This document summarizes information about tobacco dependence and its treatment. It discusses how tobacco use impacts oral health and causes diseases. Tobacco dependence is classified as an addiction in diagnostic manuals. Treating tobacco dependence through counseling and pharmacotherapy is cost-effective for improving health outcomes. Combining nicotine replacement therapy with exercise or other adjuncts can help increase smoking abstinence rates, especially in women. Future areas of research include developing more effective behavioral treatments and new pharmacotherapies like nicotine vaccines.

1. Tobacco Dependence
and Its Treatment
Taru Hannele Kinnunen, PhD
Harvard Medical School
Harvard School Dental Medicine
Department of Oral Health Policy and Epidemiology
Harvard Medical School Alumni Day Plenary
June 2006

6. Tobacco Use and
Oral Cavity
TOBACCO
USE
Pre-
cancerous
Lesions
Oral
Cancers
•Gingivitis
•Periodontitis
•Acute Ulcero-Necrotic Gingivitis
•Teeth colorations
•Halitosis
•Sense of taste/smell
•Chronic Sinusitis
Consequences
in implantology
Consequences in
wound healing

7. Tobacco Dependence –
a Chronic Syndrome
ICD-10: 17 Mental and behavioral
disorders due to use of tobacco
17.1 Harmful use
17.2 Dependence syndrome
17.3 Withdrawal state
DSM-IV-TR: Nicotine Use Disorder
305.1 Nicotine Dependence
292.0 Nicotine Withdrawal
Dental code
D1320 Tobacco counseling for the control
and provision of oral disease

8. Smoking in Perspective
• Kills more than 430,000 Americans each year
• 25% of adult Americans smoke
• 3,000 children and adolescents become
regular tobacco users every day
• Causes cancer, heart disease, stroke,
pulmonary disease, and adverse pregnancy
outcomes
• Adds $50 billion in direct health costs each
year
• One-third of all tobacco users in U.S. will die
prematurely

9. Health Consequences of
Smoking Cessation
• Smoking is number 1 preventable cause of
death
• Treating tobacco dependence
– cost-effective
– significant measure in primary and secondary
prevention
• Smoking cessation results in many positive
health consequences
– most immediately and substantially coronary
heart disease and other cardiovascular
diseases (CVD)
(USDHH. Women and smoking: A report of the Surgeon General 2001.),
(Benowitz 2003, Kinnunen Mustonen 2004)

10. Treatment after CHD:
Reduction of the Mortality Risk
39%
29%
23%
23%
15%
0% 5% 10% 15% 20% 25% 30% 35% 40% 45%
Smoking Cessation
Statins
Beta-blockers
ACE-Inhibitors
Aspirin
JAMA, 2003
BMJ, 2000
BMJ, 1999
Lancet, 2000
BMJ, 2002

11. Difficulty in Quitting
• 70% of tobacco users would like to quit
• Less than 10% succeed in a given year
• Long term or permanent abstinence
may be achieved after several
attempts.
• Only 5-10% tobacco users are not
nicotine dependent

12. Nicotine Dependence
Copyright © 2002, TK. All rights reserved.
• Physiological dependence
 neurobiology:
 neuromodulation and neuroadaptation
 genetics
 positive and negative reinforcment
 withdrawal
• Conditioning/Learning
 highly conditioned behavior
 20 cigarettes x 10 puffs= 200 repetitions
 slips, relapse
• Sensory aspect of smoking

13. Clinical Guidelines for TX
 Intensity: Dose-response
 Type: Individual/Group
 Content
• Problem solving/Skills
training
• Intra-treatment social
support
• Extra-treatment social
support
 First-line therapies:
• NRT (gum, patch, lozenge,
inhlaler, spray)
• BupropionSR*(Zyban,
Wellbutrin)
 Second-line therapies:
• nortriptyline
• clonidine
 Combination therapies
• NRT+NRT
• Bupropion SR + NRT
 New Therapies
• Varenicline (Chantix)
Counseling
Behavioral Tx
Pharmacological Tx

14. 1-year Abstinence in Studies with
NRT and Behavioral Counseling
0
20
40
60
80
100
%Abstinent
1-week 16-weeks 1-year
Ex_NicGum CG_NicGum NicGum
0
10
20
30
40
50
60
70
80
90
100
1-week 16-week 1-year
NicGum
1992-1995
1999-2002
(Garvey & Kinnunen, NIDA)
(Kinnunen, NIDA)

15. From Tobacco Plant to
Cigarettes

16. Nicotine Dependence
self-administration
withdrawal symptoms

17. Acute Exposure
of Nicotine
• Tobacco smoke contains
concentrated amounts of
nicotine
•Fast delivery to brain
•Stimulation and release
of Ach
• Modulation of other
neurotransmitters
•Neuromodulation

