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| Tobacco cigarette smoking
and patellar reflex depression
One hundred fifteen young men served as subjects to determine the
effects of smoking cigarettes of differing nicotine content on the
patellar reflex. Each volunteer smoked 2 of the same kind of cigarettes in
a 4 minute period with an interval of 25 minutes between. The patellar
reflex was elicited automatically every 2 seconds by a reflex hammer
attached to a solenoid. The reflex was recorded with the use of a strain
gauge transducer and the electromyogram of the ipsilateral quadriceps
femoris muscle. A negligible depression was produced by smoking a
nicotine-free lettuce cigarette. A low-nicotine tobacco cigarette showed
approximately 45 per cent depression within 5 minutes compared with a 67
per cent depression after smoking a high-nicotine cigarette. The
depression caused by the second cigarette was comparable in degree and
duration to the effect of the first cigarette. No accumulative or
tachyphylactic effect was observed. It is concluded that tobacco smoking
produces a remarkable, short-term depression of the human skeletal-motor
system. The depression of the patellar reflex seems to be related to the
nicotine content of the cigarette smoked.
Edward F. Domino, M.S., M.D., and Alona M. von Baumgarten, M.D.*
Ann Arbor, and Detroit, Mich.
Michigan Neuropsychophartnacology Research Program, Department of
Pharmacology, University of Michigan, Ann Arbor, and
Lafayette Clinic, Detroit
The report of the Advisory Committee to the Surgeon General of the
United States Public Health Service on "Smoking and Health"
summarizes evidence on this controversial subjects There is no general
agreement as to why some people continue to smoke. Surely it must
be because of various complex pharmacological and psychological
reinforcements. As neuropsychopharmacologists, our own bias prompts us to
seek various pharmacological reinforcements of tobacco smoking, especially
those related to the central nervous system. For some time we have
been concerned with delineating the central actions of nicotine and
tobacco smoking in animals. These studies have convinced us that some
of the most important actions of small amounts of nicotine as
present in tobacco smoke are on the central nervous system.
Although much is known about the actions of nicotine on
the central nervous system of animals, relatively little
is knowvn about the central effects of tobacco smoking in human
beings, Marked cardiovascular and gastrointestinal effects have been
reported. The effects of nicotine and smoking on the human central nervous
system are much less defined. Inasmuch as nicotine produces a dramatic
reduction of the patellar reflex of animals, probably as a result of a
direct action of the central nervous systems it would be of considerable
interest to know if this pharmacological effect can be produced in man by
small doses of nicotine as absorbed during cigarette smoking. Clark and
Rand2 have shown that the human patellar reflex is depressed by cigarette
smoking. In their study, cigarette smoking had a much more pronounced
effect in nonsmokers and light smokers than in heavy smokers. Smoking
cigarettes containing an amount of nicotine comparable to commercial
cigarettes (2.1 per cent) inhibited the patellar reflex in a significantly
greater number of subjects than did smoking cigarettes with a low nicotine
content (0.1 per cent). An independent unpublished observation, by one of
us some time ago, that tobacco smoking had a profound effect in reducing
electromyograin artifact during electrical recordings of brain wave
activity in anxious patients, prompted us to undertake a systematic study
of the effects of tobacco smoking on skeletal muscle tone. It has been
reported that cigarette smoking causes a dramatic but transient reduction
in skeletal muscle tone in spastic patients. In view of the fact that the
human patellar reflex is easily elicited and measured, it seemed an ideal
end point for determining at least one major effect of tobacco smoking.
This article reports some of the results obtained with Dermal volunteers
who smoked cigarettes of varying nicotine
content. |
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Methods
Subjects. The experiments were performed on 115
healthy men between 17 and 29 years of age. All of them were asked not to
smoke for 12 hours before the experiment. Those who did not comply were
excluded from testing. The subjects were classified as nonsmokers, light
smokers (1-3 cigarettes a day), moderate smokers (3-20 cigarettes a day),
and heavy smokers (more than 20 cigarettes a day). In 17 cases the same
subject was investigated on 3 different days in which a cigarette of
different nicotine content was used in a random fashion. The rest of the
subjects were tested with only one type of cigarette. Prior to the study a
complete medical examination was given to exclude subjects with physical
or mental abnormalities. Four subjects were rejected because of
hyporeflexia. Subjects taking drugs within 2 weeks of the experimental
sessions were also excluded. The experiments were carried out in the
morning. Most of the subjects had breakfast several hours before the
experiment.
