Nicotine regulation and cigarette smoking A study was conducted to determine whether there is nicotine regulation in cigarette smoking. Tar levels, which often covary with nicotine manipulations, were controlled for by the use of nicotine in chewing gums. Nicotine in cigarettes was also used for pre loading . High nicotine cigarette pre loads were followed by longer latencies to the next cigarette than were the low nicotine cigarette preloads. High nicotine gum pre/oads were followed by less puffing on the subsequent cigarettes than were the low nicotine gum pre loads .
Lynn T. Kozlowski, Ph.D., Murray E. Jarvik, M.D., and Ellen R. Gritz, Ph.D. Middletown, Conn., and Los Angeles, Calif. Department of Psychology, Wesleyan University, Departments of Psychiatry and Pharmacology, University of California, Los Angeles, and Department of Psychosocial Medicine, Brentwood Veterans Administration Hospital
Nicotine regulation effects in cigarette smoking, when found, have usually been quite small, but of the same form: low nicotine administrations lead to less inhibition of smoking than do high nicotine administrations. Unfortunately, several studies have failed to find comparable effects of nicotine manipulations. 7 If heavy cigarette smoking is to be considered a nicotine "dependency," the presence of nicotine regulation needs to be established. Even if cigarette smoking is, among other things, some lesser type of nicotine-seeking behavior, nicotine regulation is also in need of clear verification. At least three studies that have demonstrated a nicotine regulation effect are unsatisfactory because of a contaminating covariate; tar levels increased directly with nicotine manipulations in Ashton and Watson, 2 Herman,6 and Schachter's* reports. At least two experiments that Supported by American Cancer Society Grant No. DT·16G. Received for publication Sept. 18. 1974. Accepted for publication Oct. 9. 1974. *Unpublished observations.
have controlled tar levels have failed to find nicotine regulation effects. 4, 5 An experiment testing the role of nicotine intake in cigarette consumption and controlling the contaminating variables of previous studies seemed warranted. It was hypothesized that if nicotine levels were regulated in cigarette smoking, high nicotine "preloads" would be followed by less smoking than low nicotine "preloads." Both cigarettes and a chewing gum containing nicotine were administered as "preloads." Since tar covaries with nicotine in the cigarette preloads, the purest test of a regulation effect is found by looking at the effect of nicotine level in all the nicotine gum conditions combined (a gum main effect). The gum used was similar to the gum developed by the Leo Company in Sweden. 3 Research in their laboratories has shown that after 20 minutes of average chewing, 91 % of the nicotine dose is released from the gum. Although the nicotine from the gum does get into the plasma, even the high nicotine (4 mg) gum yields plasma levels smaller than those from a typical cigarette (1.3 mg). This agrees with
93
94
Kozlowski, Jarvik, and Gritz
Armitage'sl work on the relative inefficiency of nicotine absorption through the oral mucosa from cigarettes. Pilot studies in our laboratories revealed that increasing the gum dose irritated the mouth and throat and caused borderline nausea, undesirable side effects. Except for the administration of nicotine gum, the procedure was based on that of Herman. 6 In this paradigm smokers are studied fairly naturalistically. Subjects do not know that the experiment concerns smoking or that smoking is being measured in any way, although subjects are preloaded with two levels of nicotine in cigarettes. The paradigm also includes several measures of smoking; for example, the number of puffs subsequent to preloads rather than the number of cigarettes, and latency to smoke the next cigarette. Method
Subjects. Subjects were known to be smokers from their responses on a Student Information Sheet that was circulated around Columbia University. The subjects were 56 undergraduates (32 males, 24 females). Fourteen subjects received only credit for their introductory psychology class; 42 subjects were paid $2.50. Subjects were balanced in each cell for sex and average daily consumption (ADC) of cigarettes. Mean ADC was 20.75, with a range of 1 to 60. They were all inhalers and had been smoking on the average 5.9 years. Overview
