Juliano Abnormal Psychology

Order Description
Write a two page article critique on the attached document
Experimental Evidence for a Causal Relationship Between Smoking Lapse
and Relapse
Laura M. Juliano
American University
Eric C. Donny, Elisabeth J. Houtsmuller, and
Maxine L. Stitzer
Johns Hopkins University School of Medicine
In this study, the authors prospectively evaluated the impact of a smoking lapse on relapse probability.
After 4 days of smoking abstinence, 60 smokers were randomly assigned to smoke 5 nicotine-containing
or 5 denicotinized cigarettes, or to remain abstinent (no lapse) during a 4-hr time period. Afterward,
smoking abstinence was encouraged with monetary incentives, and smoking behavior was tracked for 6
days. Relative to the no-lapse condition, exposure to either of the cigarette types more than doubled the
probability of subsequent smoking. Smoking outcomes did not differ between nicotine-containing and
denicotinized cigarettes. The data suggest that stimulus factors may play an important role in lapse to
relapse processes.
Keywords: smoking, lapse, relapse, denicotinized, nicotine
Relapse continues to be the most likely outcome of an attempt
to quit smoking. As many as 85%–90% of individuals who attempt
to quit return to regular smoking within 1 year (Baer, Kamarck,
Lichtenstein, & Ransom, 1989; Brandon, Tiffany, Obremski, &
Baker, 1990; Garvey, Bliss, Hitchcock, Heinold, & Rosner, 1992).
The relapse process begins with a single smoking episode, which
may appear at the outset to be a lapse or a slip. Although it is
possible that an individual could achieve long-term abstinence
despite having had a smoking lapse, this is rarely the case. Rather,
79%–97% of individuals who experience a smoking lapse subsequently
return to some pattern of regular smoking (e.g., indicated
by 3 or more consecutive days of smoking; Baer et al., 1989;
Brandon et al., 1990; Garvey et al., 1992; Kenford et al., 1994;
Shiffman et al., 1996). The apparent inevitability of a smoking
lapse leading to full relapse is of great concern because initial
smoking lapses are common and cannot always be avoided, and
the mechanisms underlying the lapse–relapse association have not
been elucidated.
A number of explanations in the addictions research literature
point to a direct and causal role of lapse in increasing relapse
probability. It has been suggested that negative cognitive and
affective reactions to a lapse, referred to as abstinence violation
effects (AVEs; e.g., feelings of defeat, guilt), undermine quitting
success by promoting further drug taking (Marlatt & Gordon,
1985). At present, studies relating AVE reactions to relapse have
reported mixed findings (Shiffman et al., 1996).
Reexposure to the pharmacological effects of the drug during
the lapse is also believed to directly promote relapse. A rich body
of preclinical research has demonstrated that after operant responding
for drugs has been acquired and subsequently extinguished,
a single injection of a drug, but not saline, will reinstate
drug-seeking behavior (de Wit, 1996; Shaham, Shalev, Lu, de Wit,
& Stewart, 2003). Such reinstatement, or priming effects, have
been shown to occur in animals across a wide variety of drugs,
including nicotine (Chiamulera, Borgo, Falchetto, Valerio, & Tessari,
1996; Shaham, Adamson, Grocki, & Corrigall, 1997).
There is also a growing appreciation of the importance of
nonpharmacological factors and associative mechanisms in drug
self-administration and relapse dynamics (Bouton, 2002; Caggiula
et al., 2001). Drug-associated stimuli have also been shown to
reinstate drug-seeking behavior in animals when presented after
extinction in the absence of the drug (reviewed in Shaham et al.,
2003). For example, a recent study demonstrated that contingent
presentation of stimuli previously associated with nicotine was
sufficient to reinstate nicotine-seeking behavior in rats (Paterson,
Froestl, & Markou, 2005). Furthermore, stimulus effects may be
critically important for nicotine reinforced behavior. Stimuli associated
with nicotine delivery have been shown to potentiate acquisition,
retard extinction, and facilitate the reacquisition of nicotine
self-administration in rodent models of nicotine selfadministration
(Caggiula et al., 2001, 2002; Donny et al., 1998).
These data suggest that the drug-associated cues present during a
lapse may also play an important and direct role in increasing the
motivation to use drugs.
At this time, variations of the drug reinstatement model have
been used to a limited extent with humans. Doses of alcohol,
Laura M. Juliano, Department of Psychology, American University;
Eric C. Donny, Elisabeth J. Houtsmuller, and Maxine L. Stitzer, Behavioral
Pharmacology Research Unit, Johns Hopkins University School of
Medicine.
Eric C. Donny is now at the Department of Psychology, University of
Pittsburgh.
This work was supported by National Institute on Drug Abuse Grant
R01 DA013125-02, National Cancer Institute Grant R01 CA99241, and
National Institute on Drug Abuse postdoctoral training Grant DA07209.
We thank Kristen McCausland and Kimberly Mudd for assisting with data
collection. We also thank Paul Nuzzo, Linda Felch, Ken Kolodner, and Rui
Li for assisting with statistical analyses. The National Institute on Drug
Abuse provided the experimental cigarettes.
Correspondence concerning this article should be addressed to Laura M.
Juliano, Department of Psychology, American University, 4400 Massachusetts
Avenue, NW, Washington, DC 20016. E-mail: [email protected]
Journal of Abnormal Psychology Copyright 2006 by the American Psychological Association
2006, Vol. 115, No. 1, 166–173 0021-843X/06/$12.00 DOI: 10.1037/0021-843X.115.1.166
166
cocaine, or heroin have been shown to increase drug craving in
users of the particular drug after a short period of abstinence (de
Wit, 1996). Studies have also shown that priming doses of alcohol
increase alcohol self-administration in alcoholics (Bigelow, Griffiths,
& Liebson, 1977; Ludwig & Wikler, 1974) and social drinkers
(de Wit & Chutuape, 1993). Cocaine users are also more likely
to choose cocaine over money after a priming dose of cocaine
(Donny, Bigelow, & Walsh, 2004).