Experimental procedure. The experiment
consisted in smoking 2 cigarettes with an interval of 25 minutes between.
The patellar reflex was elicited with a mechanical rubber-tipped hammer
and monitored before, during, and after smoking by recording
simultaneously the isometric contraction with a Grass Model FT 10 strain
gauge and the electromyogram of the quadriceps muscle by surface
electrodes attached to the overlying skin. An Offner polygraph was used
for recording.
Three different cigarettes with varying nicotine content were used.
These were lettuce cigarettes which contain no nicotine and tobacco
cigarettes with a nicotine content of 0.80 and 1.69 mg. per cigarettes In
the beginning of the experimental series before nicotine-free cigarettes
were available, sham smoking was performed by taking puffs from an
unlighted cigarette or by inhaling it through a cotton-filled glass tube.
A typical experiment consisted of a control period of 10 minutes during
which the subject relaxed in horizontal position with the use of pillows
to make him as comfortable as possible. Smoking was started after 10
minutes or later, when steady patellar reflex responses were obtained. The
subject was advised to smoke each cigarette in a series of deep inhaling
puffs within a period of 4 minutes. Each cigarette was smoked to
approximately 2.5 cm. butt length, The second cigarette was smoked 25
minutes after the first.
The patellar reflex was elicited mechanically every 2 seconds. The
hammer exerted a pressure of about 0.5 Kg. upon hitting the
patellar tendon. The knee joint was flexed to about 90 degrees during the
resting state. The distal part of the lower leg was connected by a chain
to the strain gauge. The surface electromyogam was recorded bipolarly with
Grass electroencephalogram electrodes. One electrode was placed
above the quadriceps muscle in the middle of the upper leg, the other one
was placed 1 cm. proximal to the patella. The ground electrode was
placed in the middle. An A.C. differential amplifier with a time constant
of 0.1 msec. and 100 microvolts per centimeter amplitude was used.
Evaluation of data. Since the amplitude of the
patellar reflex showed marked individual variation, all data were
transformed as percentage of control. Only experiments in which a
steady state of reflex responding, was maintained for at least 5 minutes
before tobacco smoking were included in these
studies. |
| Results
General observations. At the beginning of the
experiment, marked variability of the patellar reflex was observed. With
time, as the subject relaxed, a more constant reflex amplitude was
obtained. Frequently, slight habituation or accommodation of reflex
activity was observed. Several subjects showed an actual increment during
the first 10 minutes of recording. The experiments with sham smoking and
with nicotine-free cigarettes revealed that when a steady state was
reached within the first 15 minutes no further habituation or
accommiodation appeared during the following 60 minutes of
reflex recording.
The amplitude of the electromyogram of the quadriceps
femoris was highly correlated with the amplitude of the mechanical
response. Alteration of the respiratory pattern when smoking started led
to slight changes in reflex activity. In most cases, an early slight
facilitation of the patellar reflex was observed beginning almost
immediately after smoking. This facilitation appeared irrespective of sham
smoking, smoking nicotine-free cigarettes or smoking nicotine-containing
cigarettes. However, the facilitation was quite variable. Some
individuals showed an early slight depression
instead. The mean of 20 cases showed, an increase of
about 11 per cent reflex activity during the first 15 seconds after
beginning smoking.
Subjects who smoked nicotine-containing cigarettes
invariably obtained a marked depression of the patellar reflex as recorded
mechanically, as well as in the electroniyographic response as illustrated
in Fig. 1. A portion of the actual record from a typical subject is shown
to illustrate the response to 2 types of cigarettes. Following a
nicotine-containing cigarette, depression of the patellar reflex was
observed about 30 seconds after the initial facilitation (if there
was any). The depression of the patellar reflex was progressive and
reached its peak at the end of smoking. The depression was always steeper
during the first minute than during the last 3 minutes of smoking.