In order to conceal the fact that the experiment was about cigarette smoking, subjects were told that the experiment concerned the effects of' 'noise pollution" on the performance of a simple motor task. After determining a baseline of motor task performance, subjects received one of two levels of nicotine (high or low) in one of three modes of preload: (1) placebo gum and a nicotine cigarette (PlacGumNicCig); (2) nicotine gum and no cigarette (NicGum-NoCig); and (3) nicotine gum and a non-tobacco lettuce cigarette (NicGum-Bravo). Conditions (2) and (3) were included to test for the role of oral and handling factors in cigarette smoking. Subjects were then left alone for 30 minutes to undergo control auditory stimulation. During this time, 6 Marlboro brand ciga-
Clinical Pharmacology and Therapeutics
rettes were available ad lib. An observer recorded the time it took the subject to light up the first cigarette and other indices of nicotine consumption. Procedure
On arrival, subjects were asked to fill out a short Urban Background questionnaire (a diversion from the experiment). In order to take the subject's own cigarettes away from him, he was told that a harmless physiologic measure would be used during the experiment. The subject was required to empty his pockets (give up his cigarettes) in order to weigh and measure him. After being taken to the experimental room, the subject was told that the study concerned two things: (l) how physiologically stressful characteristic urban noises are and (2) how these noises affect the performance of a motor task. The urban noise stimulus was said to be a recording of loud city noises such as sirens, horns, and jackhammers. All subjects were informed that they had been assigned at random to the control condition and would be listening to a recording of "pleasant and soothing" chamber music. They were told that an electromyograph (EMG) would be used as an index of how stressful the noise was to them in particular. The motor task was a labyrinth maze-a commercially available parlor game, which consists of a flat platform that can be tipped, with a maze on its surface. The object of this task is to keep a metal ball from falling into any of a series of holes while rolling down the alleys of the maze. The score for a trial is the number of the hole into which the ball falls. The subject worked at the maze for the next 25 minutes to get a preauditory stimulus baseline of his performance. In reality, this time, plus the 10 to 15 minutes of instruction and questionnaire, was intended to produce at least 35 to 40 minutes of cigarette deprivation in which nicotine levels in the blood would have some time to decrease, even if the subject had smoked a cigarette just before coming to the experiment. The gum administration. After the maze period was finished, subjects were told that the jaw muscles provided the best area for measuring stress with an EMG and that a base-
Volume 17 Number I
line would have to be taken, since there were large individual differences in the way muscle tension reflected stress. The baseline EMG consisted of a controlled amount of exercise of the jaw muscles. A dummy electrode from a Beckman/Offner dynograph was attached to the subject's cheek. Subjects were asked to chew some gum at the rate of 1 chew every 2 seconds for 5 minutes. The high nicotine gum contained 4 mg of nicotine; the low nicotine gum contained 1 mg of nicotine. A timer generated a click at this rate and subjects were instructed to chew once every time they heard the click. After the EMG baseline readings the experimenter took an apparent break, while he waited to take one more quick EMG without the gum being chewed. The experimenter used this time to tell the subject what he was to do during the music listening period. By the end of this break, all manipulations were completed. The manipulations. Each manipulation took place in two parts: (1) either placebo or high or low nicotine gum was administered during the EMG baseline period, and then (2) either a high or low nicotine tobacco cigarette, a non-tobacco lettuce cigarette (Bravo brand), or no cigarette was administered during the break. An observer watching through a one-way mirror noted the number of puffs the subjects took on the preload cigarette. Placebo gum and nicotine cigarettes. These conditions consisted of placebo gum in the EMG baseline session and either high (1.3 mg nicotine, 19 mg tar) or low (0.3 mg nicotine, 14 mg tar) nicotine cigarettes during the break. To administer the cigarettes, the experimenter produced a pack of cigarettes containing only 2 remaining cigarettes (both either high or low nicotine), took a cigarette himself, and offered a cigarette to the subject. A Rothman brand pack was used for the experimental cigarettes, since it was a rare brand in New York City. Nicotine gum and no cigarette. Low (1 mg) or high (4 mg) nicotine gums were administered in the EMG baseline session. No cigarette of any kind was offered during the break. The subject was engaged in a conversation similar to that which took place in the preceding conditions. Nicotine gum and Bravo. The same low and high nicotine gums comprised the nicotine ma-