Only one published study to date has directly and prospectively
examined the effects of smoking reexposure after a brief abstinence
period in humans (Chornock, Stitzer, Gross, & Leischow,
1992). In this study, after 3 days of required smoking abstinence,
participants were randomly assigned to either smoke five of their
own cigarettes or remain abstinent during a discrete time period.
Afterward, all participants were free to return to smoking during a
4-day observation period. Participants who experienced the programmed
lapse returned to smoking more rapidly than those who
did not. This study provides important empirical evidence that
smoking exposure after abstinence increases the probability of
subsequent smoking. However, this study cannot help to discern
whether smoking exposure led to subsequent smoking because of
exposure to nicotine in the cigarette smoke or to the other familiar
stimulus properties of smoking.
Nicotine is believed to be the main pharmacologically active
ingredient in cigarette smoke responsible for maintaining smoking
behavior (Stolerman & Jarvis, 1995). However, it has been hypothesized
that nonnicotine smoking-associated stimuli may also
play a crucial role in smoking maintenance and relapse, presumably
because of learned associations with nicotine (Caggiula et al.,
2001; Rose, Behm, Westman, & Johnson, 2000). Previous research
has demonstrated that both nicotine and denicotinized cigarettes
are capable of alleviating craving and withdrawal symptoms
(Gross, Lee, & Stitzer, 1997; Juliano & Brandon, 2002; Pickworth,
Fant, Nelson, Rohrer, & Henningfield, 1999), and that denicotinized
cigarettes function as a reinforcer (Shahan, Bickel, Madden,
& Badger, 1999). However, no published study to date has evaluated
the impact of cigarettes with varying nicotine contents on
lapse exposure effects.
The goal of the current study was to evaluate the effects of a
smoking-lapse episode on relapse outcomes and to determine the
importance of nicotine in smoking-lapse exposure effects. Smokers
who were not seeking cessation treatment participated in a
10-day study that involved a temporary quit attempt during which
a smoking-lapse episode was experimentally manipulated. Monetary
incentives were used to introduce uniform levels of pre- and
postmanipulation abstinence motivation. We compared the effects
of smoking nicotine-containing cigarettes, smoking denicotinized
cigarettes, or not lapsing on subsequent smoking likelihood. It was
hypothesized that individuals in the two smoking-lapse conditions
(i.e., exposed to nicotine or denicotinized cigarettes) would have
shorter latency to self-initiated smoking than those in the no-lapse
condition. Predictions concerning the comparison of nicotine and
denicotinized cigarettes were less straightforward. On one hand, it
is possible that smoke containing nicotine would more effectively
activate brain reward systems (Balfour, Wright, Benwell, & Birrell,
2000; Di Chiara, 2000) or more closely approximate smoking
conditioning histories and thus be more likely to reinstate subsequent
drug taking. On the other hand, the similarity of subjective
and reinforcing effects between nicotine and denicotinized cigarettes
in previous studies suggests that exposure to smoking stimuli
in the absence of nicotine may be sufficient to motivate subsequent
drug taking via conditioning or other mechanisms, effectively
overshadowing any effect of nicotine.
Method
Participants
Cigarette smokers (N 87) were recruited from the community through
newspaper advertisements and flyers. During a screening telephone call,
potential volunteers were told that this was not a stop-smoking program but
that the research would involve a “practice quit attempt.” They were
informed that they would be asked to stop smoking for several days but that
they may also be asked to smoke several cigarettes as part of the study
following a few days of abstinence. Those who indicated they wished to
make a permanent quit attempt within the next 30 days were screened out
of the sample at this point. Other inclusion criteria were as follows: 18–65
years of age, history of smoking at least 10 cigarettes per day for the past
year, negative pregnancy and illicit drug screen tests, and medically
healthy. A subset of participants (n 60; 69%) achieved the required 4
days of continuous abstinence and were randomly assigned to the experimental
manipulations. The characteristics of participants who did and did
not achieve the initial 4 days of continuous abstinence are described in
Table 1.
Materials
The experimental cigarettes were developed by Ultratech (Lafayette
Hills, Pennsylvania). The denicotinized cigarettes contained a subpharmacological
dose of nicotine (0.07 mg), and the nicotine cigarettes contained
0.6 mg nicotine. The two cigarettes had equivalent tar levels (11 mg). To
maintain double-blind experimental conditions, experimenters who had no
contact with the participants set out cigarettes ahead of time.
Table 1
Participant Characteristics
Characteristic
Randomly assigned
(n 60)
Dischargeda
(n 27)
Gender
% Women 48 52
% Men 52 48
Race (%)
Caucasian 55 41
African American 40 48
Asian 5 4
Other 0 7
Age (years) 37.25 (13.97) 40.15 (13.14)
Cigarettes per day 20.29 (9.83) 20.13 (9.75)
Years smoked 17.99 (13.42) 22.02 (13.08)
FTND (0–10) 5.12 (2.10) 5.81 (2.18)
CO at baseline (ppm) 17.65 (10.50) 18.93 (11.86)
Contemplation Ladder (0–10) 7.67 (2.63) 7.88 (2.47)
Beck Depression Inventory (0–63) 9.61 (8.73) 6.42 (7.63)
Previous serious quit attempts 3.39 (5.01) 3.74 (6.19)
Abstinence confidence (0–6) 5.05 (1.66) 5.15 (1.69)
Desire to quit (0–6) 5.50 (1.73) 5.92 (1.26)
Note. Values are means and standard deviations (in parentheses) unless
otherwise noted. FTND Fagerstro¨m Test for Nicotine Dependence;
CO carbon monoxide.
a Participants were discharged from the study if they smoked during the
first 4 days of required abstinence.
SMOKING LAPSE EXPOSURE EFFECTS 167
Procedure
Participants who passed the brief phone screening attended a baseline
visit to determine final eligibility (i.e., medical, drug, and pregnancy
screen), complete baseline assessments, and receive study instructions.
Participants were told that their practice quit attempt would last 10 days
and that they must remain completely abstinent for the first 4 days (compensated
$80.00 for doing so) to continue participation in the study. They
were told that the purpose of the study was to examine responses to
smoking after a brief period of abstinence and that there was a two out of
three chance that they would be asked to smoke cigarettes (that could
contain either nicotine or no nicotine) on the 4th day of the abstinence
period.
