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Effects of Transdermal Nicotine During Imaginal Exposure to Anxiety andSmoking Cues in College Smokers

Sandra Baker Morissette and Tibor P. PalfaiBoston University

Suzy Bird GulliverVeterans Affairs Boston Health Care System, Boston University

School of Medicine, and Boston University

David A. Spiegel and David H. BarlowBoston University and Boston University School of Medicine

In a 2 (patch) 2 (smoking) 2 (anxiety) mixed design, 52 undergraduate smokers randomly received

a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants

imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking,

and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the

absorption/deprivation period, those who received the placebo reported significantly greater urge. During

the cue reactivity trials, a significant Patch Smoking Anxiety interaction effect was observed for

urge. However, participants who received nicotine still experienced moderate urges, indicating that

nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the

absorption/deprivation period or in response to the cues.

Transdermal nicotine is frequently prescribed to assist individ-

uals with smoking cessation. The rationale for nicotine replace-

ment therapies (NRTs), such as the nicotine patch, is that smokers

may slowly taper from nicotine, the primary addictive component

of smoking (Ashton & Golding, 1989; Balfour, 1990). Transder-

mal nicotine is marketed as a means of curbing subjective with-

drawal symptoms, including urge to smoke and anxiety. Urge to

smoke is commonly perceived as the most aversive part of tobacco

abstinence (e.g., Gritz, Carr, & Marcus, 1991; Shiffman & Jarvik,1976), making NRT appealing. Although NRT may aid physio-

logical and subjective withdrawal from nicotine, the extent to

which it reduces urges in response to everyday smoking cues is

unclear. For example, common triggers of smoking urge include

negative affect (Payne, Schare, Levis, & Colletti, 1991; Tiffany &

Drobes, 1990; Zinser, Baker, Sherman, & Cannon, 1992),

smoking-related thoughts, and environmental cues for smoking

(Drobes & Tiffany, 1997; Elash, Tiffany, & Vrana, 1995; Maude-

Griffin & Tiffany, 1996). Despite the common use of the nicotine

patch, little controlled research has investigated how transdermal

nicotine influences urge response to these salient triggers.In the current study, we explored how the nicotine patch af-

fected both smoking urge and anxiety responses during imaginal

exposure to smoking and anxiety cues. Although negative affect in

general has been documented to influence smoking, of particular

interest in the present study was the influence of anxiety cues and

responses, due to the common occurrence of anxiety during nico-

tine withdrawal and its role as a risk factor for relapse (Shiffman,

1982). Smokers often anecdotally indicate that they smoke in

response to feeling anxious. Data also indicate that anxiety influ-

ences smoking topography (i.e., increased puff volume; C. S.

Pomerleau & Pomerleau, 1987). Thus, anxiety not only is a com-

mon symptom of nicotine withdrawal, but it can also serve as a

salient trigger of smoking behavior. Knowledge of how nicotine

affects anxiety and smoking urges during high-risk trigger situa-tions, such as those involving anxiety and smoking cues, may help

specify the conditions under which NRT is or is not effective.

Several studies have investigated whether nicotine from ciga-

rettes, and not smoking per se, is anxiolytic (Gilbert, Robinson,

Chamberlin, & Spielberger, 1989; Hatch, Bierner, & Fisher, 1983;

Juliano & Brandon, 2002; Kassel & Unrod, 2000; O. F. Pomerleau,

Turk, & Fertig, 1984). However, to date, no studies have examined

the potential anxiolytic effects of nicotine when administered

transdermally. Because transdermal nicotine is administered con-

tinuously, and results in much slower absorption than tobacco

smoking, it may or may not affect anxiety in the same manner.

Sandra Baker Morissette, Center for Anxiety and Related Disorders,

Boston University. Tibor P. Palfai, Department of Psychology, Boston

University. Suzy Bird Gulliver, Psychology Service, Veterans Affairs

Boston Health Care System; Department of Psychiatry, Boston University

School of Medicine; and Department of Psychology, Boston University.

David Spiegel and David H. Barlow, Center for Anxiety and Related

Disorders, Boston University; Department of Psychology, Boston Univer-

sity; and Department of Psychiatry, Boston University School of Medicine.

Sandra Baker Morissette is now at the Psychology Service, Veterans

Affairs Boston Health Care System, and the Department of Psychiatry,

Boston University School of Medicine.

