To alleviate the symptoms of withdrawal, smokers re-dose themselves throughout the day. This figure depicts the typical nicotine addiction cycle a cigarette smoker experiences on a daily basis.
Note to instructor(s): Orient the students to the following elements on this figure:
-The jagged line represents venous plasma concentrations of nicotine as a cigarette is smoked every 40 minutes from 8 am to 9 pm.
-The upper solid line indicates the threshold concentration for nicotine to produce pleasure or arousal.
-The lower solid line indicates the concentrations at which symptoms of abstinence (i.e., withdrawal symptoms) from nicotine occur.
-The shaded area represents the zone of nicotine concentrations (neutral zone) in which the smoker is comfortable without experiencing either pleasure/arousal or abstinence symptoms.
After smoking the first cigarette of the day, the smoker experiences marked pharmacologic effects, particularly arousal. No other cigarette throughout the day produces the same degree of pleasure/arousal. For this reason, many smokers describe the first cigarette as the most important one of the day. Shortly after the initial cigarette, tolerance begins to develop. Accordingly, the threshold levels for both pleasure/arousal and abstinence rise progressively throughout the day as the smoker becomes tolerant to the effects of nicotine.
With continued smoking, nicotine accumulates, leading to an even greater degree of tolerance. As a result, the smoker experiences greater withdrawal symptoms between successive cigarettes. Late in the day, each individual cigarette produces only limited pleasure/arousal; instead, smoking primarily alleviates nicotine withdrawal symptoms.
Cessation of smoking overnight allows resensitization of drug responses (i.e., loss of tolerance). Most dependent smokers tend to smoke a certain number of cigarettes per day (usually more than 10) and tend to consume 10–40 mg of nicotine per day to achieve the desired effects of cigarette smoking and minimize the symptoms of nicotine withdrawal (Benowitz, 1992).

Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437.

Slide is used with permission, Rx for Change: Clinician-Assisted Tobacco Cessation. Copyright © 1999-2007 The Regents of the University of California, University of Southern California, and Western University of Health Sciences. All rights reserved.