Participants chose a quit day, which always occurred on a Sunday
(usually within 1 week of the baseline screening visit) and were instructed
to quit smoking at 4:30 p.m. Participants visited the laboratory the following
day (Monday—Day 1) and were given a brief (about 45 min) individual
smoking cessation counseling session that included information about how
to anticipate and prepare for high-risk situations and tips for dealing with
nicotine withdrawal symptoms. All participants were also given a smoking
cessation booklet that was developed by our laboratory on the basis of
empirically validated principles of effective smoking cessation. The purpose
of these interventions was to help as many participants as possible
achieve the required 4 days of smoking abstinence necessary to participate
in the experimental phase of the study. Participants returned to the laboratory
on Tuesday (Day 2), Wednesday (Day 3), and Thursday (Day 4) to
complete measures, submit smoking self-monitoring forms, sign a statement
that they have not smoked, and provide breath carbon monoxide (CO)
and salivary cotinine samples to validate self-reported smoking abstinence.
Participants who reported smoking or had a carbon monoxide reading
greater than six parts per million or a salivary cotinine reading greater than
1 on a NicAlert (Nymox Pharmaceutical, Maywood, New Jersey) strip
(30 ng/l) during Visits 2–4 were discharged from the study and paid
$5.00 for each of their visits to the laboratory. The cotinine criterion was
not applied to Day 1 because there may have been residual elevations from
prior smoking. Participants who demonstrated continuous abstinence at the
morning Day 4 visit were randomly assigned to one of three experimental
manipulations: (a) smoke five nicotine-containing cigarettes, (b) smoke
five denicotinized cigarettes, or (c) no lapse. For participants assigned to
the smoking conditions, the first cigarette was smoked in the laboratory
through a puff topography device (data not reported). Heart rate and time
spent smoking the cigarette were recorded. Afterward, participants provided
a carbon monoxide sample and completed the cigarette rating questionnaire
as well as measures of craving, mood, withdrawal, confidence,
and desire to quit. Participants in the smoking conditions were then
provided with four additional cigarettes of the same type to smoke in their
natural environment over the next 4 hr. They were instructed to smoke the
four experimental cigarettes on an ad libitum basis and to refrain from
smoking any other cigarettes. Participants in the no-lapse condition were
instructed to continue to abstain. When participants returned to the laboratory
later that afternoon, they submitted four cigarette butts (smoking
conditions only), provided salivary cotinine and expired air carbon monoxide
samples, and completed measures described below. All participants
reported having complied with the instructions, and carbon monoxide
readings were consistent with self-reports.
At that time, all participants were instructed to abstain from smoking for
the next 6 days and were reminded that they could receive abstinence
incentives if they did so. The abstinence incentive schedule was modeled
after a procedure developed by Donny et al. (2004) and used a series of
daily choices between smoking versus money. The series began with
$12.00 per day payment for confirmed smoking abstinence on Days 5 and
6. The pay amount then decreased to $9.00 per day for Days 7 and 8, and
to $6.00 per day for Days 9 and 10. As the payment for abstinence
declined, it was anticipated that participants would be more inclined to
smoke. Participants were informed that the chance to earn abstinencecontingent
payments would stop as soon as smoking was detected. To
ensure that follow-up requirements were not a factor in the decision to
smoke or remain abstinent, we told participants that if they smoked, they
would still be required to attend all remaining laboratory visits at a pay rate
of $5.00 per visit. Although relapse was defined as detection of the first
smoking episode after the final Day 4 visit, the first instance of smoking
generally marked a return to daily smoking. For example, among 18
participants who initiated smoking within 72 hr of the manipulation, 17
continued to smoke on at least the next 3 consecutive days.
Participants returned to the laboratory on Days 5, 6, 8, and 10 to
complete measures, submit self-monitoring forms, sign a statement that
they had or had not smoked, and provide breath carbon monoxide and
salivary cotinine samples. Smoking was implicated by a breath carbon
monoxide greater than 6 ppm, saliva cotinine dipstick reading greater than
1 (i.e., 30 ng/l), or self-report of any smoking. A maximum of $184.00
could be earned for study participation: $5.00 for each of 10 laboratory
visits, $80.00 for the first 4 days of continuous abstinence, and $54.00 for
postmanipulation abstinence.
Measures
Breath carbon monoxide. Breath carbon monoxide samples were collected
(Vitalograph, Lenexa, Kansas) to verify smoking status at every
study visit. Pre- to postsmoking changes in carbon monoxide level also
provided a measure of the amount of smoke inhaled during the experimental
manipulation.
Salivary cotinine. We assessed cotinine during each of the laboratory
visits using the NicAlert Strip Test Kit (Nymox Pharmaceutical, Maywood,
New Jersey). Test strips provide a reading between 0 and 6 that indicates
the level of recent smoking exposure. Test strip readings have been shown
to reliably differentiate smokers and nonsmokers and correlate with gas
chromatography cotinine analysis. Smoking abstinence was indicated by a
reading of 0 (1–10 ng/l cotinine concentration) or 1 (10–30 ng/l
cotinine concentration). Additional saliva samples were collected under the
guise that they would be sent out for a more sensitive analysis of whether
the participant smoked. This type of bogus pipeline procedure has been
shown to increase the accuracy of self-reported smoking behavior (Aguinis,
Pierce, & Quigley, 1993).
The following three self-report measures were administered at baseline
only:
Smoking history questionnaire. This questionnaire contained questions
about smoking history and included a standardized measure of nicotine
dependence, the Fagerstro¨m Test for Nicotine Dependence (Heatherton,
Kozlowski, Frecker, & Fagerstro¨m, 1991).
Beck Depression Inventory. The Beck Depression Inventory (Beck,
Steer, & Brown, 1996) is a well-validated measure of depression severity
that measures the intensity of 21 depressive symptoms on a 4-point scale
ranging from 0 to 3, with higher scores reflecting progressively more
severe symptomatology.