These data were originally presented at the annual meeting of the

Association for the Advancement of Behavior Therapy, Philadelphia,

Pennsylvania, November 2000. This research was supported by an Amer-

ican Psychological Association Dissertation Award and a Clara Mayo

Dissertation Award. Nicotine and placebo patches were provided by Smith-

Kline Beecham (now GlaxoSmithKline). We thank Stephen T. Tiffany and

Brian Carter for their availability in responding to questions about the

imaginal cue exposure procedures.

Correspondence concerning this article should be addressed to Sandra

Baker Morissette, Veterans Affairs Boston Health Care System, Psychol-

ogy Service (116B), 251 Causeway Street, Boston, MA 02114. E-mail:

[email protected]

Psychology of Addictive Behaviors Copyright 2005 by the American Psychological Association2005, Vol. 19, No. 2, 192198 0893-164X/05/$12.00 DOI: 10.1037/0893-164X.19.2.192

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Indeed, only one published study to date investigated the effects of

transdermal nicotine during exposure to smoking cues (Tiffany,

Cox, & Elash, 2000). Although this study did not examine the

influence of transdermal nicotine on anxiety, it did investigate the

effects of transdermal nicotine on negative affect, a broader con-

struct that can include anxiety (Brown, Chorpita, & Barlow, 1998).

In Tiffany et al.s (2000) study, participants completed two cuereactivity sessions separated by 6 hr. During each session, they

were exposed to both imaginal and in vivo cues, containing either

smoking or neutral content. Participants were unmedicated during

the first session and wore either a nicotine (21 mg) patch or

placebo patch during the second session. Overall, smoking urge

increased in both patch groups across the 6-hr experimental period,

but significantly more so in the placebo group. The placebo group

also experienced increases in negative mood levels across the 6-hr

experimental period, whereas the nicotine group experienced no

change in negative mood. With regard to the cue reactivity trials,

cigarette stimuli generated greater negative affect ratings than

neutral stimuli, but no significant interaction effects were observed

by patch type. Participants reported significantly more craving in

response to cigarette cues than in response to neutral cues, regard-less of patch type. During the second session, the nicotine group

reported lower craving levels across each of the cigarette and

neutral trials. However, a comparison of changes in craving in

response to cigarette and neutral cues across the two sessions

revealed that the placebo group experienced an increase in craving,

whereas the nicotine group experienced no change in craving

reactivity to the cues. Thus, although nicotine appeared to reduce

craving elicited by deprivation, it did not have a significant impact

on craving elicited by the smoking cues.

The current study expanded on Tiffany et al.s (2000) research

by incorporating explicit mood triggers into the experimental

paradigm and by specifically examining the effects of transdermal

nicotine on anxiety responses. Our primary aim was to evaluatewhether transdermal nicotine would attenuate smoking urge and

anxiety in response to smoking and anxiety cues. We predicted that

if this were true, then nicotine-deprived smokers (placebo) would

have a greater urge and anxiety responses to the imaginal cues than

nondeprived (nicotine) smokers. Although Tiffany et al. did not

find that the nicotine patch selectively inhibited urge or negative

affect responses to smoking cues, this has not been examined with

anxiety ratings or when participants are confronted with specific

anxiety cues. An accumulating body of research suggests that

nicotine can be anxiolytic when administered via cigarettes, but

this has yet to be established with transdermal nicotine.

MethodParticipants and Design

Participants were undergraduate, daily smokers who were recruited

through flyers and newspaper and Web site advertisements distributed

throughout local universities and the community. Participants were

screened by telephone to determine inclusion and exclusion criteria. Par-

ticipants were eligible if they were at least 18 years of age, daily moderate

to heavy smokers (1540 cigarettes per day [cpd]), not currently consid-

ering quitting or changing their smoking (to minimize fluctuations in daily

smoking), and willing to deprive themselves of smoking during the study

and wear a nicotine or placebo patch. Participants were excluded if they

had a previous history of using the nicotine patch; endorsed a medical

history that contraindicated use of the nicotine patch (e.g., heart disease,

high blood pressure, allergy to adhesive tape, pregnancy); or were currently

taking anxiolytics, antidepressants, cardiac medications (e.g., beta block-

ers), asthma medication, or over-the-counter diet medications. Participants

were also ruled out for possible alcohol or substance disorders by scoring

6 or higher on the Drug Abuse Screening Test (Skinner, 1982) or greater

than 12 on the Alcohol Dependence Scale (Skinner & Allen, 1982).

