Tobacco Addiction
Jack E. Henningfield, PhD
Johns Hopkins School of Medicine
Pinney Associates
 2007 Johns Hopkins Bloomberg School of Public Health
Addiction Terminology
Addiction: common term applied to maladaptive drug-seeking
behavior
 Equivalent to American Psychiatric Association (APA)/World
Health Organization (WHO) “dependence”
Dependence: APA refers to “nicotine,” while WHO refers to
“tobacco” amount delivered to the person
 2007 Johns Hopkins Bloomberg School of Public Health
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Addiction Terminology
Withdrawal: transient symptoms following abstinence when
physical dependence is present (i.e., neuroadaptation)
Tolerance: decreased response to repeated doses
Dependence, withdrawal, and tolerance can occur independently
Withdrawal and tolerance are neither necessary nor sufficient for
dependence
 2007 Johns Hopkins Bloomberg School of Public Health
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Cigarettes Are among the Most Addictive Drugs
Addiction risk following use and addiction in current users:
 Cigarettes > Cocaine > Opioids > Alcohol
Image source: adapted by CTLT from U.S. National Academy of Science, Institution of Medicine. (1999).
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Trajectory of Tobacco Use
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Tobacco Related Deaths
Image source: Jack Henningfield.
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Smoke for Nicotine; Die from Smoke
“Smoke for nicotine; die from smoke”—Michael A.H. Russell
Image source: Jack Henningfield.
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All Tobacco Products Are Deadly and Addictive
Image source: Institute for Global Tobacco Control.
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Up in Tobacco Smoke
Most cigarettes contain about 10 mg nicotine
Bioavailability: 10–40% typical dose is 1–3 mg nicotine per
cigarette, regardless of whether it is advertised as “light” or
“regular”
Tar (or TPM) comes from the burning (pyrolysis) of tobacco; the
particles in smoke are in the size range (< one micron) that enters
the lung
CO is a pyrolysis product; its half life varies with respiratory rate
but it is typically four to seven hours in expired air or COHb tests
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Quotes
“Free nicotine is absorbed more rapidly by the smoker than is
bound nicotine”
 RJR, Rodgman (1980)
“As the pH increases, the nicotine changes its chemical form so
that it is more rapidly absorbed by the body and more quickly gives
a ‘kick’ to the smoker”
 McKenzie (1976); Minn. Trial Exhibit 12,270
“AT [ammonia technology] is the key to competing in smoke
quality with PM [Philip Morris] world-wide”
 B&W, Johnson (1989)
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Quotes
Low tar cigarettes
 “Provide smokers with a choice and a reason not to
quit”— Brown & Williamson (1979)
 “. . . the effect of switching to low tar cigarettes may
be to increase, not decrease, the risks of smoking”—
BAT, Lee (1979)
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Light Cigarettes
“Light” cigarettes are more ventilated and more readily enable
compensatory smoking
Ventilation holes
 2007 Johns Hopkins Bloomberg School of Public Health
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Menthol Light Cigarettes
Product design and ingredients
(menthol) converge to
produce cooler, smoother
smoke
This is a deadly and deceptive
marketing ploy because the
cigarettes are as toxic as “full
flavor” cigarettes
Image source: Tobacco Documents Online. Permission granted for educational use.
 2007 Johns Hopkins Bloomberg School of Public Health
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The “Ultimate” Chemical Cocktail
Tobacco-delivered nicotine
 Most addictive
 Most toxic
 Explosively fast delivery
 Optimal particle size to deposit in the lung
 pH controlled
 Sensory “optimization”
 Chemical cocktail designed to addict
 Ammonia increases dose
 Acetaldehyde synergy
 “Smoothing” menthol
 MAO (monoamine oxidase) inhibiting effects
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Neurobiology of Nicotine and Other Drugs
Like other abused drugs, nicotine stimulates brain reward
pathways and increases dopamine in the nucleus accumbens in the
brain
Effects in the brain reinforce behavior, alter mood, and create a
need that did not exist prior to drug exposure
 2007 Johns Hopkins Bloomberg School of Public Health
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Other Effects Contribute to Tobacco Use
Reduces anxiety and relieves stress and boredom
Improves performance and attention or at least reverses
withdrawal deficits
Decreases appetite
Helps start car and answer phone?
