Chapter 8 
Pharmacology and IVIarkers: Nicotine 
Pharmacology and A^ddictive Effects 
Jack E. Henningfield and Leslie M. Schuh 
INTRODUCTION Dosing characteristics of cigarette brands are estimated using 
machines that smoke representative cigarettes from each brand according 
to a protocol termed the Federal Trade Commission (FTC) method (Peeler, 
this volume; Pillsbury, this volume). This technology and methodology 
provide tar- and nicotine-dosing estimates of cigarettes that are misleading 
to consumers and do not accurately predict what level of tar and nicotine 
intake consumers will obtain by smoking a given brand of cigarettes 
(Henningfield et al., 1994). An understanding of the dependence-producing 
and other behavior-modifying effects of cigarette smoke is necessary to 
understand why the FTC method is a poor predictor of the nicotine, tar, 
and carbon monoxide levels people obtain from cigarettes. Cigarette 
smoking behavior is influenced by nicotine dose, and smokers tend to 
maintain nicotine intake within upper and lower boundaries (Kozlowski, 
1989). In brief, nicotine produces dose-related tolerance, physical 
dependence, and discriminative effects (i.e., effects that people can feel, 
which modify mood and physiology), and smokers change their behavior 
in response to these effects. Unlike human smokers, machines are not 
nicotine dependent, nor do they modify their behavior based on the flavor 
of the smoke. 
The FTC method was developed in the 1960's to provide a relative 
ranking of nicotine, tar, and carbon monoxide yields from various cigarettes 
(Peeler, this volume; Pillsbury, this volume). This ranking has provided 
consumers with the false sense that they can tell precisely the amount of 
these substances they will obtain from a given cigarette. Since the 1960's 
there have been many advances in the understanding of nicotine and 
smoking behavior that can be useful in reforming this methodology. This 
chapter provides an overview of relevant research, including (1) physiological 
and behavioral pressures to sustain nicotine intake; (2) the relationship 
between smoking and nicotine dose; (3) determinants of compensatory 
behavior, including the role of nicotine and other factors, such as flavor; 
and (4) measurement of smoking and nicotine intake. 
CIGARETTE 
SMOKING AS 
DRUG DEPENDENCE 
Addiction Severity 
Several findings bear on the issue of the strength of dependence 
on cigarettes. Although 70 to 90 percent of smokers are 
interested in quitting, only one in three succeeds before age 65 
(Fiore, 1992). There is good and bad news about coronary 
bypass surgery and even a lung removal. The good news is 
that these traumatic events are among the most powerful incentives to quit 
smoking. If one intervenes with patients who undergo these procedures, 
about one-half of them quit. However, the bad news is that the other half 
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