Nicotine regulation and smoking
95
nipulations. The non-nicotine lettuce cigarettes were used in their own (Bravo) packs during the break. The free-smoking period. After the break, the second EMG reading was taken without gum being chewed. In a reminder of what they were to do during the music-listening period, subjects were told to remain seated, relax as much as possible, and listen to the music. The experimenter then said, ''I'll leave you some cigarettes in case you care to smoke." The experimenter produced a full pack of Marlboro brand cigarettes from a desk drawer, left 6 cigarettes in a clear plastic dish that had been on the desk at which the subject was seated, and left a pack of matches. As the experimenter opened the door to leave, he reminded the subject that he would be back in 30 minutes at the end of the music-listening period. The measures. When the experimenter closed the door behind him, the observer, watching through the mirror, started a timer to begin the 30-minute free-smoking period. Latency to the first cigarette was measured from the start of this period. The observer also noted the puff-times (time in which the cigarette was glowing while being puffed) during the freesmoking period. When the free-smoking period was over, the experimenter returned, revealed that the experiment was essentially over, and that it had been about something other than what had been said. The experimenter asked the subject if he had any idea what the experiment was about and then debriefed the subject thoroughly. Results
The effects of nicotine levels. Latency. Planned comparison F tests showed that subjects did light up sooner after a low nicotine cigarette than after a high nicotine cigarette (F(l,36) = 4.54, p < 0.05). Thus a nicotine regulation effect did occur (Table I). The test for a gum main effect was not possible for the latency measure. The variances in the NicGum-NoCig cells were too discrepant from those of the other conditions to permit their inclusion in an analysis of variance (F max test, p < 0.01). The nicotine level effect was tested separately for the NicGum-NoCig
96
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Clinical Pharmacology and Therapeutics
Table I. Latency in minutes to the first cigarette
Table ll. Total puff-time in seconds Mode of preload
Mode of preload Nicotine level
PlacGumNicCig
High
14.83 * (n
= 10)
4.73*
Low (n
= 10)
NicGumNoCig
7.95 (n
=
10)
4.92 (n = [0)
0.85 (n = 8)
0.12 (n
= 8)
*p < 0.05.
cells. There was possibly a slight tendency for subjects to smoke sooner after the low NicGumNoCig than after the high NicGum-NoCig (t(14) = 1.21, P < 0.20). The planned comparison F test showed that the high and low NicGumBravo conditions were not significantly different (F(1,36) = 0.410). Puff-times. PUff-time, the time for which the cigarette was glowing while being puffed, is the most sensitive index of nicotine consumption during the free-smoking period. Total puff-time in the free-smoking period showed that differential nicotine levels in cigarettes did not influence significantly the total puff-times (F(1,50) = 1.29), while the nicotine levels in the combined gum conditions had a sizable influence on the total puff-times. The high nicotine gums were followed by less puffing than were the low nicotine gums (F(l,50 = 4.26, P < 0.05) (Table II). Puff-time on the first cigarette is of interest because it indicates how soon in the free-smoking period the puff-time results were manifested and because the influence of some of the preloads may have been swamped by intervening cigarettes that are added in the total puff-time index. Neither the cigarette preloads (F(1,50) = 2.20, p < 0.25) nor the combined gum preloads (F(1,50) = 2.60, P < 0.25) resulted in differential puffing in their high and low nicotine conditions as measured by pufftime on the first cigarette. In addition, a related measure, number of puffs, correlates very highly (+0.90) with the puff-time measure and yields a very similar pattern of results and nearly identical statistical levels of probability.
Nicotine level High
PlacGumNicCig
15.03 (n = 10)
Low
22.05 (n
= 10)
NicGumNoCig
14.03 (n
(n = 8)
= 10)
(n = 8)
28.05 (n
[7.38
= 10)
22.25
For the nicotine gum conditions combined, the high nicotine gums were significantly different from the low nicotine gums (p < 0.05).