Finally, participants who endorsed current Axis I disorders were excluded.A diagnostic interview (described below) conducted during the course of

the assessment determined final eligibility. On the basis of this interview,

2 participants who had multiple comorbid diagnoses were excluded with

replacement. Both received a placebo patch. One additional participant,

who had received a nicotine patch, was discontinued from the study when

she became ill (i.e., vomited) during the assessment. Thus, of the 55

undergraduate, daily smokers who participated in the study, 52 were

included in the final analyses (26 per patch group).

No significant differences were observed between patch groups on

demographic characteristics. Overall, participants were largely Caucasian

(78.9%; Asian, 11.5%; Latino, 9.6%) and had an average age of 20.6 years

(SD 1.7). Gender was evenly distributed across groups (female

55.8%). Participants smoked an average of 19.8 cigarettes per day (SD

4.2) for 5.1 years (SD 3.1), and had made 2.1 quit attempts (SD 2.6).

A 2 2 2 mixed, between- and within-subjects design was used, withpatch group (nicotine vs. placebo) as the between-subjects factor and

anxiety cues (presence or absence) and smoking cues (presence or absence)

as the within-subject factors.

Measures and Apparatus

Pre- and postpatch absorption measures. Prior to and following a 4-hr

patch absorption period (or nicotine deprivation period, in the case of the

placebo group), participants completed measures of urge and withdrawal.

Replicating Tiffany et al. (2000), we administered the Questionnaire of

Smoking Urges (QSU; Tiffany & Drobes, 1991) and the Smoking With-

drawal Questionnaire (SWQ; Shiffman & Jarvik, 1976). The QSU is a

32-item measure that comprises two factors demonstrating good internal

consistency: Factor 1 includes items related to intention/desire to smoke

and anticipation of pleasure. Factor 2 includes items related to anticipationof relief of negative affect/withdrawal and urgent desire to smoke. The

SWQ is a 25-item measure containing four factors, including Stimulation,

Desire to Smoke, Physical Symptoms, and Psychological Symptoms. Par-

ticipants also completed ratings of current anxiety on a Likert scale that

ranged from 0 (none) to 100 (as intense as imaginable). This single-item

measure of anxiety is commonly used in the anxiety literature (e.g., Craske,

Street, & Barlow, 1989; Turner, Beidel, & Jacob, 1994; Wilhelm & Roth,

1997) and was chosen because of the studys use of multiple assessments.

Patch absorption/deprivation period. Several measures were adminis-

tered during the first half of the 4-hr patch absorption/deprivation period to

assess stable smoking and anxiety characteristics. The Anxiety Disorders

Interview ScheduleIV (Brown, DiNardo, & Barlow, 1994) was admin-

istered to verify absence of current anxiety, mood, or substance disorders.

Separate analyses exploring interrater reliability of the Anxiety Disorders

Interview ScheduleIV have shown good to excellent diagnostic agree-

ment (Brown, DiNardo, Lehman, & Campbell, 2001). Self-report measures

were selected from those used extensively in past research using imaginal

cue reactivity procedures (e.g., Drobes & Tiffany, 1997; Tiffany et al.,

2000) for comparability across studies. The Fagerstrom Test for Nicotine

Dependence (FTND; Heatherton, Kozlowski, Frecker, & Fagerstrom,

1991) is a 6-item measure of nicotine dependence that has demonstrated

convergent validity with biochemical indices of heaviness of smoking. An

18-item measure identifying various types of smoking, the Reasons for

Smoking Questionnaire (Ikard, Green, & Horn, 1969) includes six factors

with good internal consistency: (a) Habitual, (b) Addictive, (c) Negative

Affect Reduction, (d) Pleasurable Relaxation, (e) Stimulation, and (f)

