Nicotine & Tobacco Research (1999) 1, S143-S147

Behavioral and cognitive effects of smoking:

relationship to nicotine addiction

Stephen J. Heishman

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Nicotine addiction is an extremely complex process that involves biological, psychological, behavioral, and
cultural factors. Three factors that influence smoking and that are influenced by smoking are performance,
stress, and body weight. We know that if nicotine-addicted smokers are deprived of nicotine, attentional and
cognitive abilities can be impaired, and such deficits can be reversed if the person smokes or is given nicotine.
In nonsmokers and nondeprived smokers, nicotine enhances finger tapping, focused and sustained attention,
recognition memory, and reasoning. Stress results in increased smoking, but there is little empirical evidence
that smoking reduces stress. Stress reduction from smoking is likely the relief of withdrawaMnduced negative
mood that is experienced between cigarettes. Smokers weigh on average 3-4 kg less than nonsmokers, and the
weight-gain seen after quitting smoking also averages 3-4 kg. Changes in eating and energy expenditure are
responsible for the body weight changes seen during smoking cessation and relapse. We need to know the full
range of conditions under which nicotine affects behavior. The mechanisms by which stress functions to
maintain nicotine addiction are not well understood. We do not know what interventions are effective in
addressing the stress experienced during smoking cessation. Because no effective interventions have been
developed to prevent weight-gain after quitting, research should focus on the concern or perception of
weight-gain. We need to understand how and why body weight concerns vary across gender, age, and ethnicity
because of the implications for designing effective smoking-cessation programs.

Introduction these factors and the relationship between these factors

Nicotine can function as a reinforcer to maintain self-
administration behavior in humans and animals (Rose &
Corrigall, 1997), and the mesolimbic dopaminergic sys-
tem is one brain site mediating the reinforcing effects of
nicotine and other drugs of abuse (Corrigall, Franklin,
Coen, & Clarke, 1992; Pich et al., 1997). Although drug
reinforcement is the biobehavioral basis of all addictive
disorders, nicotine addiction in humans is an extremely
complex process that involves biological, psychological,
behavioral, and cultural factors, all of which interact to
maintain the repetitive and compulsive use of tobacco
products. Three such factors that influence smoking and
that, in turn, are influenced by smoking are perform-
ance, stress, and body weight. How smoking affects
Stephen J. Heishman, PhD, Clinical Pharmacology& Therapeutics
Branch, NationalInstituteon Drug Abuse, Baltimore,Maryland.
Correspondenceto: StephenJ. Heishman,PhD, Clinical Pharmacol-
ogy and TherapeuticsBranch,NIDAAddictionResearchCenter,5500
Nathan ShockDrive,Baltimore,MD 21224;Tel"(410)550-1547;FAX:
(410) 550-1849; Email: sheish@intra.nida.nih.gov
and nicotine addiction form the basis of this article.
Effects of smoking on performance
What we know
The literature on the direct effects of smoking and
nicotine on human performance is fraught with method-
ological problems that limit the conclusions that can be
drawn (Heishman, Taylor, & Henningfield, 1994). For
example, many studies purporting to show that nicotine
enhanced some aspect of performance actually demon-
strated reversal of withdrawal effects because subjects
reported to the laboratory after being tobacco-abstinent
overnight. If nicotine-addicted smokers are deprived of
nicotine, their attentional and cognitive abilities can be
impaired. Such deficits in cognitive performance caused
by nicotine deprivation can be reversed if the person is
allowed to smoke or if they are given some form of
nicotine (Parrott & Roberts, 1991; Snyder & Hen-
ningfield, 1989). In human laboratory studies, perform-

