Nicotine DependenceNicotine Dependence

Laurie Zawertailo, PhD

Adjunct Research Scientist

Clinical Neuroscience, CAMH

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.

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%

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

Factors Associated With Smoking

• Biological hereditary, psychiatric, psychological

• Environmental parties, bars

• Social predisposition family, friends, cultural

• Easy access • Socially acceptable?• Peer pressure

Factors

ENVIRONMENT

HOST AGENT

VECTOR

• 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.

?

Clinical conditions associated with smoking:• Respiratory• Cardiovascular

Comorbidity:• Psychiatric disorders

Schizophrenia, depression, anxiety• Other drugs of abuse

Alcohol abuse/dependence

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

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

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

Distribution • 19 seconds to reach the brain• Half-life: 2 hours

Metabolism and eliminationLiver and kidneysMain metabolite: cotinine (70% - 80%)CYP 2A6

Peak nicotine concentrations are reached after completion of cigarette smoking

Pharmacokinetics of Nicotine After Smoking

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0 20 40 60 80 100 120 140

time (min.)

pla

sma

[nic

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Neuropharmacology of Nicotine Dependence

• nAChR’s

• Dopaminergic system (reward)

• Tolerance, physical dependence

• MAO A and B

Cigarette

Active nAChRs

Dopaminerelease

Smoking initiation

Desensitized nAChRs

Nicotine

Reward

Pathological learning

Inactive nAChRs

Acute tolerance

Smoking continuation

Hyper excitable nAChRs

Chronic toleranceSmoking

discontinuationWithdrawal

Drive for the next cigarette

Increased no. of AChRsSmoking

relapse

Perpetuation of smoking behaviour

Tobacco as a Drug of AbuseDRUG % 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

Nicotine Withdrawal Syndrome

Psychological• Irritability• Anxiety• Aggressiveness• Inability to

concentrate• Depressed mood

Physical

• Difficulty sleeping• Increased appetite• Headache

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

Fagerström Test for Nicotine Dependence

Questions Answers Points 1. How soon after you wake up do you < 5 minutes 3 smoke you first cigarette 6 - 30 minutes 2 31- 60 minutes 1 After 60 minutes 0 2. Do you find it difficult to refrain from Yes 1 smoking in places where is forbidden No 0 e.g. in church, at the library, in cinema, etc.? 3. Which cigarette would you hate most to The first one in 1 give up? the morning All others 0

4. How many cigarettes/day do you smoke? 10 or less 0 11-20 1 21-30 2 31 or more 3 5. Do you smoke more frequently during the Yes 1 first hours after waking than during the No 0 rest of the day? 6. Do you smoke if you are so ill that you Yes 1 are in bed most of the day? No 0

Treatments for Nicotine Dependence

Behavioural Intervention Therapies

Individual behavioural counseling

Nicotine fading

Aversion treatments

Acupuncture

Hypnosis

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

Bupropion150mg twice/day 8-12 wksRisk of seizures (>300mg)

Nortriptyline

Clonidine

Nicotine Blockade TherapyMecamylamine

Experimental approachesGABA agonists (vigabatrin)

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

Pharmacokinetics of NRT

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time (min.)

pla

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[nic

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cigarette

gum

patch

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.