Contemplation Ladder. The Contemplation Ladder assesses readiness
to quit smoking by having respondents circle a number between 0 (no
thoughts of quitting) and 10 (taking action to quit). It has been shown to
predict subsequent participation in smoking cessation programs (Biener &
Abrams, 1991) and quitting success (Abrams, Herzog, Emmons, & Linnan,
2000).
An additional battery of self-report measures described below was
administered at baseline, during each study visit, and before and after the
experimental manipulation.
Confidence/desire to quit. This measure was developed for this
study. Participants were asked how confident they were that they could
“quit smoking at this time,” “abstain from cigarettes for the next 24
hours,” “abstain from cigarettes until the end of the study,” and that
they would “not be smoking one month from today.” Confidence was
168 JULIANO, DONNY, HOUTSMULLER, AND STITZER
rated on a 7-point scale ranging from 0 (not at all confident) to 6
(extremely confident). The four items demonstrated very high internal
consistency ( .90) and were averaged to form a single confidence
score. Participants were also asked to rate their “desire to quit smoking
at this time” on a 7-point scale ranging from 0 (no desire at all) to 6
(extreme desire).
Positive and Negative Affect Schedule. The Positive and Negative
Affect Schedule (Watson, Clark, & Tellegen, 1988) is a reliable ( .85)
and valid measure of positive and negative affect. It lists 20 adjectives that
participants rate on a 5-point Likert scale ranging from 1 (not at all) to 5
(extremely) indicating how they feel “at this moment.” Ten adjectives
assess positive affect, and 10 adjectives assess negative affect. Total scores
for positive affect and negative affect were used in the analysis, as well as
the single item “guilt.”
Craving scale. This scale consisted of five items that assessed craving
to smoke. Items were as follows: “How pleasant would a cigarette be right
now?,” “How much of an urge or desire do you have to smoke right now,
just for the pleasure of smoking?,” “How much do you need to smoke right
now, just for relief?,” “How much do you want to smoke right now?,” and
“How much do you crave a cigarette right now?” Items were presented on
a 100-mm visual analogue scale anchored on the left with not at all and on
the right with an awful lot. The first four items of this scale have been
shown to be sensitive to smoking abstinence under controlled conditions
(Schuh & Stitzer, 1995). The fifth item was added to the scale in the current
study to improve reliability. The five items demonstrated very high internal
consistency (mean .95) and were averaged to form a total craving
score.
Nicotine withdrawal. Participants rated nicotine withdrawal symptoms
on a 4-point scale ranging from 0 (none) to 3 (severe). A total withdrawal
score (Hughes, 1992) was calculated by summing ratings for the following
six Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American
Psychiatric Association, 1994) items: depression, irritability, anxiety,
difficulty concentrating, restlessness, and increased appetite. The six items
demonstrated high internal consistency (mean .85).
Finally, a cigarette ratings questionnaire was administered one time to
assess responses to the initial test cigarette during lapse exposure. Ratings
were made on a 100-mm visual analogue scale anchored on the left with
not at all and on the right with extremely. The items were as follows:
pleasant, tasted good, harsh, strong, tasted different than my usual brand,
enjoyable sensations on lips, enjoyable sensations on throat, smelled good,
reduced craving, reduced irritability, dizzy, relaxing, buzzed, nauseous,
liked, and stimulating.
Statistical Analytic Strategy
Analysis of variance (ANOVA) was used to compare reactions to
nicotine-containing and denicotinized cigarettes after smoking the first
lapse cigarette and after all five lapse cigarettes. ANOVA was also used to
make postmanipulation comparisons among all three conditions, which
were followed up with simple comparison t tests. Smoking behavior was
tracked for 6 days after the experimental manipulation, and thus the
maximum time abstinent was 144 hr, at which point data were censored.
We analyzed progressions to self-initiated smoking using Cox regression
with the number of hours from the end of the final Day 4 visit to the first
instance of self-initiated smoking as the unit of time. We compared
abstinence survival rates between the nicotine and denicotinized conditions
and between each of the smoking conditions and the no-lapse condition.
Because of strong a priori predictions about the direction of the findings,
a one-tailed alpha of .05 was used as the significance criterion when the
nicotine or denicotinized group was compared with the no-lapse group. A
two-tailed alpha of .05 was used as the significance criterion for all other
comparisons.
Results
Baseline Data
A series of ANOVAs revealed no differences among the three
groups at baseline on expired air carbon monoxide, age, smoking
rate, number of years smoked, nicotine dependence, cravings,
withdrawal, abstinence confidence, desire to quit, and depression.
There were also no significant differences on the above variables
between participants who achieved the initial 4 days of required
abstinence and those who did not (see Table 1). There were also no
differences between groups on any measures during each of the
first 4 days of required abstinence.
Manipulation Check Data
As can be seen in Table 2, a number of indicators of smoking
exposure suggest that the two types of experimental cigarettes
were smoked similarly. For the first lapse cigarette, there were no
significant differences between the nicotine and denicotinized conditions
in total smoking time, carbon monoxide boost, or cigarette
butt weights. The first lapse cigarette produced significantly
greater heart rate boost in the nicotine condition relative to the
denicotinized condition, confirming that a pharmacological active
dose of nicotine was ingested only in the nicotine condition.
Verbal reports and objective measures (carbon monoxide and
cigarette butt weights) indicated that participants in the nicotine
and denicotinized conditions equally complied with instructions to
smoke four additional cigarettes in their natural environments. At
the end of the manipulation, both conditions produced significantly
greater carbon monoxide boost than the no-lapse condition.
