2007 Johns Hopkins Bloomberg School of Public Health Tobacco Addiction Jack E. Henningfield, PhD...

2007 Johns Hopkins Bloomberg School of Public Health

Tobacco AddictionTobacco 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-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


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


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).


Trajectory of Tobacco Use


Tobacco Related Deaths

Image source: Jack Henningfield.


Smoke for Nicotine; Die from Smoke

“Smoke for nicotine; die from smoke”—Michael A.H. Russell



All Tobacco Products Are Deadly and Addictive

Image source: Institute for Global Tobacco Control.


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


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)


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)


Light Cigarettes

“Light” cigarettes are more ventilated and more readily enable compensatory smoking

Ventilation holes


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.


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


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


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


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



Damaging Effects of Tobacco

Nicotine in the brain leads to addiction



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).


Nicotine Receptor Modulation


Nicotine receptor modulation produces cascading effects via neurohormones


Nicotine Receptors Upregulate

Nicotine receptors upregulate: reversibility in chronic smokers unclear



Increased receptors associated with tolerance and dependence

Increased Receptors



Brain of Nonsmoker Versus Brain of Smoker

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 ofPharmacology and Experimental Therapeutics. (1999).

Temporal cortex

Prefrontal cortex

Hippocampus

Nonsmoker

Smoker


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


Withdrawal Can Be Treated

Source: adapted by CTLT from Synder, F. and Henningfield, J. (1998).


Medications (2006)

NRTs Gum Lozenge Patch (several types) Nasal Oral “inhaler”

Nicotinic Varenicline


Medications (2006)

In development Rimonabant Vaccines New nicotine replacement therapies (NRTs) New medications


Advertisement

Image source: Tobacco Documents Online (TobaccoDocuments.org). Permission granted for educational use.


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.

Brain Imaging Studies

Smoking, withdrawal, and evoked cravings affect brain function as assessed by imaging techniques including PET and fMRI

Image source: Zubieta, et al. (2005); Smolka, et al. (2005). No permission granted.


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

2007 Johns Hopkins Bloomberg School of Public Health Tobacco Addiction Jack E. Henningfield, PhD...

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