Discussion
In this study, the hypothesized self-regulation of nicotine intake was supported by the results; high nicotine preloads were followed by less smoking than low nicotine preloads. Nicotine in cigarettes affects the latency to the next cigarette, whereas it fails to affect the number of puffs in the free-smoking period. On the other hand, nicotine in gum fails to delay the taking of the next cigarette, but does decrease considerably the intake of nicotine as measured by total puff-time during the freesmoking period. Since the latencies in the NicGum-NoCig conditions are much shorter than those in the other cells (ps < 0.05, by X2 ), the tendency might be to conclude that the oral and handling components of cigarette smoking play a crucial role in smoking. However, for the subjects in the NicGum-NoCig conditions, the placing of the free-smoking period cigarettes constituted an offered rather than an additional cigarette, as in the other conditions. This "offered" cigarette was possibly a strong prod to short latencies. On the other hand, as mentioned previously, total puff-time during the free-smoking period was affected by nicotine in gum. It is possible that differential puffing on the preload cigarette might have accounted for the lack of a latency effect. Ashton and Watson 2 and Herman 6 have shown that smokers can adjust their nicotine intake on anyone cigarette by differential puffing. A subject may have maximized his low nicotine cigarette by taking many puffs, just as a subject may have taken a small number of puffs on the high nicotine preload cigarettes and received in effect a rather
Nicotine regulation and smoking 97
Volume 17 Number 1
small preload. In this study, however, there is no evidence of differential puffing on the preload cigarettes (t(l8) = 0.210). A few possible explanations come to mind for the differential effects of nicotine in cigarettes versus gum. Armitage 1 has shown in cats that the absorption of nicotine from cigarettes through the oral mucosa is a much slower and less efficient process than the absorption of nicotine through the lungs. The nicotine in gums is no doubt absorbed primarily through the buccal mucosa. The resultant slowness and inefficiency of absorption could be responsible for the failure to see latency effects with gum preloads. Perhaps plasma levels in even the high nicotine gum conditions were below a threshold that would delay the taking of an additional cigarette, but above a threshold that involves the duration of puffs taken on a cigarette. This threshold formulation suggests that a sizable effect of nicotine may be needed to affect latency measures. Possibly the gum effects were bimodal, or at least more diffuse and long-lasting than the cigarette nicotine effects, due to (I) the initial absorption of nicotine in the mouth and (2) a later absorption of swallowed nicotine in the gastrointestinal tract. Note in this regard that on the puff-time on the first cigarette measure, the cigarette conditions and combined gum conditions showed a similar nicotine effect, but, on the total puff-time measure, the gum effect becomes statistically significant. This suggests that the nicotine in gum had a longer duration of effect than the nicotine in cigarettes. Finally, the differential effects were probably not due to the tar covariate in the experimental cigarettes. Herman 6 found a greater tar differential than we did in this study, but a smaller difference in nicotine levels, and found no comparable latency effects. In sum, nicotine regulation in an acute ex-
periment was observed when a nicotine preload was administered either in the form of a cigarette or nicotine gum. For the cigarette condition, a high nicotine preload produced a significantly longer latency to smoke than a low nicotine preload. For the gum conditions, a high nicotine preload significantly shortened the total amount of free-smoking (puff-time duration) compared to a low nicotine preload. We thank Dr. Stanley Schachter for his assistance at all stages of this research and Kathleen M. Kozlowski for acting as observer.
References I. Armitage, A. K.: Some recent observations re-
2. 3. 4. 5.
6.
7.
8.
9.
lating to the absorption of nicotine from tobacco smoke, in Dunn, W., editor: Smoking behavior: Motives and incentives, Washington, 1973, V. H. Winston & Sons, pp. 83-92. Ashton, H., and Watson, D. W.: Puffing frequency and nicotine intake in cigarette smokers, Br. Med. J. 3:679-681, 1970. Ferno, 0.: A substitute for tobacco smoking, Psychopharmacologia 31:201-204, 1973. Finnegan, J. K., Larson, P. S., and Haag, H. B.: The role of nicotine in the cigarette habit, Science 102:94-96, 1945. Goldfarb, T. L., Jarvik, M. E., and Glick, S. D.: Cigarette nicotine content as a determinant of human smoking behavior, Psychopharmacologia 17:89-93, 1970. Herman, C. P.: The role of external and internal cues in the smoking behavior of light and heavy smokers, Unpublished doctoral dissertation, Columbia University, 1972. Jarvik, M. E.: The role of nicotine in the smoking habit, in Hunt, W. A., editor: Learning mechanisms in smoking, Chicago, 1970, Aldine Publishing Company, pp. 155-194. Jarvik, M. E.: Further observations on nicotine as the reinforcing agent in smoking, in Dunn, W., editor: Smoking behavior: Motives and incentives, Washington, 1973, V. H. Winston & Sons, pp. 33-50. Schachter, S.: Nicotine regulation in heavy and light smokers, Unpublished manuscript, Columbia University, 1973.