Subjective Reactions to the Lapse Manipulation
Subjective reactions to the lapse manipulation are summarized
in Table 2. On the cigarette ratings questionnaire, there was a trend
for nicotine cigarettes to produce greater reports of dizziness than
the denicotinized cigarettes. Denicotinized cigarettes produced
significantly greater ratings on “harsh” and “tastes different than
usual brand” items. There were no other differences between the
two types of cigarettes on the remaining cigarette rating scale
items. There was a trend for the first lapse nicotine cigarette to
produce greater craving reduction from premanipulation levels
than the denicotinized cigarette. However, there was no difference
in craving reduction between the cigarette types after all five lapse
cigarettes were smoked, with the nicotine and denicotinized cigarettes
producing nearly equivalent reductions in craving. Participants
in both the nicotine and denicotinized smoking conditions
experienced significantly greater craving reduction after smoking
the first lapse cigarette and after smoking all five lapse cigarettes
compared with participants in the no-lapse condition. There were
no differences between the nicotine and denicotinized condition in
withdrawal ratings after the first lapse cigarette or after all five
cigarettes. After the manipulation, participants in both the nicotine
and denicotinized conditions had significantly lower ratings of
nicotine withdrawal than those in the no-lapse condition.
There were no differences among the conditions in postmanipulation
ratings or pre- to postmanipulation changes in positive or
negative affect, guilt, abstinence confidence, or desire to quit.
SMOKING LAPSE EXPOSURE EFFECTS 169
Latency to Smoke
As shown in Figure 1, the percentage of participants abstinent at
the end of the 6-day follow-up period was 70% for the no-lapse
group, relative to 45% and 40% among those who smoked
nicotine-containing and denicotinized cigarettes, respectively. As
is shown in Figure 1, when compared with the no-lapse condition,
the denicotinized condition produced a significantly more rapid
return to smoking (Wald 4.09, p .022, hazard ratio [HR]
2.755, 95% confidence interval [CI] 1.031–7.358), whereas the
nicotine condition revealed a strong trend (Wald 2.08, p .075,
HR 2.081, 95% CI 0.769 –5.634). The effects appear to be
substantial as individuals in both the denicotinized and nicotine
conditions were more than twice as likely to smoke during the
6-day follow-up period compared with those in the no-lapse con-
Table 2
Reactions to the Experimental Manipulation
Variable Nicotine Denicotinized No lapse Significance
CO boost after first cigarette (ppm) 4.45 (2.31) 4.05 (2.67) — (2, 37) ns
CO boost after experimental manipulation (ppm) 9.15 (6.67)a 7.20 (4.66)a 0.40 (1.35)b F(2, 37) 22.42, p .001
Smoking time (s) 408.65 (96.77) 363.65 (93.31) — ns
Cigarette butt weights
First cigarette 0.42 (0.11) 0.44 (0.14) — ns
Four cigarettes 1.75 (0.48) 1.59 (0.80) — ns
Heart rate boost (beats per minute) 9.05 (6.09) 1.01 (5.86) — F(1, 38) 12.68, p .001
Dizzy (0–100) 54.26 (37.27) 33.95 (31.44) — F(1, 38) 3.40, p .073
Harsh (0–100) 32.47 (35.80) 59.10 (36.38) — F(1, 38) 5.30, p .027
Tastes different than usual brand (0–100) 68.16 (38.71) 89.05 (21.46) — F(1, 38) 4.40, p .043
Craving change
After first cigarette 24.22 (32.77) 8.20 (26.89) — F(1, 38) 2.77, p .105
After all five cigarettes 15.09 (13.28)a 15.20 (21.93)a .14 (11.23)b F(2, 53) 5.08, p .010
Withdrawal ratings
After first cigarette 3.55 (3.38) 3.44 (3.11) — ns
After all five cigarettes 3.40 (3.03)a 3.65 (2.91)a 6.70 (4.82)b F(2, 59) 4.95, p .010
Note. Values are means and standard deviations (in parentheses). A dash indicates that there was no measurement of the variable. Significant overall analyses
of variance among the three conditions were followed up with simple comparison t tests; dissimilar subscript letters indicate a significant difference between groups
at p .05 (two-tailed). There were no significant differences between the nicotine and denicotinized cigarettes on the following visual analogue scale items:
pleasant, tasted good, strong, enjoyable sensations on lips, enjoyable sensations on throat, smelled good, reduced craving, reduced irritability, relaxing, buzzed,
nauseous, liked, and stimulating. There were no significant postmanipulation differences among the three conditions in positive affect, negative affect, desire to
quit, or confidence.
CO carbon monoxide.
Figure 1. Survival curves showing time (hours) to self-initiated smoking for the three experimental conditions.
170 JULIANO, DONNY, HOUTSMULLER, AND STITZER
dition. Cox regression analysis comparing the nicotine and denicotinized
conditions revealed no significant difference in survival
distributions (Wald 0.450, p .502, HR 0.756, CI
0.333–1.714), suggesting that the nicotine content of the cigarettes
had no impact on survival probabilities.
Discussion
Using a short-term prospective model of smoking cessation and
relapse, we attempted in this study to disentangle critical components
of a smoking-lapse episode to better understand lapse mechanisms
that drive the motivation for subsequent smoking. To this
end, we compared the effects of lapsing with nicotine-containing
cigarettes, lapsing with denicotinized cigarettes, or not lapsing on
subsequent smoking likelihood. Smoking outcomes did not significantly
differ between the nicotine and denicotinized conditions
(see Figure 1). Relative to the no-lapse condition, exposure to
either of the cigarette types more than doubled the probability of
subsequent smoking during the 6-day follow-up, with the denicotinized
condition producing a significantly different relapse curve,
and the nicotine condition revealing a strong trend (see Figure 1).
The current findings are consistent with an earlier study that
demonstrated that an experimentally induced smoking lapse with
one’s own brand of cigarettes after 3 days of abstinence promoted
a subsequent return to smoking (Chornock et al., 1992). The data
are also consistent with prospective clinical studies showing an
association between lapse and relapse (Shiffman et al., 1996) and
with drug reinstatement effects that have been widely demonstrated
with animal models (Shaham et al., 2003). The first instance
of smoking after abstinence appears to play a direct and
potentially causal role in the relapse process and has significant
detrimental effects on quitting success. However, the lack of
difference between the nicotine-containing and denicotinized cigarettes
suggests that the acute delivery of nicotine in cigarette
smoke may not be a necessary causal factor underlying the lapse to
relapse process but rather that other factors such as conditioning
and/or expectancies may also play a critical role.
