nicotine.


As name indicates, deprivation of nicotine is the cause for nicotine withdrawal symptoms. The physiological responses of the body when the substance is removed result in different symptoms. There are several etiological theories for this condition. According to the ‘opponent process’ theory an opposing homeostatic reaction to drug intake is responsible for withdrawal symptoms [3]. The overall effect of drug intake is actually the sum total of drug effect and the opposing homeostatic process. When the drug is removed only the opposing reaction exists, which has an opposite effect to that of the drug. Many non-pharmacologic factors of nicotine intake such as conditioning and expectancy may also affect the behavior during withdrawal.


Epidemiological studies show that about 1.1 billion people in the whole world are smokers, and it is more prevalent in the developing countries. In United States, about 69.6 million people above the age group of 12 years use tobacco products. The use of tobacco has decreased since the last decade. Studies show that about 37% of smokers have had some symptoms related to cessation of smoking [4]. About 76% of smokers had at least one withdrawal symptom in their lifetime. Prevalence of individual symptoms among smokers who tried to quit ranged from 22% to 62% [5]. Reports on incidence of withdrawal symptoms syndrome is negligible. In one of the study, the incidence of symptoms range from 18% to 55%, two days post cessation of smoking. Most of the studies show that more than half of the smokers who try to quit have significant withdrawal symptoms.

Sex distribution
Age distribution


Chronic exposure to nicotine results in an increased pool of nicotinic acetyl cholinergic receptors which direct the symptoms of withdrawal syndrome. It might also affect the effort to maintain abstinence from nicotine. Receptor availability at the somatosensory cortex and the urge to relieve the symptoms of withdrawal are negatively correlated. According to biological conceptualizations of drug dependency and withdrawal, receptor changes are responsible for the development of withdrawal symptoms. Nicotinic acetyl cholinergic receptors are the mediators of manifestations of withdrawal according to this theory [6]. Central and peripheral nicotinic acetyl cholinergic receptors mediate the somatic and motivational aspects of withdrawal. A recent theory suggests that abstinence results in decrease of dopamine release [7]. Abstinence of nicotine results in decreased dopaminergic activity and sensitivity of nicotine receptors of brain. Decrease of dopamine activity in mesolimbic system is implicated in the clinical manifestations of withdrawal symptoms, while decrease in dopamine in nucleus accumbens is considered to mediate the motivational components of withdrawal [8]. This has a negative effect and diminishes reward sensitivity in patients. Increased negative effect leads to manifestations like anger, anxiety and depression. Smoking is also known to increase the metabolism of several medications like cyclobenzaprine, naproxen, verapamil, and propanalol. Levels of these medications may increase in the blood when nicotine is abstained.


Nicotine is highly addictive and most of the patients find it hard to quit nicotine. The best approach possible to control exposure to nicotine is to educate the public about the dangers of nicotine. This will help in preventing the setting in of addiction. Negative health effects and cost of exposure should be clearly explained to patients. Quitting smoking is the only possible way to deter withdrawal symptoms.


Nicotine withdrawal refers to somatic withdrawal symptoms characterized by irritability, anxiety, depression, and restlessness, arising from nicotine cessation. The condition usually begins within 24 hours of sudden cessation, or reduction in the amount of nicotine use. Patients will also have a craving for nicotine. Withdrawal can considerably affect psychomotor and cognitive functioning. Symptoms are considered to be caused by nicotine deprivation in the body. Withdrawal symptoms may subside over 2 to 3 weeks. As abstinence level increases, structure and intensity of symptoms remain constant over this time period. Studies show that severity of nicotine withdrawal is related to relapse [1] [2]. Addiction to nicotine is one of the leading causes of death in the world.

Patient Information

Nicotine withdrawal refers to the distressing physical symptoms that appear during nicotine cessation. It usually begins within half an hour of last use of the addictive substance. Intensity of symptoms often depend on the level of dependency. Severity of symptoms is based on the duration of exposure to the substance and the amount of nicotine used in a day. The most common symptoms of nicotine withdrawal include depressed mood, insomnia, anxiety, irritability, nausea, difficulty in concentrating, and craving for nicotine. The symptoms usually peak within 2-3 days of last use. In most of the people the symptoms go within two to three weeks, but in some it may persist for months.

There are many ways to quit nicotine. Smoking cessation programs offered in primary health centers, hospitals, health departments and work sites, provide brief interventions to continue the motivation to quit smoking. Nicotine replacement therapy is yet another effective treatment method to relieve the symptoms. In this method, nicotine is delivered to the body while helping the patient to break the habit of nicotine use. It provides low doses of nicotine. Nicotine gums, nasal sprays, lozenges and skin patches are all methods of providing nicotine in low doses, over a longer duration. This helps to relieve cravings and to control the withdrawal symptoms. Many non-nicotine prescription medications are also used in nicotine cessation. Most of these medications work by inhibiting the pleasant effects of nicotine. This breaks the dependency on the substance and aids in quitting.
Nicotine cessation is often associated with weight gain in many patients. Those who have had depression may have a relapse with nicotine abstinence. Educating the public regarding the harmful effects of nicotine is the best way to prevent nicotine-related complications.



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  2. Shiffmann S, Enberg JB, Patty JA, et al. A day at a time: predicting smoking lapse from daily urge. J Abnorm Psychol. 1997;106:104-116. 
  3. Koob GF, LeMoal M. drug addiction, dysregulation of reward and allostasis. Neuropsychopharmacol. 2001;24:97-129.
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  5. Breslau N, Kilbey MM, Andreski P. Nicotine withdrawal symptoms and psychiatric disorders: finding from an epidemiological study of young adults. Am J Psy. 1992;149:464-469. 
  6. Danny J, Heinemann S. Molecular and cellular aspects of nicotine abuse. Neuron. 1996;16:905-908. 
  7. Kenny PJ, Markou A. Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav. 2001;70:531-549.
  8. Watkins S, Koob GF, Markou A. Neural mechanisms underlying nicotine addiction: Acute positive reinforcement and withdrawal. Nicotine and Tobacco Res.2000;2:19-37.
  9. Piasceki T, Fiore M, Baker T. Profiles in discouragement: two studies in variability in the time course of smoking withdrawal symptoms. J Abnormal Psychol. 1997;107:238-251. 
  10. Rollnick S, Butler CC, Stott N. Helping smokers make decisions: the enhancement of brief intervention for general medicine practice. Patient Educ Counsel. 1997;31:191-203. 

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Last updated: 2019-06-28 11:23