Sensorimotor Manipulation. Although the construct validity of this mea-

193TRANSDERMAL NICOTINE DURING IMAGINAL CUE EXPOSURE

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sure has been questioned (Shiffman, 1993), we chose it for its compara-

bility to Tiffany et al. (2000). The Affect Intensity Measure (Larsen &

Diener, 1987) is a 40-item measure of strength of affective reactions with

good testretest reliability and convergent validity. The Questionnaire

Upon Mental Imagery (Sheehan, 1967) contains 35 items designed to

measure a persons ability to use imagery in seven sensory modalities

(visual, auditory, cutaneous, kinaesthetic, gustatory, olfactory, and

organic).Postexposure trial ratings. Following each exposure, participants

completed a 10-item, brief version of the QSU (QSUBrief; Cox, Tiffany,

& Christen, 2001) to determine how they responded during the most recent

exposure scenario. This measure has high internal consistency and a factor

structure similar to that of the QSU (Tiffany & Drobes, 1991). We selected

the briefer version to facilitate repeated assessment. Participants also

completed average anxiety ratings experienced during the script using a

0-to-100-point scale (0 none, 100 as much as imaginable). Vividness

ratings were obtained to measure how clearly participants were able to

imagine the scripts (0-to-100-point scale; 0 not vivid at all, 100

extremely vivid).

Procedure

Participants attended one experimental session that lasted 6.5 hr. They

were each paid $70 for their participation plus an additional $5 reimburse-

ment for lunch. At the start of each session, participants completed an

informed consent form. They then smoked one cigarette and waited a

standardized period of 30 min, at the end of which a nicotine (21 mg; n

26) or placebo (n 26) patch was randomly applied to the upper dominant

smoking arm in a double-blind fashion. A Nicoderm 21 mg patch (Smith-

Kline Beecham, now GlaxoSmithKline; Research Triangle Park, NC) was

used. Participants then waited a period of 4 hr (nicotine absorption/

deprivation period). The 4-hr absorption period was selected on the basis

of the manufacturers suggestions of a period of 2 hr to 4 hr for transdermal

nicotine to reach constant levels in the blood (Physician Representative,

SmithKline Beecham [now GlaxoSmithKline], personal communication,

December 14, 1999). During the first half of the nicotine absorption/

deprivation period, a diagnostic interview was conducted, and self-reportmeasures were completed. Participants were allowed to read, study, or

watch a movie during the remaining time.

The exposure procedures were based on those validated by Tiffany and

Drobes (1990). After the absorption period, participants were seated in a

reclining chair. A white-noise machine was used to minimize outside noise

during the imaginal procedures. The scripts were then presented over

headphones. Participants listened to and imagined each of the scripts with

their eyes closed. For demonstration purposes, a practice script was first

presented. Four types of experimental imagery scripts were then presented:

(a) anxiety plus smoking cues, (b) anxiety cues alone, (c) smoking cues

alone, and (d) neutral cues. Two scripts of each type were used, totaling

eight imaginal scenarios. Scripts were counterbalanced for both order and

sequence. Each script sequence consisted of a 30-s baseline period, 50-s

script presentation period, and 30 s of active imagery by the participant

terminated with the word stop. Participants were then asked to open their

eyes and complete postexposure trial questionnaires asking them about

how they felt during the most recent scenario.

The scripts were selected from a series of scripts developed by Maude-

Griffin and Tiffany (1996). Scenarios that contained anxiety content (i.e.,

words such as tense, anxious, and worried) were specifically chosen

from the series of negative affect scripts. The scripts were slightly modified

from the originals by Maude-Griffin and Tiffany and are available from

Sandra Morissette. Specifically, words that suggested presence or degree of

urge were removed (e.g., your desire to smoke grows stronger and

stronger, your desire to smoke does not seem to be going away). In

addition, words and phrases in the neutral scripts that might have suggested

an anxiety response (e.g., suddenly, and your fingers slip) were omit-

ted. Pilot testing of the revised scripts indicated that they effectively

induced anxiety (vs. depression, anger, or other mood). After presentation

of the scripts, the patch was removed. To assess the integrity of the

double-blind procedure, participants and the clinician were then asked to

guess whether they had received a nicotine patch or a placebo patch.

Data Analyses

Ratings from each of the two script presentations from each category

were averaged to create dependent measures of responses to the four script

types (smoking plus anxiety, anxiety, smoking, neutral). The primary

data-analytic strategy focused on the effect of the nicotine patch on

measures of cue reactivity. We conducted separate 2 2 2 (Group

Smoking Cues Anxiety Cues) mixed-design analyses of variance to

analyze the study hypotheses using each of the postexposure trial measures.

