Nicotine Dependence

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Nicotine Dependence

• Laurie Zawertailo, PhD
• Adjunct Research Scientist
• Clinical Neuroscience, CAMH

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Objectives

1. To review the main physiological and
   pharmacological aspects of nicotine use, abuse,
   and dependence.
2. To discuss the different treatments available for
   nicotine dependence.

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Cigarette Smoking (Statistics)

• 47 worldwide
• 47 men
• 12 women
• 25 North America
• 1/3 - 1/2 of adolescents daily smoking
• 15 - 25 success rate to quit smoking
• Spontaneous quit rates in adults 6-7

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Costs of Tobacco Dependence

• 30 (males) and 17 (females) of all cancer
  deaths in Canada are due to smoking.
• Over 25 of cancer burden in Canada is
  attributable to lung cancer.
• 80 - 90 of lung cancers are directly
  attributable to smoking
• Smoking is also directly linked to
• Diabetes
• Heart disease
• Stroke
• Respiratory diseases
• CV disease

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Factors Associated With Smoking

• Biological
• hereditary, psychiatric, psychological
• Environmental
• parties, bars
• Social predisposition
• family, friends, cultural
• Easy access
• Socially acceptable?
• Peer pressure

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Factors
ENVIRONMENT
VECTOR
HOST
AGENT
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• Release of catecholamines increasing sympathetic
  tone (GI motility, cardiac stimulation),
  arginine-vasopressin, beta endorphins, ACTH,
  cortisol, GH, PL, etc.
• Enhanced memory, task performance, concentration,
  attention, and anxiety reduction.

?
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• Clinical conditions associated with smoking
• Respiratory
• Cardiovascular
• Comorbidity
• Psychiatric disorders
• Schizophrenia, depression, anxiety
• Other drugs of abuse
• Alcohol abuse/dependence

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Nicotine

• Psychoactive drug contained in tobacco
• Likely responsible for the addictive properties
  of cigarettes
• Self-administered by animals and humans
• Reinforcing and rewarding
• Following continuous administration the
  reinforcing effects of nicotine become prominent
  and the control over its use is lost

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• Nicotine content in cigarettes
• 6 11 mg (1-3 mg are absorbed)
• Pack a day 20 40mg
• Smokers adjust their nicotine intake
• High yield nicotine less cigarettes
• Low yield nicotine more cigarettes

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Pharmacology of Nicotine

• Absorption
• Buccal and nasal mucosa, skin, GI tract
• Blood flow, membrane permeability, surface area,
  and pH
• Other factors known to modify the rate of
  absorption
• Degree and depth of inhalation
• Number, duration, and volume of puffs
• Use of a filter
• Number of cigarettes smoked
• Time spent smoking each cigarette

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Peak nicotine concentrations are reached after
completion of cigarette smoking

• Distribution
• 19 seconds to reach the brain
• Half-life 2 hours
• Metabolism and elimination
• Liver and kidneys
• Main metabolite cotinine (70 - 80)
• CYP 2A6

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Pharmacokinetics of Nicotine After Smoking
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Neuropharmacology of Nicotine Dependence

• nAChRs
• Dopaminergic system (reward)
• Tolerance, physical dependence
• MAO A and B

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Cigarette
Smoking initiation
Nicotine
Reward Pathological learning
Smoking continuation
Active nAChRs
Dopamine release
Desensitized nAChRs
Acute tolerance
Inactive nAChRs
Chronic tolerance
Perpetuation of smoking behaviour
Smoking discontinuation
Hyper excitable nAChRs
Withdrawal
Increased no. of AChRs
Smoking relapse
Drive for the next cigarette
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Tobacco as a Drug of Abuse
DRUG ever used addiction risk
Tobacco 75.6 24.1 31.9
Alcohol 91.5 14.1 15.4
Illicit Drugs 51.0 7.5 14.7
Cannabis 46.3 4.2 9.1
Cocaine 16.2 2.7 16.7
Anxiolytics 12.7 1.2 9.2
Analgesics 9.7 0.7 7.5
Psychedelic 10.6 0.5 4.9
Heroin 1.5 0.4 23.1
Goodman and Gilman, 2001
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Nicotine Withdrawal Syndrome

• ? Psychological
• Irritability
• Anxiety
• Aggressiveness
• Inability to concentrate
• Depressed mood

• ? Physical
• Difficulty sleeping
• Increased appetite
• Headache

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Drug (Nicotine) Dependence DSM IV Criteria

1. Inability to stop using the drug
2. Preoccupation about drug use
3. Use despite harmful consequences
4. Presence of symptoms accounting for brain
   adaptation resulting in persistence use of the
   drug
5. Use despite significant drug-related problems

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Fagerström Test for Nicotine Dependence
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(No Transcript)
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Treatments for Nicotine Dependence

• Behavioural Intervention Therapies
• Individual behavioural counseling
• Nicotine fading
• Aversion treatments
• Acupuncture
• Hypnosis

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• Nicotine Replacement Therapies
• Patch (7, 14, 21, 22mg) 6-12 wks
• Gum (2 and 4mg) 8-12 wks
• Inhaler (4mg/cartridge) 6 16/day 3-6 mo
• Nasal spray (1-2/hr 0.5mg each max 40mg/day)
  3-6mo
• Low yield cigarettes

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• Bupropion
• 150mg twice/day 8-12 wks
• Risk of seizures (gt300mg)
• Nortriptyline
• Clonidine
• Nicotine Blockade Therapy
• Mecamylamine
• Experimental approaches
• GABA agonists (vigabatrin)

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Factors Associated With Low Quitting Success Rate

• Comorbid psychiatric conditions
• Alcohol or substance abuse
• High nicotine dependence
• Lack of social support for quitting
• Low self-confidence in ability to quit

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Pharmacokinetics of NRT
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Treating Tobacco Dependence

• Smoking is a complex human behaviour
• Often takes several quit attempts before one is
  successful
• NRT is most successful when combined with
  supportive care.
• Lapse and relapse is very common.