tobacco control lec2.4 henningfield · 2013. 7. 12. · Tobacco Addiction: Jack E. Henningfield,...
Transcript of tobacco control lec2.4 henningfield · 2013. 7. 12. · Tobacco Addiction: Jack E. Henningfield,...
Tobacco Addiction: Jack E. Henningfield, PhD
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Tobacco Addiction
Jack E. Henningfield, PhDJohns Hopkins School of MedicinePinney Associates
2© 2007 Johns Hopkins Bloomberg School of Public Health
Addiction Terminology
Addiction: common term applied to maladaptive drug-seekingbehavior− 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
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Addiction Terminology
Withdrawal: transient symptoms following abstinence whenphysical 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 fordependence
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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 percigarette, regardless of whether it is advertised as “light” or“regular”
Tar (or TPM) comes from the burning (pyrolysis) of tobacco; theparticles in smoke are in the size range (< one micron) that entersthe lung
CO is a pyrolysis product; its half life varies with respiratory ratebut 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 isbound nicotine”− RJR, Rodgman (1980)
“As the pH increases, the nicotine changes its chemical form sothat it is more rapidly absorbed by the body and more quickly givesa ‘kick’ to the smoker”− McKenzie (1976); Minn. Trial Exhibit 12,270
“AT [ammonia technology] is the key to competing in smokequality 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 enablecompensatory smoking
Ventilation holes
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Menthol Light Cigarettes
Product design andingredients (menthol)converge to produce cooler,smoother smoke
This is a deadly and deceptivemarketing ploy because thecigarettes are as toxic as “fullflavor” cigarettes
Image source: Tobacco Documents Online. Permission granted for educational use.
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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 rewardpathways and increases dopamine in the nucleus accumbens in thebrain
Effects in the brain reinforce behavior, alter mood, and create aneed that did not exist prior to drug exposure
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Other Effects Contribute to Tobacco Use
Reduces anxiety and relieves stress and boredom
Improves performance and attention or at least reverseswithdrawal deficits
Decreases appetite
Helps start car and answer phone?
The ubiquitous association of smoking with daily living leads topowerful behavioral conditioning
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Blood Nicotine Concentration
Nicotine levels fluctuate widely, beginning at low levels aftersleeping and rising throughout the day
Waking is accompanied by early signs of withdrawal—with strongercravings in more dependent smokers
Image source: Jack Henningfield.
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Damaging Effects of Tobacco
Nicotine in the brain leads to addiction
Image source: Jack Henningfield.
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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).
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Nicotine Receptor Modulation
Image source: Jack Henningfield.
Nicotine receptor modulation produces cascading effects vianeurohormones
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Nicotine Receptors Upregulate
Nicotine receptors upregulate: reversibility in chronic smokersunclear
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Increased receptors associated with tolerance and dependence
Increased Receptors
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Brain of Nonsmoker Versus Brain of Smoker
Autopsy studies comparingsmokers to nonsmokersreveal up to 400%increases in brain nicotinereceptors
Reversibility extent, timecourse, and variability isunclear
Text source: Perry, D., et al. (1999); Image source: Journal ofPharmacology and Experimental Therapeutics. (1999).
Temporal cortex
Prefrontal cortex
Hippocampus
Nonsmoker
Smoker
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Nicotine Withdrawal and Dysfunction of the Brain
Nicotine withdrawal isassociated withdysfunction of the brainand performance, but itcan be treated
Nicotine replacementand other therapies areavailable
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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.
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Regional cerebral blood flow (rCBF)
fMRI: BOLD STUDY:Severity of nicotine dependencemodulates cue-induced brain activityin regions involved in motorpreparation and imagery.Psychopharmacology.
Brain Imaging Studies
Smoking, withdrawal, and evoked cravings affect brain function asassessed by imaging techniques including PET and fMRI
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 whendelivered 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 handin hand