Results

Manipulation Check

Double blind. We calculated percentage accuracy scores to

determine whether participants and the investigator were able to

accurately guess whether the participant had received a nicotine

patch or a placebo patch. Participants and the investigator were

accurate 53.8% and 65.4% of the time, respectively. Thus, the

medication blind appeared to be adequately maintained.

Vividness. Comparisons between patch groups across script

types were conducted to ensure that the results could not be

attributed to differences in how clearly participants were able to

imagine the scripts. Results did not support differences between

patch groups in script vividness ratings (Patch Smoking

Anxiety), F(1, 50) 0.45, p .50, supporting the equivalence of

the imaginal procedures for both groups. Average vividness scores

for each of the scripts (100 extremely vivid) were as follows:

anxiety plus smoking cues: 74.8, SD 14.0; anxiety cues alone:

78.0, SD 13.4; smoking cues alone: 80.6, SD 14.0; andneutral cues: 75.4, SD 15.7.

Anxiety manipulation. We conducted paired samples t tests to

determine whether the anxiety script sufficiently induced anxiety

in comparison to the neutral script. Scripts that included smoking

cues were not included in this analysis because previous studies

have demonstrated that smoking cues are also powerful elicitors of

negative affect (e.g., Burton & Tiffany, 1997). Average anxiety

ratings were significantly higher in response to the anxiety script

than in response to the neutral script, t(51) 11.70, p .01 (Ms

50.8 and 14.6 for the anxiety and neutral scripts, respectively).

Thus, the anxiety script appeared to elicit moderate levels of

anxiety, supporting the anxiety-inducing utility of the script.

Between-Groups Differences

Smoking characteristics are presented in Table 1, along with

relevant indices of affect intensity and mental imagery ability. No

significant differences were observed between patch groups on

smoking characteristics, strength in affective reactions, or mental

imagery ability.

Patch Absorption/Deprivation Phase

Mean scores and standard deviations of measures completed

prior to and following the patch absorption phase are presented in

194 MORISSETTE, PALFAI, GULLIVER, SPIEGEL, AND BARLOW

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Table 2. We conducted repeated measures analyses of variance to

determine whether the nicotine and placebo groups differed sig-

nificantly on measures prior to and following the 4-hr patch

absorption/deprivation phase. Before patch administration and the

absorption phase, the two groups did not significantly differ on any

measures. Significant Patch (nicotine vs. placebo) Time (pre-

vs. postabsorption) interactions were found for desire to smoke/

anticipation of pleasure (QSU Factor 1), F(1, 50) 9.44, p .01;craving (SWQ Craving subscale), F(1, 49) 12.07, p .01;

physical symptoms (SWQ Physical Symptoms subscale), F(1,

50) 5.27, p .05; and stimulation/sedation (SWQ/Stimulation

Sedation subscale), F(1, 50) 4.21, p .05. Specifically, ratings

on QSU Factor 1 and the SWQ Craving subscale increased over

time in both groups, but to a greater magnitude in the placebo

group. In comparison, the SWQ Physical Symptoms and

StimulationSedation subscales increased over time in the nicotine

group, but decreased in the placebo group. The symptomatic

increase in the nicotine group may be a product of its stimulantproperties (e.g., leading to endorsement of increased heart rate, vs.

decreased heart rate in the placebo group due to withdrawal; Carter

& Tiffany, 1999). A significant two-way interaction was not

observed for anxiety ratings, F(1, 50) 0.004, p .95.

Cue Reactivity Indices

Smoking urge. A significant three-way interaction (Patch

Smoking Anxiety) was found, F(1, 50) 5.79, p .05, for

smoking urge, as measured by the QSUBrief (see Figure 1, left

panel). We conducted follow-up tests using interaction contrasts to

examine the nature of the three-way interaction. We used a mod-

ified Bonferroni technique (Holland & Copenhaver, 1988) to con-

trol for error related to conducting multiple follow-up contrasts.

Results indicated that both the Patch Smoking interaction, F(1,

50) 2.97, p .09, and the Patch Anxiety interaction, F(1,

50) 1.13, p .29, were nonsignificant. However, significant

Smoking Anxiety interactions were found within both the

nicotine group, F(1, 25) 44.91, p .001, and the placebo group,

F(1, 25) 20.32, p .001. These findings suggest that the

presence of anxiety cues moderated the effect of smoking cues on

urge response, although the overarching three-way interaction

indicated that the nature of this interaction differed by patch group.