1462-2203/99/$20143-05 © 1999 US Government

S 144 BEHAVIORAL AND COGNITIVE EFFECTS OF SMOKING
ance impairment has been observed to occur within 4 h
of enforced tobacco deprivation (Snyder, Davis, & Hen-
ningfield, 1989). A real-world application of these data
is that commercial airline pilots are allowed to smoke in
the cockpit, although the passenger cabin is smoke-free.
The Federal Aviation Administration knows that nic-
otine withdrawal can interfere with the skilled perform-
ance necessary to fly an airplane.
We can address the issue of nicotine-induced per-
formance enhancement versus withdrawal relief in stud-
ies conducted with nondeprived smokers and
nonsmokers because such research participants do not
introduce the confound of nicotine withdrawal. How-
ever, the fact that smokers differ from nonsmokers on a
variety of genetic, personality, and environmental fac-
tors (Gilbert, 1995) suggests that nicotine may differen-
tially affect these groups. One of the most reliable
effects of nicotine in smokers and nonsmokers is to
enhance motor responses. Studies have shown that nic-
otine enhances the ability to finger tap rapidly and
speeds up motor reaction time in tests of focused
attention. More recent and limited evidence indicates
that nicotine can also enhance sustained attention,
recognition memory, and reasoning abilities (Bell, Tay-
lor, Singleton, Henningfield, & Heishman, 1999; Heish-
man, 1998). However, no studies, to my knowledge,
have reported genuine enhancement of sensory abilities,
selective attention, or learning.
Following a period of nicotine deprivation, such as
the first few days of a quit attempt, the experience of
impaired concentration and thinking can be a strong
motivating factor to smoke a cigarette to reverse these
deficits, and thus the addiction to nicotine is maintained.
Compared to withdrawal relief, nicotine's true enhance-
ment of performance is probably of secondary import-
ance in the maintenance of addiction because of the
modest and limited genuine enhancing effects of nic-
otine on human performance (Heishman, 1998; Heish-
m a n et aL, 1994).
W h a t w e need to k n o w
First, we should determine the full range of conditions
under which nicotine affects behavior. Attentional pro-
cesses have been studied extensively, whereas few stud-
ies have examined nicotine's effect on learning or other
cognitive abilities such as reasoning or decision-making.
Given the structural complexity of nicotinic cholinergic
receptors (Lindstrom, 1996) and their extensive distri-
bution in the central and peripheral nervous systems
(Lefkowitz, Hoffman, & Taylor, 1990), it would appear
that nicotine could produce different functional effects
depending on the aspect of human performance being
tested and the delivered dose of nicotine.
Relatively few studies have attempted to control or
manipulate the many environmental, psychological, and
biological variables that influence nicotine's behavioral
effects. For example, few studies have used behavioral
pharmacological principles to examine the effects of
nicotine on performance that is maintained by a re-
inforcement contingency condition. Further, few studies
have tested the hypothesis that nonsmokers respond
differently to the effects of nicotine than smokers by
administering nicotine to both groups of subjects. Fi-
nally, few studies have attempted to tease apart the
various components of a task to examine potential
differential mechanisms by which nicotine exerts its
effects.
Dose-response relationships are not known for most
of nicotine's performance effects. This is basic psy-
chopharmacological knowledge. Only a small minority
of laboratory studies have administered placebo and
multiple doses of nicotine to humans to determine
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whether the observed effect continues to increase fin-
early with increasing dose or whether a nonlinear func-
tion is observed. Even fewer studies have reported
nicotine plasma concentrations to understand the rela-
tionship between plasma levels and performance.
Clearly, we need more research before we can reach
definitive answers concerning the relation between de-
livered dose of nicotine and magnitude of performance
effect.
Finally, given our current knowledge, enhanced atten-
tion and cognition are unlikely to play a major role in
adolescents' decisions to begin smoking (Heishman et
al., 1994), but no studies have directly addressed this
critical question.
Effects of smoking on stress
W h a t we k n o w
Naturalistic and laboratory studies have shown that
stressful situations result in increased desire to smoke
and actual smoking (Perkins & Grobe, 1992; Pomerleau
& Pomerleau, 1991), but little empirical evidence exists
that smoking reduces stress. If smoking reduced stress,
then smokers should be less stressed than nonsmokers,
but surveys repeatedly indicate that smokers are m o r e
stressed than nonsmokers. Further, if smoking reduced
stress, then smokers should experience increased stress
when they quit, but studies have shown that individuals
report feeling less stress after they quit smoking. Based
on these data, Parrott (1998) has put forth the argument
that smoking directly causes stress, which is contrary to
the common notion that people smoke to relax and
reduce stress. An alternative view is that smokers are
genetically and environmentally predisposed to in-
creased stress and negative affect, and thus smoke to
self-medicate their unhealthy mood states (Gilbert,
1995). However, no clear evidence exists that smoking
produces true stress reduction in smokers compared to
nonsmokers.
In addicted smokers, nicotine deprivation (with-
drawal) is characterized by feelings of increased stress,
anger, and irritability (Hughes, Higgins, & Hatsukami,
1990). Regular smokers can even develop these nega-
tive mood states during the 30--45-min interval between