The lack of difference in smoking outcomes between the nicotine
and denicotinized conditions may not be that surprising considering
that the two cigarette types produced similar effects across
various subjective outcomes, including reductions in craving and
withdrawal. Previous studies have also reported that nicotine and
denicotinized cigarettes produce similar reductions in craving and
withdrawal, presumably because of conditioned effects (e.g., Butschky,
Bailey, Henningfield, & Pickworth, 1995; Dallery, Houtsmuller,
Pickworth, & Stitzer, 2003; Pickworth et al., 1999).
There are a number of possible conceptualizations that could
account for the ability of cigarette smoke without nicotine to
promote subsequent smoking. First, the stimulus components of
denicotinized cigarette smoke or the act of smoking (e.g., puffing,
inhaling) may produce conditioned responses because of previously
learned associations with nicotine. Regardless of different
conceptualizations about the nature of such conditioned reactions
(e.g., compensatory, appetitive), they are believed to increase
drug-taking motivation. It is also possible that the nonnicotine
components of cigarette smoke have direct rewarding effects and
that the exposure to such components motivated subsequent smoking.
The findings from this study may or may not generalize to a
scenario in which a smoker smokes only denicotinized cigarettes
prior to quitting (undergoing extinction) and then lapses with a
denicotinized cigarette. Future research on reactions to denicotinized
cigarettes both in the context of acute administration and
extended administration (i.e., sufficient time for possible extinction
to occur) may shed light on the mechanisms by which they
influence smoking motivation.
It is also possible that the denicotinized cigarettes may have
produced frustration because of lack of reward and thus motivated
smoking; however, there were no detectable differences across the
groups in positive or negative affect. There were also no group
differences in guilt, abstinence confidence, or desire to quit. These
results may not be surprising given that the lapse was dictated by
the experimental protocol and not self-initiated. Negative cognitive
and emotional reactions to a lapse (i.e., AVEs) are more likely to
have an influence during self-initiated smoking lapses in the natural
environment. However, it is notable that, unlike the current
study, Chornock et al. (1992) found increased guilt among participants
who were assigned to lapse. The inconsistent findings across
studies may be due to differences between the studies such as the
type of lapse cigarettes (experimental cigarettes vs. own brand) or
the incentives provided for abstinence (monetary vs. verbal
encouragement).
Latency to self-initiated smoking across the 6-day follow-up
period varied from 30 min to 118 hr. For some individuals, the first
point of self-initiated smoking occurred as late as Day 5 of the
6-day follow-up period, and thus we were unable to evaluate time
to relapse, which would have required a more extended period of
observation. Among participants who were classified as relapsed,
abstinent days rarely occurred after the first point of self-initiated
smoking, and thus the classification appeared valid for these participants.
Nevertheless, the limited length of follow-up after the
lapse limits to some extent the conclusions that can be drawn about
the lapse to relapse process.
The volunteers in this study were not trying to quit smoking
permanently, and this characteristic of participants may limit the
generality of findings. All participants in the study were aware that
the maximum time of abstinence was 10 days and thus may have
had different cognitive and/or affective reactions to the experimental
manipulation than individuals embarking on a permanent abstinence
attempt. Participants who were actively seeking smoking
treatment and/or who were planning to quit smoking in the next 30
days were excluded so as not to jeopardize their cessation efforts
with a lapse, which we felt would have created an ethical conflict.
Rather, monetary incentives were used to increase participants’
motivation for abstinence both before and after the experimental
manipulation. The abstinence incentives used in the current study
were successful in delaying return to smoking relative to Chornock
et al.’s (1992) study. In that study, no monetary incentives were
used and participants were simply encouraged to remain abstinent
after the experimental manipulation. Under those conditions, more
than 70% of the participants smoked within 5 hr of the experimental
manipulation, and only 9% were abstinent at the end of the
4-day follow-up period. In the current study, only 12% of participants
smoked within the first 5 hr of the manipulation, and more
than 50% were still abstinent at the end of the 6-day follow-up
period. Thus, the use of monetary incentives appears to have
increased the sensitivity of the model for detecting experimentally
induced lapse exposure effects by prolonging the average latency
to relapse (i.e., preventing floor effects). This model, which uses
SMOKING LAPSE EXPOSURE EFFECTS 171
monetary incentives to motivate abstinence, may prove useful for
examining effects of medications and behavioral interventions or
for identifying individual differences in relapse propensity. Furthermore,
replication of the findings with a sample of smokers with
intrinsic motivation to quit would be desirable because this would
help to validate the use of what appears to be a sensitive and useful
short-term model of cessation and relapse.
Another potential limitation to the generality of findings is that
experimental cigarettes were used and lapse effects may differ in
the context of smoking one’s usual brand of cigarette. Compared
with the nicotine cigarettes, the denicotinized cigarettes produced
greater ratings of harsh and tastes different than usual brand. Such
taste differences could be a function of the absence of nicotine or
other distinctive qualities of the denicotinized cigarettes resulting
from the process used to eliminate the nicotine. However, participants
had no prior exposure to either of the experimental cigarettes
used in this study, and both were rated as tasting different
than their usual brand. It would be interesting to evaluate the
effects of lapsing with one’s own brand of cigarettes in the context
of the current experimental model. We would predict that own
brand cigarettes, by virtue of their more potent conditioning effects,
would produce even stronger lapse exposure effects than
those observed with nicotine-containing cigarettes in the current
study.
Participants had to initially demonstrate 4 days of continuous
smoking abstinence to be eligible to participate in the study. This
may have created a selection bias in that only those who were
capable of abstaining for 4 days were exposed to the experimental
manipulation. However, it is encouraging that there were no differences
in baseline characteristics between individuals who did
and did not achieve abstinence during the first 4 days of the study
(see Table 1), suggesting that the participants exposed to the
manipulation were not substantively different from the larger body
of potential research participants. Furthermore, the elimination of
smokers who find it difficult to quit in the first place should result
in a relatively conservative assessment of lapse exposure phenomenon
(i.e., those eliminated may be even more sensitive to lapse
exposure effects).