Thus, patch group did not alter response to each cue alone (as per

nonsignificant Patch Smoking and Patch Anxiety interac-

tions) but, rather, moderated the interaction between smoking and

anxiety cues.We also conducted t-test comparisons to determine whether

there were between-groups differences in absolute levels of urge

response to the script types. No significant differences were ob-

Table 1

Means of Smoking Characteristics and Other Measures by

Patch Status

Index

Nicotine(n 26)

Placebo(n 26)

M SD M SD

CSR nicotine abuse/dependence 2.4 1.4 3.0 1.5FTND 3.7 1.8 4.2 1.7RFS

Nicotine 17.6 4.8 16.6 3.7Habitual 16.4 3.8 15.2 3.1Psychological 23.0 3.5 21.7 3.4

AIM 3.7 0.46 3.5 0.43QMI 2.5 0.78 2.4 0.69

Note. CSR clinical severity rating (08; 4 or higher clinical diag-nosis, 3 or lower subclinical diagnosis); FTND Fagerstrom Test forNicotine Dependence (Heatherton et al., 1991; range of possible scores 010; higher scores indicate more physical dependence); RFS Reasonsfor Smoking (Ikard et al., 1969; range of possible scores for each scale 630; higher scores indicate more inclination to smoke for nicotine, out ofhabit, or for psychological reasons); AIM Affect Intensity Measure(Larsen & Diener, 1987; range of possible scores 16; higher scoresindicate greater intensity of emotions); QMI Questionnaire of MentalImagery (Sheehan, 1967; range of possible scores 17; lower scoresindicate more imagery vividness).

Table 2

Means of Measures Completed Prior to and Following the Patch Absorption Phase

Measure

Nicotine (n 26) Placebo (n 26)

Pre Post Pre Post

M SD M SD M SD M SD

QSU32Factor 1a 3.36 1.41 4.26 1.23 3.14 1.24 5.09 1.27Factor 2 1.95 0.96 2.65 1.20 2.04 0.81 2.94 0.92

SWQCravingb 3.91 1.22 4.41 1.11 3.70 0.99 5.21 1.08Psych. Discomfort 4.03 0.71 4.10 0.91 4.23 0.77 4.19 0.76Physical Symptomsa 2.17 0.89 2.65 1.19 2.50 0.95 2.33 0.85Stimulation/Sedationa 4.60 1.22 5.00 1.17 4.35 1.30 3.90 1.37

Anxiety 11.54 15.92 23.46 26.37 12.31 13.94 24.62 19.64

Note. QSU32 Questionnaire of Smoking Urges (Tiffany & Drobes, 1991; Factor 1 intention/desire to smoke and anticipation of pleasure; Factor2 anticipation of relief of negative affect/withdrawal and urgent desire to smoke; range of possible scores for each factor: 17; higher scores indicategreater levels of Factors 1 and 2); SWQ Symptom Withdrawal Questionnaire (Shiffman & Jarvik, 1976; range of possible scores: 07; higher scoressignify more withdrawal symptoms present, 4 neutral). Anxiety ratings could range from 0 to 100 (0 none, 100 as much as imaginable).a Significant Patch Time interaction at p .05. b Significant Patch Time interaction at p .01.


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served (all ps .15), suggesting that participants who received a

nicotine patch experienced levels of urge similar to those given a

placebo patch. Thus, transdermal nicotine had no benefit whatso-

ever on alleviating urge in response to smoking and anxiety cues.

Anxiety/negative affect. Ratings of anxiety exhibited a differ-

ent pattern (see Figure 1, right panel). The three-way interaction

(Patch Smoking Anxiety), F(1, 50) 1.51, p .23, was not

significant. Two-way Patch Smoking, F(1, 50) 2.38, p .13,

and Patch Anxiety interactions, F(1, 50) 1.91, p .17, were

also not supported for anxiety ratings, suggesting that patch con-

dition did not moderate the effects of smoking and anxiety cues on

anxiety levels. As with urge, a significant Smoking Anxiety

Cues interaction was found, F(1, 51) 45.73, p .01. As can beseen in Figure 1 (right panel), scripts that contained specific

anxiety cues elicited greater anxiety ratings than scripts that con-

tained either smoking or neutral cues, supporting the utility of the

anxiety scripts in inducing anxiety. Moreover, smoking cue scripts

also induced anxiety, albeit less so than scripts that contained

explicit anxiety cues. No significant differences were observed

between patch groups by script type (all ps .33).