After smoking, the depression remained at the same level or increased
slightly for a period of 30 to 120 seconds. Following this period of
depression, progressive recovery was observed. The curve of recovery was
steeper within the first 10 minutes than later. Twenty-five minutes after
the end of smoking, the reflex response in all but one case returned
toward control levels.
When full recovery was obtained the subject was asked to smoke a second
cigarette of the same nicotine content. The induced depression of the
patellar reflex quickly reappeared and resembled closely the depression
following the first cigarette. The mean data of all subjects is
illustrated in Figs. 2 and 3 and Table 1.
Marked mean differences in the depression of the patellar reflex were
found according to the nicotine content of the cigarettes smoked.
Nicotine-free cigarettes caused no more depression than that of normal
habituation of the reflex during sham smoking. Cigarettes with a nicotine
content of 0.80 mg. produced about 45 per cent depression of the patellar
reflex. Cigarettes with a nicotine content of 1.69 mg. produced 67 per
cent depression of normal.
In view of the fact that heavy smokers show tolerance to nicotine, it
was of interest to determine the differential effects of smoking high
nicotine-containing cigarettes on non- and heavy smokers. Fifteen
nonsmokers were chosen on the basis that they could inhale. Most of them
had smoked but stopped for at least 6 months to as long as 3 years
previously. Seven smokers were chosen on the basis they smoked one pack or
more of cigarettes per day and were able to stop smoking 12 hours prior to
the experiment. The mean depression of the patellar reflex + SE for each
group of subjects was determined. Occasionally nonsmokers were observed
who showed a greater depression of their patellar reflex after the first
cigarette, but this was not a constant finding for all of them. The heavy
smokers, deprived of cigarettes for 12 hours, tended to show a greater
depression of their patellar reflex than the nonsmokers. The reason for
this was not apparent but might be related to the fact they inhaled much
better. Further studies are now in progress to elucidate this phenomenon.
There was no evidence that these deprived heavy smokers were more
resistant to high nicotine-containing cigarettes.
Side effects. Twenty-nine of the 115 subjects complained
about slight to moderate dizziness during smoking. Most of these were
nonsmokers, but even some of the habitual smokers felt uneasy because the
deep smoke inhalations in a relatively short period of time were somewhat
unusual. |
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Contents
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Cigarette Nicotine Content as a
Determinant of Human Smoking Behavior
T.L. GOLDFARB, M. E. JARVIK, and S. D. GLICK
Albert Einstein College of Medicine, New York
Received October 7, 1969
Summary. Measures of smoking rate and psychological
effects of cigarettes with varying nicotine content are made in 15
subjects. While subjects did perceive differences in strength and quality
of the experimental letttice cigarettes as compared to their own brands,
their smoking rates did not decrease differentially over the
nicotine gradient. The decrement in smoking due to the experimental
cigarettes persisted when subjects resumed smoking their own cigarettes.
However, the smoking that did occur in the absence of both tobacco and
nicotine indicates that the habit itself often exhibits functional
autonomy from the physiological effects of nicotine.
The possibility that there is something in tobacco which is rewarding
has been entertained ever since smoking was known. Since the discovery,
more than a century ago, that the most powerful pharmacologicol component
of tobacco was nicotine, the view has often been expressed that people who
use tobacco are seeking the physiological effects of this alkaloid.
Many studies have investigated the psychological and sociological
theories of smoking motivation, but few studies have attempted to
demonstrate that nicotine or some other component of tobacco is a prime
incentive. While Johnston (1942) and Lucchesi et al. (1967) found that
intravenous administration of nicotine did influence human smoking
behavior, only Finnegan et al. (1945) and Herxheimer et al.
(1967) studied the effects of actual cigarette smoking using varying
nicotine content as an experimental variable. Finnegan et al. concluded
from psychological reports that some subjects did notice differences in
nicotine content, and Herxheimer et al. determined that cigarettes of
different nicotine content did indeed produce varied physiological
reactions. These physiological effects, however, did not prove to be the
sole determinant of smoking behavior, since Finnegan's study showed little
correlation between tile number of cigarettes smoked daily and each
subject's psychological report of being satisfied or dissatisfied with low
nicotine cigarettes. |
| The present study was designed as a further test of the
hypothesis that nicotine content of cigarettes is an important factor in
smoking. Subjects' baseline smoking rate with their own brands of
cigarettes was compared to their rates when smoking specially prepared
lettuce cigarettes varying in nicotine content from zero to 2..2.5 mg
nicotine per cigarette. At the game time, comparisons were made of
psychological measures of satisfaction from their own brands versus the
experimental cigarettes. In this way, the present study attempted to
evaluate the relationship between smokers' perceived effects of cigarettes
and the physiological effects of varying amounts of nicotine.