18. nicotine receptor
nAChR
nicotine molecules
from
tobacco smoke
Acetylcholine
ACh
Synapse

19. Acetylcholine
ACh
nAChR
Nicotine
Synapse
Cholinergic neuron
Dopaminergic neuron

20. Most Effects are Mediated
by Nicotinic Receptors
(nAChRs)
Subtype α4β2
17 subtypes (α4β2, α7)

21. Minutes
Increaseinnicotineconcentration
(ng/ml)
Cigarette
Gum 4mg
Gum/ Lozenge 2mg
Inhaler
Nasal spray
Patch
5 10 15 20 25 30
0
2
4
6
8
10
12
14
Plasma Nicotine Concentrations
for Smoking and NRT
Source: Balfour DJ & Fagerström KO. Pharmacol Ther 1996 72:51-81.

22. Individualizing Treatment Double
Blind Placebo Controlled Study
Individualized Treatment
50%
Nicotine
Replacement
21 mg
Nicotine
Patch
42 mg
Nicotine
Patch
100%
Nicotine
Replacement
Placebo
Patch
Garvey & Kinnunen
2001-2005 NIDA
Does 100%
replacement
of nicotine
using nicotine
patches lead
higher
abstinence
rates?

23. Potential Factors Impacting
Cotinine Levels Obtained from
Nicotine Patches
• Patch Dose
• Baseline Cotinine Level
• Level of Dependence
on Nicotine
• Pack years (packs/day
x no. of years smoked)
• Cigarettes per day
smoked
• Age
• Sex
• Race
• Body Mass Index
• Clearance (Baseline
cot./cigs per day)
• Type of cigarette
(Menthol/ NonMenthol)

24. 0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375
Days Post - Cessat ion
0
10
20
30
40
50
60
70
80
90
100
PercentAbstinent Abstinence Patterns by Treatment Group
100%
50%
0 mg
21 mg
42 mg
p = .05
Garvey et al., 2006

25. Improving Treatment
• Adjuncts to behavioral and pharmacological
treatments may be one solution
• Tailoring treatments to specific population
– > WOMEN
– Women more fearful of gaining weight
– Women report more often negative affectivity
and stress after quitting
– Depression and smoking cessation have a
strong association and depression is more
common among women

26. Aerobic Exercise and NRT
for Female Smokers - Study
DA12503-01_04 Kinnunen (1999-2003)
•sedentary smokers
•ages 18-55
•no cardiac Hx
•over 5 cigarettes/day
Equal Contact Group (n=56)
Wellness Counseling (2 x week)
3 wks prequit 16 wks postquit
Nicotine gum
Brief Counseling
Experimental Group (n=92)
Aerobic Exercise (2-3 x week)
3 wks prequit 16 wks postquit
Nicotine gum
Brief Counseling
Standard Care Control Group (n= 34)
_
Nicotine gum
Brief Counseling

27. 1-Year Smoking Abstinence
Cumulative Proportion Surviving (Kaplan-Meier)
Exercise and NRT Study
0 50 100 150 200 250 300 350 400 450
Time
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSu
Standard care
Exercise
Wellness
Exercise and Wellness groups were
significantly different (p<.05) from
the Standard Care group
Kinnunen et al, 2005, Noc Tobacco Res

28. Conclusions
• Exercise promoted smoking cessation beyond
standard care
• Exercise had favorable impact on mood
• Poor adherence to exercise regimen among
those who had:
 Higher nicotine dependence
 Higher body mass index
 Higher depression level
 Higher stress level
 Lower education
Korhonen, Kinnunen et al., 2005, Tob Induced Dis

29. Increasing Adherence to TX
• Optimizing settings
(home vs. facility)
• Reducing barriers
• Increasing adherence
with counseling
• Continuing NRT
• Mapping out CVD
risk profile better and
assessing harm reduction NIDA –DA12503

30. Future Directions
• Expanding and enhancing behavioral
treatments
– (Front-loaded counseling Garvey &
Kinnunen, NIDA)
• Discovering new and new combinations
of pharmacotherapy
• Immunotherapy – Nicotine vaccine
• Harm reduction

31. Nicotine Vaccine
• Nicotine vaccine is designed to elicit the
production of nicotine antibodies.
If someone smokes after being immunized, the
antibodies bind with nicotine molecules in the
bloodstream and prevent them from entering
the brain where nicotine receptors are located.
Previous research has shown that, since antibody
levels rise slowly, smokers lose the nicotine
reward gradually, avoiding withdrawal symptoms.

32. "Quitting smoking is easy.
I've done it a thousand times.“
- Mark Twain