Part of the experimental manipulation (i.e., smoking four additional
cigarettes or remaining abstinent) was not under direct
observation of the researchers, nor was smoking behavior during
the follow-up period. These design strategies provided a more
naturalistic experience for participants and thus increased external
validity of the study. However, they limit internal validity to some
extent by increasing reliance on self-report data. This is countered
to a large extent by the corroboration of self-report with objective
measures of smoking abstinence (e.g., carbon monoxide).
Finally, although the effects observed were convincing in magnitude
(see Figure 1), the study had limited power to detect
statistical differences because of the small sample size. The difference
between the nicotine and no-lapse group would have likely
reached traditional levels of significance with a larger sample size.
A power analysis indicated that we would have achieved statistical
significance ( p .05, one-tailed) with a sample size of 25 per
group given the event rate of 48.3% and HR (effect size) of 2.08.
Additional research is needed to extend the generality of findings
reported here. The lapse in this study was scheduled after 4
continuous days of abstinence, because the lapse rate has been
shown to be highest in early abstinence (e.g., Shiffman et al.,
1997), and early lapse (i.e., within 1–2 weeks of quitting) has been
shown to be a strong predictor of relapse (Kenford et al., 1994;
Smith et al., 2001). Nevertheless, under naturalistic conditions, the
time to first lapse varies widely across individuals. Future research
should evaluate lapse exposure effects after other more prolonged
periods of abstinence. In the current study, participants smoked
five cigarettes as part of the lapse exposure manipulation. Five
cigarettes were chosen to increase the salience of the manipulation.
However, it would be interesting in future studies to evaluate the
effects of a range of smoking reexposure doses to simulate the
variability in smoking-lapse doses encountered in the natural environment.
In light of the extensive animal literature showing
reinstatement of drug-seeking behavior after exposure to stress
(Shaham, Erb, & Stewart, 2000) or drug-associated environmental
cues (Shaham et al., 2003), it would be of interest to examine the
effects on smoking relapse of exposure to these other provocative
stimuli.
In summary, this study demonstrated under controlled conditions
that smoking lapse has a direct detrimental effect on subsequent
abstinence outcomes. The nicotine in cigarette smoke did not
appear to play a vital immediate role in the lapse to relapse
process. Future studies should continue to evaluate the mechanisms
by which cigarette smoke exposure, both with and without
nicotine, promotes subsequent smoking relapse. The data especially
suggest a need for further examination of nonnicotine components
of smoking in lapse to relapse mechanisms. After these
mechanisms are better understood, they may aid in development of
treatments that can prevent the progression from first lapse to
relapse.
References
Abrams, D. B., Herzog, T. A., Emmons, K. M., & Linnan, L. (2000).
Stages of change versus addiction: A replication and extension. Nicotine
& Tobacco Research, 2, 223–229.
Aguinis, H., Pierce, C. A., & Quigley, B. M. (1993). Conditions under
which a bogus pipeline procedure enhances the validity of self-reported
cigarette smoking: A meta-analytic review. Journal of Applied Social
Psychology, 23, 352–373.
American Psychiatric Association. (1994). Diagnostic and statistical manual
of mental disorders (4th ed.). Washington, DC: Author.
Baer, J. S., Kamarck, T., Lichtenstein, E., & Ransom, C. C., Jr. (1989).
Prediction of smoking relapse: Analyses of temptations and transgressions
after initial cessation. Journal of Consulting and Clinical Psychology,
57, 623–627.
Balfour, D. J., Wright, A. E., Benwell, M. E., & Birrell, C. E. (2000). The
putative role of extra-synaptic mesolimbic dopamine in the neurobiology
of nicotine dependence. Behavioural Brain Research, 113, 73–83.
Beck, A., Steer, R., & Brown, G. (1996). Beck Depression Inventory
manual. San Antonio, TX: Psychological Corporation.
Biener, L., & Abrams, D. B. (1991). The Contemplation Ladder: Validation
of a measure of readiness to consider smoking cessation. Health
Psychology, 10, 360–365.
Bigelow, G. E., Griffiths, R. R., & Liebson, I. A. (1977). Pharmacological
influences upon human ethanol self-administration. Advances in Experimental
Medicine and Biology, 85B, 523–538.
Bouton, M. E. (2002). Context, ambiguity, and unlearning: Sources of
relapse after behavioral extinction. Biological Psychiatry, 52, 976–986.
Brandon, T. H., Tiffany, S. T., Obremski, K. M., & Baker, T. B. (1990).
Postcessation cigarette use: The process of relapse. Addictive Behaviors,
15, 105–114.
Butschky, M. F., Bailey, D., Henningfield, J. E., & Pickworth, W. B.
172 JULIANO, DONNY, HOUTSMULLER, AND STITZER
(1995). Smoking without nicotine delivery decreases withdrawal in
12-hour abstinent smokers. Pharmacology Biochemistry and Behavior,
50, 91–96.
Caggiula, A. R., Donny, E. C., White, A. R., Chaudhri, N., Booth, S.,
Gharib, M. A., et al. (2001). Cue dependency of nicotine selfadministration
and smoking. Pharmacology Biochemistry and Behavior,
70, 515–530.
Caggiula, A. R., Donny, E. C., White, A. R., Chaudhri, N., Booth, S.,
Gharib, M. A., et al. (2002). Environmental stimuli promote the acquisition
of nicotine self-administration in rats. Psychopharmacology (Berlin),
163, 230–237.
Chiamulera, C., Borgo, C., Falchetto, S., Valerio, E., & Tessari, M. (1996).
Nicotine reinstatement of nicotine self-administration after long-term
extinction. Psychopharmacology (Berlin), 127, 102–107.
Chornock, W. M., Stitzer, M. L., Gross, J., & Leischow, S. (1992).
Experimental model of smoking re-exposure: Effects on relapse. Psychopharmacology
(Berlin), 108, 495–500.
Dallery, J., Houtsmuller, E. J., Pickworth, W. B., & Stitzer, M. L. (2003).
Effects of cigarette nicotine content and smoking pace on subsequent
craving and smoking. Psychopharmacology (Berlin), 165, 172–180.
de Wit, H. (1996). Priming effects with drugs and other reinforcers.
