Tobacco Addiction. Addiction Terminology. Jack E. Henningfield, PhD Johns Hopkins School of Medicine Pinney Associates

Transcription

1 Tobacco Addiction Jack E. Henningfield, PhD Johns Hopkins School of Medicine Pinney Associates 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 2 1

2 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 3 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). 4 2

3 Trajectory of Tobacco Use 5 Tobacco Related Deaths Image source: Jack Henningfield. 6 3

4 Tobacco Addiction: Jack E. Henningfield, PhD Smoke for Nicotine; Die from Smoke Smoke for nicotine; die from smoke Michael A.H. Russell Image source: Jack Henningfield. 7 All Tobacco Products Are Deadly and Addictive Image source: Institute for Global Tobacco Control. 8 4

5 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 9 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) 10 5

6 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) 11 Light Cigarettes Light cigarettes are more ventilated and more readily enable compensatory smoking Ventilation holes 12 6

7 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. 13 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 14 7

8 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 15 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 16 8

9 Tobacco Addiction: Jack E. Henningfield, PhD 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. 17 Damaging Effects of Tobacco Nicotine in the brain leads to addiction Image source: Jack Henningfield. 18 9

10 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). 19 Nicotine Receptor Modulation Nicotine receptor modulation produces cascading effects via neurohormones Image source: Jack Henningfield

11 Tobacco Addiction: Jack E. Henningfield, PhD Nicotine Receptors Upregulate Nicotine receptors upregulate: reversibility in chronic smokers unclear Image source: Jack Henningfield. 21 Increased Receptors Increased receptors associated with tolerance and dependence Image source: Jack Henningfield

12 Tobacco Addiction: Jack E. Henningfield, PhD 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). Prefrontal cortex Temporal cortex Smoker Hippocampus 23 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 24 12

13 Withdrawal Can Be Treated Source: adapted by CTLT from Synder, F. and Henningfield, J. (1998). 25 Medications (2006) NRTs Gum Lozenge Patch (several types) Nasal Oral inhaler Nicotinic Varenicline 26 13

14 Medications (2006) In development Rimonabant Vaccines New nicotine replacement therapies (NRTs) New medications 27 Advertisement Image source: Tobacco Documents Online (TobaccoDocuments.org). Permission granted for educational use

15 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. 29 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 30 15