Lynn T. Kozlowski, Ph.D., Murray E. Jarvik, M.D., and Ellen R. Gritz, Ph.D. Middletown, Conn., and Los Angeles, Calif. Department of Psychology, Wesleyan University, Departments of Psychiatry and Pharmacology, University of California, Los Angeles, and Department of Psychosocial Medicine, Brentwood Veterans Administration Hospital
Nicotine regulation effects in cigarette smoking, when found, have usually been quite small, but of the same form: low nicotine administrations lead to less inhibition of smoking than do high nicotine administrations. Unfortunately, several studies have failed to find comparable effects of nicotine manipulations. 7 If heavy cigarette smoking is to be considered a nicotine "dependency," the presence of nicotine regulation needs to be established. Even if cigarette smoking is, among other things, some lesser type of nicotine-seeking behavior, nicotine regulation is also in need of clear verification. At least three studies that have demonstrated a nicotine regulation effect are unsatisfactory because of a contaminating covariate; tar levels increased directly with nicotine manipulations in Ashton and Watson, 2 Herman,6 and Schachter's* reports. At least two experiments that Supported by American Cancer Society Grant No. DT·16G. Received for publication Sept. 18. 1974. Accepted for publication Oct. 9. 1974. *Unpublished observations.
have controlled tar levels have failed to find nicotine regulation effects. 4, 5 An experiment testing the role of nicotine intake in cigarette consumption and controlling the contaminating variables of previous studies seemed warranted. It was hypothesized that if nicotine levels were regulated in cigarette smoking, high nicotine "preloads" would be followed by less smoking than low nicotine "preloads." Both cigarettes and a chewing gum containing nicotine were administered as "preloads." Since tar covaries with nicotine in the cigarette preloads, the purest test of a regulation effect is found by looking at the effect of nicotine level in all the nicotine gum conditions combined (a gum main effect). The gum used was similar to the gum developed by the Leo Company in Sweden. 3 Research in their laboratories has shown that after 20 minutes of average chewing, 91 % of the nicotine dose is released from the gum. Although the nicotine from the gum does get into the plasma, even the high nicotine (4 mg) gum yields plasma levels smaller than those from a typical cigarette (1.3 mg). This agrees with
93
94
Kozlowski, Jarvik, and Gritz
Armitage'sl work on the relative inefficiency of nicotine absorption through the oral mucosa from cigarettes. Pilot studies in our laboratories revealed that increasing the gum dose irritated the mouth and throat and caused borderline nausea, undesirable side effects. Except for the administration of nicotine gum, the procedure was based on that of Herman. 6 In this paradigm smokers are studied fairly naturalistically. Subjects do not know that the experiment concerns smoking or that smoking is being measured in any way, although subjects are preloaded with two levels of nicotine in cigarettes. The paradigm also includes several measures of smoking; for example, the number of puffs subsequent to preloads rather than the number of cigarettes, and latency to smoke the next cigarette. Method
Subjects. Subjects were known to be smokers from their responses on a Student Information Sheet that was circulated around Columbia University. The subjects were 56 undergraduates (32 males, 24 females). Fourteen subjects received only credit for their introductory psychology class; 42 subjects were paid $2.50. Subjects were balanced in each cell for sex and average daily consumption (ADC) of cigarettes. Mean ADC was 20.75, with a range of 1 to 60. They were all inhalers and had been smoking on the average 5.9 years. Overview
In order to conceal the fact that the experiment was about cigarette smoking, subjects were told that the experiment concerned the effects of' 'noise pollution" on the performance of a simple motor task. After determining a baseline of motor task performance, subjects received one of two levels of nicotine (high or low) in one of three modes of preload: (1) placebo gum and a nicotine cigarette (PlacGumNicCig); (2) nicotine gum and no cigarette (NicGum-NoCig); and (3) nicotine gum and a non-tobacco lettuce cigarette (NicGum-Bravo). Conditions (2) and (3) were included to test for the role of oral and handling factors in cigarette smoking. Subjects were then left alone for 30 minutes to undergo control auditory stimulation. During this time, 6 Marlboro brand ciga-