cigarettes. Thus, smokers may experience heightened
levels of stress through such negative mood states
during acute nicotine deprivation between cigarettes. As
with performance deficits, smoking can rapidly reverse
such negative moods caused by nicotine deprivation. As
a result, when smokers reach for a cigarette to 'calm
down' or reduce stress, they may be simply relieving
withdrawal-induced stress and negative mood states that
are experienced between cigarettes or during more pro-
longed periods of tobacco abstinence (Parrott, 1998).
What we need to know
As indicated above, the most compelling, current expla-
nation is that smoking decreases stress and negative
mood states through reversal of withdrawal effects,
rather than producing genuine reductions in stress (Par-
rott, 1998). However, certain conditions may exist under
which smoking enhances mood and reduces stress in the
absence of nicotine deprivation. If such conditions were
identified through systematic study, then nicotine could
be regarded as a beneficial resource, such that smokers
could control their mood and stress levels or enhance
their cognitive abilities. Warburton (1994) has been the
primary proponent of this resource model of nicotine's
effects. However, numerous well-designed studies have
shown that nicotine does not genuinely enhance per-
formance across all behavioral domains (Heishman et
al., 1994) or reduce stress (Parrott, 1998) in nonsmokers
or in smokers who are not deprived of nicotine.
The mechanisms by which stress functions to main-
tain addictive smoking behavior are not well under-
stood. Numerous psychological and biological changes
occur during periods of stress, and some of these
changes in normal functioning may serve to maintain
nicotine self-administration. One possible mechanism
involves the hypophyseal-adrenal axis, which regulates
the circulating levels of corticosteroids secreted by the
adrenal gland during periods of stress (Pomerleau &
Pomerleau, 1991). Studies have shown that stress and
nicotine cause increases in corticosteroids in both ani-
mals and humans. Pomerleau and Pomerleau (1990)
reported that nicotine produced less corticosteroid re-
sponse in humans when they were administered a syn-
thetic corticosteroid the night before the test session.
They also found that the stress- and nicotine-induced
increase in corticosteroid levels was additive. These
data suggested that elevated corticosteroid levels re-
suited in reduced sensitivity to nicotine and that in-
creases in smoking observed during stress may represent
an attempt to compensate for this decreased sensitivity
to nicotine. Recently, Malin and colleagues have re-
ported that naloxone (Malin, Lake, Carter, Cunningham,
& Wilson, 1993) and an antiopiate peptide (Malin et aL,
1996) precipitated an abstinence syndrome in nicotine-
dependent rats, suggesting that the endogenous opioid
system is involved in nicotine dependence and with-
drawal. Such biochemical changes caused by the inter-
action of stress and nicotine could play a role in any
NICOTINE & TOBACCO RESEARCH S 145
aspect of nicotine addiction, including initiation of
smoking, cessation, or relapse.
Finally, we need to know what interventions might be
effective in helping people deal with the stress experi-
enced during smoking cessation. During the first week
after quitting, abstinent smokers typically experience
increased emotional stress and anxiety. Hughes et al.
(1990) reported that negative mood states returned to
baseline within 2 weeks and continued to decrease with
time. In contrast, a recent study found that, when the
effects of selective attrition and repeated measurement
were controlled, increases in negative affect did not
return to pre-quit baseline or to a smoking control group
after 30 days of tobacco abstinence (Gilbert et aL,
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1998). Research should focus on pharmacological and
nonpharmacological ways to help people cope with the
increased stress and negative moods experienced during
nicotine withdrawal. The recent report of bupropion as
a successful treatment for smoking cessation may be
explained, in part, by its ability to alleviate nicotine
withdrawal-induced negative affect (Hurt et aL, 1997).
Such pharmacological interventions coupled with inten-
sive behavioral counseling could significantly enhance
smoking cessation efforts.
Effects of smoking on body weight
What we know
An inverse relationship exists between smoking and
body weight. Smokers weigh on average 3-4 kg less
than nonsmokers, and the weight-gain reliably seen after
quitting smoking also averages 3-4kg (Klesges,
Meyers, Klesges, & LaVasque, 1989). Individuals who
smoke most heavily gain the most weight after quitting.
When individuals relapse after quitting smoking, their
weight returns to levels seen before quitting (Perkins,
1993). Thus, smoking clearly helps control body weight.
Evidence indicates that concerns over weight-gain,
rather than weight-gain itself, contribute to continued
smoking and appear to deter quit attempts, especially
among women (French & Jeffery, 1995; Perkins,
Levine, Marcus, & Shiffman, 1997). No direct evidence
exists that preventing weight-gain after quitting smok-
ing will increase cessation rates (Perkins, 1993).
Changes in energy intake (eating) and energy expen-