Material and Method
Fifteen paid volunteers participated in this study. They ranged in age
from 20 to 43 and each had been smoking it least one package of cigarettes
per day for two years or more.
The subjects were divided into three groups of five members. During the
first week of the study, all subjects smoked their own brands of
cigarettes. A prepared card was supplied to be stored in each package of
cigarettes smoked, thus facilitating accurate record keeping. For each
cigarette, the time and day it was smoked was noted along with two
psychological ratings of the effect of that particular cigarette.
"Strength" was measured on a continuum of 0 (very weak) to 4 (extremely
strong); "quality" was rated from 0 (great satisfaction) to 4 (extreme
dissatisfaction). At the end of the week, these cards were collected along
with a form on which each subject summarized his psychological reaction to
the entire weeks smoking.
In each of the three following weeks, subjects received one of three
types of experimental cigarettes: 1. "regular" lettuce cigarettes
(non-nicotine), 2. lettuce cigarettes to which 2% of nicotine had been
added (1.26 mg/nicotine/cigarette) and 3. lettuce cigarettes with 3%
nicotinic added (2.25 mg/nicotine/cigarette). All subjects smoked each
type of cigarette for one week, however, the three groups received the
varieties in different order to control for possible interaction effects
and time factors. At the beginning of each experimental week, subjects
received an envelope containing 2 cartons of the prepared cigarettes in
white unmarked packages. They were instructed to smoke as many cigarettes
as they wished each day, but not to smoke any other brand. They were told
to keep a careful record of their smoking on the card forms and to
complete their subjective summary at the end of the week.
In the fifth, and last, week of the study, all subjects again smoked
their own brands and completed the rating forms, as they had in the first
week. |
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Results
The Table represents the mean number of cigarettes smoked by each
subject during each of the experiment weeks, and also summarizes the mean
smoking rates for each group as compared with the psychological ratings of
strength and quality. It should be noted that four subjects dropped out of
the experiment during the second week when they were required to begin
smoking the experimental cigarettes. Fortunately, these dropouts occured
fairly evenly such that four subjects remained in groups 1 and 3, and
three subjects remained in group 2.
As may be seen in this table, all groups showed a general decrease in
smoking rate for al types of experimental cigarettes, as compared to the
first weeks rate with their own brands. Since no significant differences
were found in rates of smoking, the three experimental cigarettes, the
data is presented according to the order in which each group received the
three varieties. Thus, the tendency may be seen of subjects to smoke
progressively fewer experimental cigarettes week by week, regardless of
nicotine content, and to end up smoking fewer of their own cigarettes than
during, the first week of the study.
The psychological measurements of strength show that most subjects
could detect that the nicotine content of the three experimental
cigarettes was different, thus causing the higher nicotine cigarettes to
taste stronger (t tests, p <0.05 for 0 vs. 2%; p <0.01 for 0
vs. 3%; p <0.05 for 2% vs. 3%). However, the strength estimates were
numerically very close, and group 3, which received the 3% nicotine
cigarettes first, continued to rate all the experimental cigarettes
stronger than their own brands.
The "quality" ratings show that no subjects liked the experimental
cigarettes more than their own brands, and indeed, all of the subjects
complained about the taste of the lettuce cigarettes throughout the
experiment. This aversiveness measure was generally higher for the
experimental cigarettes, whatever the nicotine content, than for the first
week with the subjects' own brands, although it was highest for group 3
which had also noted a higher strength measure, is indicated above. The
rating for the subjects' own brands in week 5 was higher for each of the
groups than in week 1 showing a decrease in satisfaction.
Discussion
These results indicate that subjects do perceive differences in
nicotine content of cigarettes but that the physiological effects of these
quantitative differences do not necessarily correlate with perceived
psychological effects. It should be noted that the problem of subjective
strength and quality discriminations is especially difficult, particularly
when it interacts with taste factors and subjects' craving for cigarettes.
