Nicotine Use Disorder

Tobacco use is the leading cause of preventable death in the world. Tobacco use is directly related to a higher risk of chronic obstructive pulmonary disease (COPD), cardiovascular diseases, and various cancers. Nicotine, the psychoactive component of tobacco, stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systems. Nicotine is highly addictive through its effects on the dopaminergic system. Treatment includes medications to prevent cravings, nicotine-replacement therapy, and psychotherapy.

Last update:

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp



Nicotine use disorder is defined as the chronic (> 12 months) maladaptive use of tobacco.

  • Most common substances: cigarettes, chewing tobacco
  • Intoxication: 
    • Much milder symptoms than are present in intoxication with other substances
    • Presents with mild restlessness/anxiety and increased GI motility 
  • Withdrawal: 
    • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
    • Mild physical symptoms: weight gain, poor concentration
    • Mild psychological symptoms: depression, perceived need to use the substance 
  • Tolerance: 
    • Need to increase the dose of the substance to achieve desired effect (diminished effect if using the same amount of the substance)


  • Tobacco use is the leading cause of preventable deaths worldwide. 
  • Prevalence: 
    • 15% of adults in the United States smoke regularly.
    • Higher in those with other comorbid psychiatric disorders such as bipolar disorder (70%), schizophrenia (90%), or other substance use disorders (70%) 
    • Smoking rates among young people in the United States are decreasing. 
  • Level of education is a protective factor in tobacco use.


Nicotine is the main psychoactive component of tobacco:

  • Agonist at the nicotinic subtype of acetylcholine receptor in the central nervous system
  • Activates the dopaminergic pathway from the ventral tegmental area to the cerebral cortex to produce its rewarding effects 
  • Leads to increasing circulation of the following neurotransmitters:
    • Norepinephrine
    • Epinephrine
    • Beta-endorphin
    • Adrenocorticotropic hormone
    • Cortisol

Only 25% of inhaled nicotine enters the bloodstream, but it reaches the brain in 15 seconds.

Clinical Presentation

Active nicotine use

  • Immediate effects of nicotine include improved attention and elevated mood.
  • Usually, there are no severe intoxication symptoms from tobacco use.
  • Nicotine intoxication: 
    • Nausea/vomiting 
    • Diarrhea
    • Tachycardia, elevated blood pressure 
    • Tremor
    • Cold sweats
  • Note: Nicotine is a CNS stimulant but a skeletal muscle relaxant.

Nicotine withdrawal

  • Intense craving
  • Dysphoria
  • Anxiety
  • Poor concentration
  • Increased appetite, weight gain
  • Irritability, restlessness, and insomnia

Management and Complications

Pharmacotherapy for nicotine use disorder

  • Nicotine-replacement therapy:
    • 1st-line treatment; doubles chances of cessation
    • Available as transdermal patch, gum, lozenge, nasal spray, and inhaler
  • Nicotine cessation: 
    • Varenicline: 
      • Partial agonist to the alpha-4 beta-2 (α4β2) nicotinic cholinergic receptor 
      • Mimics the action of nicotine
      • Reduces the rewarding effects of nicotine
      • Prevents withdrawal symptoms
      • Side effects: sleep disturbance, depressed mood
    • Bupropion: 
      • Inhibitor of dopamine and norepinephrine reuptake
      • Helps reduce cravings and withdrawal symptoms
      • Side effects: tachycardia, insomnia, headaches, seizures in bulimic patients (contraindicated in this group)

Psychotherapy and preventive measures for nicotine use disorder

  • Behavioral counseling:
    • Includes face-to-face or phone sessions, print materials, and software programs 
    • The goal is to help eliminate cues for smoking.
  • Motivational interviewing: 
    • Offered by providers to patients to uncover internal reasons for tobacco cessation 
    • The 1st step is to set a “quit date.”
  • Prevention and education are recommended in school-aged children and adolescents. 
  • Public health policies such as a ban on public smoking

Management of nicotine withdrawal

  • Symptomatic treatment 
  • Supportive, psychosocial interventions (e.g., contingency management, groups, etc.)


  • Smoking increases the risk for several types of cancers: 
    • Lung cancer: Tobacco smoking is the most common risk factor for the most deadly form of cancer in the United States.
    • Chronic obstructive pulmonary disease (COPD): 90% of cases of COPD can be attributed to tobacco smoking.
    • Esophageal cancer
    • Gastric cancer
    • Renal cell carcinoma
    • Transitional cell carcinoma
    • Salivary gland tumors
    • Cervical cancer
  • Cardiovascular diseases (atherosclerosis, angina)
  • Vasculitis (Buerger disease)
  • Pregnancy-related complications: 
    • Low birth weight
    • Preterm labor
    • Placental problems
    • Intrauterine growth restriction 
    • Sudden infant death syndrome
    • Ectopic pregnancy
  • Secondhand smoke 
    • Refers to involuntary exposure to tobacco smoke 
    • Similar complications as above although in lower numbers

Benefits of smoking cessation

Short-term benefits (< 12 months):

  • Lowered heart rate and blood pressure
  • Return of blood carbon monoxide level to normal
  • Improved circulation and lung function 
  • Decreased coughing and shortness of breath 
  • Women who stop smoking during the 1st trimester reduce their risk of low birth weight to that of women who never smoked.

Long-term benefits (> 12 months):

  • Increased life expectancy 
  • Decreased risk of lung cancer, myocardial infarction, cerebrovascular diseases  
  • Decreased risk of oropharyngeal, bladder, cervical, lung, and pancreatic cancer

Differential Diagnosis

  • Organophosphate poisoning: chemicals commonly found in insecticides, classified as irreversible cholinesterase inhibitors. When these chemicals are ingested in toxic amounts, symptoms include salivation, lacrimation, urination, diarrhea, GI upset, and emesis. These symptoms are similar to nicotine intoxication. However, the severity of symptoms observed in organophosphate poisoning is unlikely to occur from excessive tobacco consumption. 
  • Cannabis use disorder: cannabis is the most commonly used illicit substance worldwide. Intoxication symptoms include euphoria, laughter, lethargy, impaired reaction time, conjunctival injection, and increased appetite. Withdrawal symptoms include irritability, anxiety, insomnia, and decreased appetite. While the withdrawal symptoms of irritability and anxiety are similar in cannabis and tobacco use, appetite is usually increased during withdrawal from tobacco use. Careful history taking of the substance ingested will also help distinguish the diagnosis.


  1. Ganti L, et al. (2016). First Aid for the Psychiatry Clerkship. 4th ed., Chapter 7, Substance-related and addictive disorders, pages 80, 94.
  2. Bhushan V, et al. (2019). First Aid for the USMLE Step 1. 29th ed. McGraw-Hill Education/Medical. Page 564.
  3. Rigotti N. (2021). Overview of smoking cessation management in adults. UpToDate. Retrieved April 30, 2021, from 
  4. Sadock BJ, Sadock VA, & Ruiz P. (2014). Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.), Chapter 20, Substance use and addictive disorders, pages 680–685. Philadelphia, PA: Lippincott Williams and Wilkins.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.