diture are responsible for the body weight changes seen
during smoking cessation and relapse. These changes in
body weight are mediated by nicotine because animal
studies have shown that nicotine decreases food intake
and increases energy expenditure in a dose-dependent
manner (Grnnberg, 1990). In humans, nicotine functions
as an appetite suppressant, and this property of nicotine
has been effectively used by the tobacco industry in its
marketing strategies toward women (Pierce, Lee, &
Gilpin, 1994). Eating increases during the first few
weeks after quitting smoking, and there is an increased
preference for sweets and carbohydrates. This prefer-
ence for sweets and carbohydrates may be mediated by
S 146 BEHAVIORAL AND COGNITIVE EFFECTS OF SMOKING
changes in levels of insulin and the neurotransmitter
serotonin, both of which are affected by nicotine (Grun-
berg, 1990). This increased food intake is mainly re-
sponsible for the weight-gain seen after quitting.
The two factors primarily influencing energy expen-
diture are metabolic rate and physical activity. The role
played by metabolic rate in body weight changes during
nicotine addiction and smoking cessation is not as clear
as that for energy intake; animal studies have yielded
inconsistent results (Grunberg, 1990). In humans, smok-
ing causes a modest acute increase in metabolic rate that
is repeated with each cigarette; however, chronic
changes in metabolic rate are not associated with smok-
ing or quitting (Perkins, 1993). There is no evidence
that smoking is associated with increased physical ac-
tivity, which would help keep weight down, or that
smoking cessation results in decreased activity, which
would encourage weight-gain (Grunberg, 1990). In fact,
the opposite may be true. When people stop smoking,
they tend to become more physically active than when
they smoked. Thus, physical activity does not appear to
play a role in either nicotine's control of body weight or
weight-gain after smoking cessation.
W h a t we need to k n o w
Because no effective interventions have been developed
to prevent weight-gain after quitting, research should
focus on the concern or perception of weight-gain.
Perkins et aL (1997) have begun to evaluate the effec-
tiveness of an adjunct intervention to a basic smoking
cessation program that employs cognitive-behavioral
treatment of inappropriate perceptions of weight-gain
during cessation and undue emphasis on a modest
weight-gain relative to the substantial health benefits
achieved from quitting smoking. Another treatment ap-
proach would be to focus the intervention solely on
smoking cessation and not devote any effort to weight-
control issues. The rationale with this approach is that
combining two forms of intervention--smoking cess-
ation and weight control requires a significant behav-
ioral change in two areas and thus is too complex and
challenging for individuals to accomplish successfully.
Weight-control concerns would be addressed after sev-
eral months of successful abstinence from smoking.
Results of this treatment evaluation study will provide
important information regarding the utility of adjunct
weight-control interventions in women who are con-
cerned about gaining weight during smoking cessation.
Such interventions may also provide greater understand-
ing of the psychological and biological mechanisms
underlying the effects of smoking and cessation on body
weight, especially regarding energy expenditure.
The importance of body weight concern appears to
vary across gender, age, and ethnicity. For example,
high school women who reported wanting to be thin,
who had tried to lose weight during the past year, and
who reported eating-disorder symptoms were twice as
likely to smoke as other women. The same relationship
did not exist for high school men (French & Jeffery,
1995). Caucasian adolescent women report smoking for
weight control, whereas African-American adolescent
women typically do not. National survey data from high
school seniors indicated that smoking and use of diet
pills was 2-10 times lower in African-American women
compared with Caucasian women (French & Jeffery,
1995). Further, it is possible that younger women have
greater concern about weight control than older women.
These gender, age, and ethnicity associations need fur-
ther research because they have obvious implications for
designing and implementing effective smoking cess-
ation programs.
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Conclusion
Biological, psychological, behavioral, and environmen-
tal variables interact to lead individuals to initiate use of
tobacco products and to sustain their compulsive use by
addicted individuals. Three variables that function in
complex ways to maintain nicotine addiction are per-
formance, stress, and body weight. The mechanisms by
which smoking and tobacco deprivation affect these
variables continue to be studied and identified. When
individuals attempt to quit smoking, they typically ex-
perience decrements in attention and cognition, in-
creased stress and negative mood, and weight-gain.
Smoking cessation treatment efforts will be enhanced to
the extent that effective interventions can be developed
for these unwanted effects of withdrawal.
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