Experimental and Clinical Psychopharmacology (Berlin), 4, 5–10.
de Wit, H., & Chutuape, M. A. (1993). Increased ethanol choice in social
drinkers following ethanol preload. Behavioural Pharmacology, 4, 29–
36.
Di Chiara, G. (2000). Behavioral pharmacology and neurobiology of
nicotine reward and dependence. In F. Clementi, D. Formasari, & C.
Gotti (Eds.), Handbook of experimental psychology: Neuronal nicotinic
receptors (Vol. 144, pp. 603–750). Berlin, Germany: Springer-Verlag.
Donny, E. C., Bigelow, G. E., & Walsh, S. L. (2004). Assessing the
initiation of cocaine self-administration in humans during abstinence:
Effects of dose, alternative reinforcement, and priming. Psychopharmacology
(Berlin), 172, 316–323.
Donny, E. C., Caggiula, A. R., Mielke, M. M., Jacobs, K. S., Rose, C., &
Sved, A. F. (1998). Acquisition of nicotine self-administration in rats:
The effects of dose, feeding schedule, and drug contingency. Psychopharmacology
(Berlin), 136, 83–90.
Garvey, A. J., Bliss, R. E., Hitchcock, J. L., Heinold, J. W., & Rosner, B.
(1992). Predictors of smoking relapse among self-quitters: A report from
the Normative Aging Study. Addictive Behaviors, 17, 367–377.
Gross, J., Lee, J., & Stitzer, M. L. (1997). Nicotine-containing versus
de-nicotinized cigarettes: Effects on craving and withdrawal. Pharmacology
Biochemistry and Behavior, 57, 159–165.
Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerstro¨m, K. O.
(1991). The Fagerstro¨m Test for Nicotine Dependence: A revision of the
Fagerstro¨m Tolerance Questionnaire. British Journal of Addictions, 86,
1119–1127.
Hughes, J. R. (1992). Tobacco withdrawal in self-quitters. Journal of
Consulting and Clinical Psychology, 60, 689–697.
Juliano, L. M., & Brandon, T. H. (2002). Effects of nicotine dose, instructional
set, and outcome expectancies on the subjective effects of smoking
in the presence of a stressor. Journal of Abnormal Psychology, 111,
88–97.
Kenford, S. L., Fiore, M. C., Jorenby, D. E., Smith, S. S., Wetter, D., &
Baker, T. B. (1994). Predicting smoking cessation: Who will quit with
and without the nicotine patch. Journal of the American Medical Association,
271, 589–594.
Ludwig, A. M., & Wikler, A. (1974). “Craving” and relapse to drink.
Quarterly Journal of Studies on Alcohol, 35, 108–130.
Marlatt, G. A., & Gordon, J. R. (1985). Relapse prevention. New York:
Guilford Press.
Paterson, N. E., Froestl, W., & Markou, A. (2005). Repeated administration
of the GABA(B) receptor agonist CGP44532 decreased nicotine
self-administration, and acute administration decreased cue-induced reinstatement
of nicotine-seeking in rats. Neuropsychopharmacology, 30,
119–128.
Pickworth, W. B., Fant, R. V., Nelson, R. A., Rohrer, M. S., & Henningfield,
J. E. (1999). Pharmacodynamic effects of new de-nicotinized
cigarettes. Nicotine & Tobacco Research, 1, 357–364.
Rose, J. E., Behm, F. M., Westman, E. C., & Johnson, M. (2000).
Dissociating nicotine and nonnicotine components of cigarette smoking.
Pharmacology Biochemistry and Behavior, 67, 71–81.
Schuh, K. J., & Stitzer, M. L. (1995). Desire to smoke during spaced
smoking intervals. Psychopharmacology (Berlin), 120, 289–295.
Shaham, Y., Adamson, L. K., Grocki, S., & Corrigall, W. A. (1997).
Reinstatement and spontaneous recovery of nicotine seeking in rats.
Psychopharmacology (Berlin), 130, 396–403.
Shaham, Y., Erb, S., & Stewart, J. (2000). Stress-induced relapse to heroin
and cocaine seeking in rats: A review. Brain Research Reviews, 33,
13–33.
Shaham, Y., Shalev, U., Lu, L., de Wit, H., & Stewart, J. (2003). The
reinstatement model of drug relapse: History, methodology, and major
findings. Psychopharmacology (Berlin), 168, 3–20.
Shahan, T. A., Bickel, W. K., Madden, G. J., & Badger, G. J. (1999).
Comparing the reinforcing efficacy of nicotine containing and denicotinized
cigarettes: A behavioral economic analysis. Psychopharmacology
(Berlin), 147, 210–216.
Shiffman, S., Engberg, J. B., Paty, J. A., Perz, W. G., Gnys, M., Kassel,
J. D., et al. (1997). A day at a time: Predicting smoking lapse from daily
urge. Journal of Abnormal Psychology, 106, 104–116.
Shiffman, S., Hickcox, M., Paty, J. A., Gnys, M., Kassel, J. D., & Richards,
T. J. (1996). Progression from a smoking lapse to relapse: Prediction
from abstinence violation effects, nicotine dependence, and lapse characteristics.
Journal of Consulting and Clinical Psychology, 64, 993–
1002.
Smith, S. S., Jorenby, D. E., Fiore, M. C., Anderson, J. E., Mielke, M. M.,
Beach, K. E., et al. (2001). Strike while the iron is hot: Can stepped-care
treatments resurrect relapsing smokers? Journal of Consulting and Clinical
Psychology, 69, 429–439.
Stolerman, I. P., & Jarvis, M. J. (1995). The scientific case that nicotine is
addictive. Psychopharmacology (Berlin), 117, 2–10; discussion 14–20.
Watson, D., Clark, L. A., & Tellegen, A. (1988). Development and validation
of brief measures of positive and negative affect: The PANAS
scales. Journal of Personality and Social Psychology, 54, 1063–1070.
Received February 23, 2005
Revision received October 4, 2005
Accepted October 13, 2005
SMOKING LAPSE EXPOSURE EFFECTS 173