Clinical Pharmacology and Therapeutics
rettes were available ad lib. An observer recorded the time it took the subject to light up the first cigarette and other indices of nicotine consumption. Procedure
On arrival, subjects were asked to fill out a short Urban Background questionnaire (a diversion from the experiment). In order to take the subject's own cigarettes away from him, he was told that a harmless physiologic measure would be used during the experiment. The subject was required to empty his pockets (give up his cigarettes) in order to weigh and measure him. After being taken to the experimental room, the subject was told that the study concerned two things: (l) how physiologically stressful characteristic urban noises are and (2) how these noises affect the performance of a motor task. The urban noise stimulus was said to be a recording of loud city noises such as sirens, horns, and jackhammers. All subjects were informed that they had been assigned at random to the control condition and would be listening to a recording of "pleasant and soothing" chamber music. They were told that an electromyograph (EMG) would be used as an index of how stressful the noise was to them in particular. The motor task was a labyrinth maze-a commercially available parlor game, which consists of a flat platform that can be tipped, with a maze on its surface. The object of this task is to keep a metal ball from falling into any of a series of holes while rolling down the alleys of the maze. The score for a trial is the number of the hole into which the ball falls. The subject worked at the maze for the next 25 minutes to get a preauditory stimulus baseline of his performance. In reality, this time, plus the 10 to 15 minutes of instruction and questionnaire, was intended to produce at least 35 to 40 minutes of cigarette deprivation in which nicotine levels in the blood would have some time to decrease, even if the subject had smoked a cigarette just before coming to the experiment. The gum administration. After the maze period was finished, subjects were told that the jaw muscles provided the best area for measuring stress with an EMG and that a base-
Volume 17 Number I
line would have to be taken, since there were large individual differences in the way muscle tension reflected stress. The baseline EMG consisted of a controlled amount of exercise of the jaw muscles. A dummy electrode from a Beckman/Offner dynograph was attached to the subject's cheek. Subjects were asked to chew some gum at the rate of 1 chew every 2 seconds for 5 minutes. The high nicotine gum contained 4 mg of nicotine; the low nicotine gum contained 1 mg of nicotine. A timer generated a click at this rate and subjects were instructed to chew once every time they heard the click. After the EMG baseline readings the experimenter took an apparent break, while he waited to take one more quick EMG without the gum being chewed. The experimenter used this time to tell the subject what he was to do during the music listening period. By the end of this break, all manipulations were completed. The manipulations. Each manipulation took place in two parts: (1) either placebo or high or low nicotine gum was administered during the EMG baseline period, and then (2) either a high or low nicotine tobacco cigarette, a non-tobacco lettuce cigarette (Bravo brand), or no cigarette was administered during the break. An observer watching through a one-way mirror noted the number of puffs the subjects took on the preload cigarette. Placebo gum and nicotine cigarettes. These conditions consisted of placebo gum in the EMG baseline session and either high (1.3 mg nicotine, 19 mg tar) or low (0.3 mg nicotine, 14 mg tar) nicotine cigarettes during the break. To administer the cigarettes, the experimenter produced a pack of cigarettes containing only 2 remaining cigarettes (both either high or low nicotine), took a cigarette himself, and offered a cigarette to the subject. A Rothman brand pack was used for the experimental cigarettes, since it was a rare brand in New York City. Nicotine gum and no cigarette. Low (1 mg) or high (4 mg) nicotine gums were administered in the EMG baseline session. No cigarette of any kind was offered during the break. The subject was engaged in a conversation similar to that which took place in the preceding conditions. Nicotine gum and Bravo. The same low and high nicotine gums comprised the nicotine ma-