The ubiquitous association of smoking with daily living leads to
powerful behavioral conditioning
 2007 Johns Hopkins Bloomberg School of Public Health
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Blood Nicotine Concentration
Nicotine levels fluctuate widely, beginning at low levels after
sleeping and rising throughout the day
Waking is accompanied by early signs of withdrawal—with stronger
cravings in more dependent smokers
Image source: Jack Henningfield.
 2007 Johns Hopkins Bloomberg School of Public Health
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Damaging Effects of Tobacco
Nicotine in the brain leads to addiction
Image source: Jack Henningfield.
 2007 Johns Hopkins Bloomberg School of Public Health
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Effects of Four Drugs on Dopamine Levels
Image sources: adapted by CTLT from (top left to bottom right) Ponberi, F. E., et al. (1996); Melega et al. (1995);
Tanda et al. (1997).
 2007 Johns Hopkins Bloomberg School of Public Health
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Nicotine Receptor Modulation
Nicotine receptor modulation produces cascading effects via
neurohormones
Image source: Jack Henningfield.
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Nicotine Receptors Upregulate
Nicotine receptors upregulate: reversibility in chronic smokers
unclear
Image source: Jack Henningfield.
 2007 Johns Hopkins Bloomberg School of Public Health
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Increased Receptors
Increased receptors associated with tolerance and dependence
Image source: Jack Henningfield.
 2007 Johns Hopkins Bloomberg School of Public Health
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Brain of Nonsmoker Versus Brain of Smoker
Nonsmoker
Autopsy studies comparing
smokers to nonsmokers
reveal up to 400%
increases in brain nicotine
receptors
Reversibility extent, time
course, and variability is
unclear
Text source: Perry, D., et al. (1999); Image source: Journal of
Pharmacology and Experimental Therapeutics. (1999).
 2007 Johns Hopkins Bloomberg School of Public Health
Prefrontal cortex
Temporal cortex
Smoker
Hippocampus
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Nicotine Withdrawal and Dysfunction of the Brain
Nicotine withdrawal is
associated with
dysfunction of the brain
and performance, but it
can be treated
Nicotine replacement
and other therapies are
available
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Withdrawal Can Be Treated
Source: adapted by CTLT from Synder, F. and Henningfield, J. (1998).
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Medications (2006)
NRTs
 Gum
 Lozenge
 Patch (several types)
 Nasal
 Oral “inhaler”
Nicotinic
 Varenicline
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Medications (2006)
In development
 Rimonabant
 Vaccines
 New nicotine replacement therapies (NRTs)
 New medications
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Advertisement
Image source: Tobacco Documents Online (TobaccoDocuments.org). Permission granted for educational use.
 2007 Johns Hopkins Bloomberg School of Public Health
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Brain Imaging Studies
Smoking, withdrawal, and evoked cravings affect brain function as
assessed by imaging techniques including PET and fMRI
Regional cerebral blood flow (rCBF)
fMRI: BOLD STUDY:
Severity of nicotine dependence
modulates cue-induced brain activity
in regions involved in motor
preparation and imagery.
Psychopharmacology.
Image source: Zubieta, et al. (2005); Smolka, et al. (2005). No permission granted.
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Summary
Nicotine is highly addictive, and it is most addictive when
delivered in the form of tobacco products
Nicotine affects receptors in the brain and causes addiction
People who try to give up tobacco are fighting biology
Health professionals need to address the physical side of addiction
Treatment of addiction and prevention of smoking should go hand
in hand
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