This is a situation well known to workers in psychophysics who find it
necessary to use trained subjects for sensory discriminations. It may
explain the fact that larger differences in strength and quality were not
seen for the three experimental cigarettes, which, when compared to
commercially available brands, represent cigarettes lower in nicotine thin
any available (the non-nicotine variety), average in nicotine (1.26
mg/cigarette), and higher in nicotine (2.26 mg/cigarette) than any
available.
It is interesting to note that few subjects reported maximum
satisfaction levels when smoking, their own brands of cigarettes during
week 1. After having, smoked the experimental cigarettes for 3 weeks, most
subjects upon returning, to their own brands, showed a decreased rate of
smoking. They also found their own cigarettes somewhat stronger than
before and, on the whole, less satisfying. It may be that the aversive
quality of the experimental cigarettes generalized to the smokers' own
brands. Perhaps this procedure might offer a clue for curing smokers of
their habit. On, the other hand, the component of habit in human smoking
seems quite strong, especially when it is realized that after It least two
years of smoking, the subjects found even their own brands, at best
"moderately satisfactory" (1.0 on the quality scale). It should also be
noted that, even though they disliked the experimental cigarettes, all of
the subjects continued to smoke them it a high rate. This would indicate a
fair degree of functional autonomy of the smoking habit from nicotine.
Acknowledgments. This research was supported by Grant TH-1 from
the American Cancer Society.
The experimental lettuce cigarettes used in this study were provided by
Mr. Putzant C. Torigian of Bravo Smokes, Cliffside Park, New Jersey, whose
cooperation and encouragement helped make these experiments possible.
Analysis and nicotine determination of the experimental cigarettes was
performed by Fitelson Laboratories, New York.
References
Finnegan, J. K., Larson, P. S., Haag, H. B.: The role of nicotine in
the cigarette habit. Science 102, 94-96 (1945).
Herxheimer, A., Griffiths, R. L., Hamilton, B., Wakefield, M.:
Circulatory effects of nicotine aerosol inhalations and cigarette smoking
in man. Lancet 1067 11, 754-755.
Johnston, L. M.: Tobacco smoking and nicotine. Lancet 1042, 742.
Lucchesi, B. R., Schuster, C. R., Emley, G. S.: The role of nicotine as
a determinant of cigarette smoking frequency in man with observations of
certain cardiovascular effects associated with the tobacco alkaloid. Clin.
Phamacol. Ther. S, 789-796 (1967).
Dr. Murray E. Jarvik
Albert Einstein College of
Medicine
Yeshiva University
1300 Morris Park Avenue
Bronx,
N. Y. 10461,
U.S.A. |
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Contents
If you
Must Smoke
Lettuce Said Best
To Avoid
Cancer
MINNEAPOLIS (UPI) - If you'd rather live than take a chance on
dying prematurely of cancer you may consider smoking cigarettes made of
Iceberg lettuce in the future.
The lettuce cigarettes seem to be very safe, Dr. George E.
Moore, a cancer expert, said here Wednesday.
Moore said tests at the Roswell Park Memorial institute in
Buffalo, N.Y.--one of the world's leading cancer research institutes--with
lettuce cigarettes had been very satisfactory, but had been limited to
animals so far. Moore is the head of the institute.
Moore spoke at a news conference. He was in Minneapolis to
address the annual meeting of the Minnesota Academy of General
Practice.
Smoking is responsible for 45,000 or more premature
cancer-caused deaths In the United States each year, he said. He said
there are ways to cut the cancer danger of smoking, be sides the obvious
one to stop smoking and besides the future possibility of switching to the
lettuce cigarettes.
Even tobacco cigarettes, can be made safer. Moore said. He said
the cancer danger in smoking is primarily in the tar. This had been
established by experiments on animals, he said.
Moore said Roswell Park recently listed its research findings
on the amount of tar that gets through various brands of commercial
cigarettes. There is a big difference between brands, he said, adding that
some filter cigarettes allow more tar to go through an some non-filter
cigarettes.
Moore also talked about leukemia, calling it "the most lethal
form of cancer" but added there now appears to be some hope it can be
cured. |
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