Nicotine regulation and smoking
95
nipulations. The non-nicotine lettuce cigarettes were used in their own (Bravo) packs during the break. The free-smoking period. After the break, the second EMG reading was taken without gum being chewed. In a reminder of what they were to do during the music-listening period, subjects were told to remain seated, relax as much as possible, and listen to the music. The experimenter then said, ''I'll leave you some cigarettes in case you care to smoke." The experimenter produced a full pack of Marlboro brand cigarettes from a desk drawer, left 6 cigarettes in a clear plastic dish that had been on the desk at which the subject was seated, and left a pack of matches. As the experimenter opened the door to leave, he reminded the subject that he would be back in 30 minutes at the end of the music-listening period. The measures. When the experimenter closed the door behind him, the observer, watching through the mirror, started a timer to begin the 30-minute free-smoking period. Latency to the first cigarette was measured from the start of this period. The observer also noted the puff-times (time in which the cigarette was glowing while being puffed) during the freesmoking period. When the free-smoking period was over, the experimenter returned, revealed that the experiment was essentially over, and that it had been about something other than what had been said. The experimenter asked the subject if he had any idea what the experiment was about and then debriefed the subject thoroughly. Results
The effects of nicotine levels. Latency. Planned comparison F tests showed that subjects did light up sooner after a low nicotine cigarette than after a high nicotine cigarette (F(l,36) = 4.54, p < 0.05). Thus a nicotine regulation effect did occur (Table I). The test for a gum main effect was not possible for the latency measure. The variances in the NicGum-NoCig cells were too discrepant from those of the other conditions to permit their inclusion in an analysis of variance (F max test, p < 0.01). The nicotine level effect was tested separately for the NicGum-NoCig
96
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Clinical Pharmacology and Therapeutics
Table I. Latency in minutes to the first cigarette
Table ll. Total puff-time in seconds Mode of preload
Mode of preload Nicotine level
PlacGumNicCig
High
14.83 * (n
= 10)
4.73*
Low (n
= 10)
NicGumNoCig
7.95 (n
=
10)
4.92 (n = [0)
0.85 (n = 8)
0.12 (n
= 8)
*p < 0.05.
cells. There was possibly a slight tendency for subjects to smoke sooner after the low NicGumNoCig than after the high NicGum-NoCig (t(14) = 1.21, P < 0.20). The planned comparison F test showed that the high and low NicGumBravo conditions were not significantly different (F(1,36) = 0.410). Puff-times. PUff-time, the time for which the cigarette was glowing while being puffed, is the most sensitive index of nicotine consumption during the free-smoking period. Total puff-time in the free-smoking period showed that differential nicotine levels in cigarettes did not influence significantly the total puff-times (F(1,50) = 1.29), while the nicotine levels in the combined gum conditions had a sizable influence on the total puff-times. The high nicotine gums were followed by less puffing than were the low nicotine gums (F(l,50 = 4.26, P < 0.05) (Table II). Puff-time on the first cigarette is of interest because it indicates how soon in the free-smoking period the puff-time results were manifested and because the influence of some of the preloads may have been swamped by intervening cigarettes that are added in the total puff-time index. Neither the cigarette preloads (F(1,50) = 2.20, p < 0.25) nor the combined gum preloads (F(1,50) = 2.60, P < 0.25) resulted in differential puffing in their high and low nicotine conditions as measured by pufftime on the first cigarette. In addition, a related measure, number of puffs, correlates very highly (+0.90) with the puff-time measure and yields a very similar pattern of results and nearly identical statistical levels of probability.
Nicotine level High
PlacGumNicCig
15.03 (n = 10)
Low
22.05 (n
= 10)
NicGumNoCig
14.03 (n
(n = 8)
= 10)
(n = 8)
28.05 (n
[7.38
= 10)
22.25
For the nicotine gum conditions combined, the high nicotine gums were significantly different from the low nicotine gums (p < 0.05).
Discussion
In this study, the hypothesized self-regulation of nicotine intake was supported by the results; high nicotine preloads were followed by less smoking than low nicotine preloads. Nicotine in cigarettes affects the latency to the next cigarette, whereas it fails to affect the number of puffs in the free-smoking period. On the other hand, nicotine in gum fails to delay the taking of the next cigarette, but does decrease considerably the intake of nicotine as measured by total puff-time during the freesmoking period. Since the latencies in the NicGum-NoCig conditions are much shorter than those in the other cells (ps < 0.05, by X2 ), the tendency might be to conclude that the oral and handling components of cigarette smoking play a crucial role in smoking. However, for the subjects in the NicGum-NoCig conditions, the placing of the free-smoking period cigarettes constituted an offered rather than an additional cigarette, as in the other conditions. This "offered" cigarette was possibly a strong prod to short latencies. On the other hand, as mentioned previously, total puff-time during the free-smoking period was affected by nicotine in gum. It is possible that differential puffing on the preload cigarette might have accounted for the lack of a latency effect. Ashton and Watson 2 and Herman 6 have shown that smokers can adjust their nicotine intake on anyone cigarette by differential puffing. A subject may have maximized his low nicotine cigarette by taking many puffs, just as a subject may have taken a small number of puffs on the high nicotine preload cigarettes and received in effect a rather
Nicotine regulation and smoking 97
Volume 17 Number 1
small preload. In this study, however, there is no evidence of differential puffing on the preload cigarettes (t(l8) = 0.210). A few possible explanations come to mind for the differential effects of nicotine in cigarettes versus gum. Armitage 1 has shown in cats that the absorption of nicotine from cigarettes through the oral mucosa is a much slower and less efficient process than the absorption of nicotine through the lungs. The nicotine in gums is no doubt absorbed primarily through the buccal mucosa. The resultant slowness and inefficiency of absorption could be responsible for the failure to see latency effects with gum preloads. Perhaps plasma levels in even the high nicotine gum conditions were below a threshold that would delay the taking of an additional cigarette, but above a threshold that involves the duration of puffs taken on a cigarette. This threshold formulation suggests that a sizable effect of nicotine may be needed to affect latency measures. Possibly the gum effects were bimodal, or at least more diffuse and long-lasting than the cigarette nicotine effects, due to (I) the initial absorption of nicotine in the mouth and (2) a later absorption of swallowed nicotine in the gastrointestinal tract. Note in this regard that on the puff-time on the first cigarette measure, the cigarette conditions and combined gum conditions showed a similar nicotine effect, but, on the total puff-time measure, the gum effect becomes statistically significant. This suggests that the nicotine in gum had a longer duration of effect than the nicotine in cigarettes. Finally, the differential effects were probably not due to the tar covariate in the experimental cigarettes. Herman 6 found a greater tar differential than we did in this study, but a smaller difference in nicotine levels, and found no comparable latency effects. In sum, nicotine regulation in an acute ex-
periment was observed when a nicotine preload was administered either in the form of a cigarette or nicotine gum. For the cigarette condition, a high nicotine preload produced a significantly longer latency to smoke than a low nicotine preload. For the gum conditions, a high nicotine preload significantly shortened the total amount of free-smoking (puff-time duration) compared to a low nicotine preload. We thank Dr. Stanley Schachter for his assistance at all stages of this research and Kathleen M. Kozlowski for acting as observer.
References I. Armitage, A. K.: Some recent observations re-
2. 3. 4. 5.
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lating to the absorption of nicotine from tobacco smoke, in Dunn, W., editor: Smoking behavior: Motives and incentives, Washington, 1973, V. H. Winston & Sons, pp. 83-92. Ashton, H., and Watson, D. W.: Puffing frequency and nicotine intake in cigarette smokers, Br. Med. J. 3:679-681, 1970. Ferno, 0.: A substitute for tobacco smoking, Psychopharmacologia 31:201-204, 1973. Finnegan, J. K., Larson, P. S., and Haag, H. B.: The role of nicotine in the cigarette habit, Science 102:94-96, 1945. Goldfarb, T. L., Jarvik, M. E., and Glick, S. D.: Cigarette nicotine content as a determinant of human smoking behavior, Psychopharmacologia 17:89-93, 1970. Herman, C. P.: The role of external and internal cues in the smoking behavior of light and heavy smokers, Unpublished doctoral dissertation, Columbia University, 1972. Jarvik, M. E.: The role of nicotine in the smoking habit, in Hunt, W. A., editor: Learning mechanisms in smoking, Chicago, 1970, Aldine Publishing Company, pp. 155-194. Jarvik, M. E.: Further observations on nicotine as the reinforcing agent in smoking, in Dunn, W., editor: Smoking behavior: Motives and incentives, Washington, 1973, V. H. Winston & Sons, pp. 33-50. Schachter, S.: Nicotine regulation in heavy and light smokers, Unpublished manuscript, Columbia University, 1973.