Discussion

Consistent with previous work (Tiffany et al., 2000), the nico-

tine patch attenuated urge related to deprivation. As can be seen in

Table 2, the nicotine group reported lower levels of craving (SWQ)

and desire to smoke/anticipation of pleasure (QSU Factor 1) thanthe placebo group following the 4-hr nicotine absorption/depriva-

tion period. However, transdermal nicotine did not alleviate all

forms of urge; specifically, anticipation of relief of negative affect/

urgent desire to smoke (QSU Factor 2) did not vary by patch

condition over the course of the absorption/deprivation period.

Correspondingly, although an increase in negative affect is a

common feature of nicotine withdrawal (Piasecki, Kenford, Smith,

Fiore, & Baker, 1997), anxiety ratings did not differ between patch

groups. Both groups experienced a mild increase in anxiety levels

from pre- to postabsorption. This finding was inconsistent with

results from Tiffany et al. in which only individuals in the placebo

group, but not in the nicotine group, experienced an increase in

negative affect. However, Tiffany et al.s study included a depri-

vation period of 6 hr, a longer withdrawal period than in the

current study, which may account for the observed increase in

negative affect in the placebo group. In addition, Tiffany et al.

assessed negative affect in general rather than focusing explicitly

on anxiety. Thus, differences may have been observed in the

Tiffany et al. study due to the higher order construct of negative

affect that was used, one component of which may have been

anxiety.

Transdermal nicotine did not significantly alleviate smoking

urge during the cue reactivity procedures. Despite the significant

three-way interaction, no differences were observed between

scripts by patch group. Thus, when exposed to smoking-relevant

stimuli (smoking and anxiety cues), any urge-attenuating effects of

the nicotine patch were virtually eliminated. This finding is note-

worthy given the observed (and expected) statistically significant

differences between patch groups in craving and desire to smoke

prior to beginning the cue reactivity procedures (i.e., post nicotine

absorption/deprivation period). Despite these differences, the pla-

cebo group did not respond with greater reactivity to smoking and

anxiety cues. Moreover, the nicotine group, which started with

lower urge levels before the cue reactivity procedures, responded

with similar levels of urge in response to the cues, suggesting that

nicotine actually had a greater relative increase in urge frombaseline. It is notable that the postabsorption period urge (QSU)

was not used as a covariate when analyzing urge response, because

this would violate the assumptions of analysis of covariance.

Transdermal nicotine had no superior effect over a placebo in

alleviating anxiety response to smoking and anxiety cues. Regard-

less of patch status, scripts that contained explicit anxiety cues or

smoking plus anxiety cues elicited greater anxiety ratings than

scripts that contained only smoking cues or neutral cues. These

findings support the ability of the scripts to induce anxiety. More-

over, the smoking cue script, which contained no mention of

anxiety, elicited greater anxiety ratings than neutral scripts, indi-

Figure 1. Average Questionnaire of Smoking UrgesBrief (QSU-Brief) and anxiety scores by patch and script

type.


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cating that smoking cues alone were able to elicit anxiety, albeit

less so than scripts containing specific anxiety cues.

Several important similarities and differences have emerged

between the current study and the findings of Tiffany et al. (2000),

the only other published study to date that examined the acute

effects of transdermal nicotine during cue reactivity. Both studies

found statistically significant effects of nicotine in alleviating urgerelated to general smoking deprivation. This effect is consistent

with other studies that have found an attenuating effect of nicotine

on abstinence-related smoking urge (Leischow et al., 1997; Rose,

Herskovic, Trilling, & Jarvik, 1985). With regard to the cue

reactivity procedures, Tiffany and his colleagues found that the

nicotine patch produced significantly lowerlevels of smoking urge

than the placebo group across all stimulus trials, although there

was no selective effect of nicotine on cue reactivity. This stands in

contrast to current findings, in which the nicotine group produced

equivalent levels of urge response as the placebo group across all

script types. These discrepant findings may be due to the differing

deprivation periods in the two studies (i.e., 2 hr longer in Tiffany

et al.s study), the use of different cue content, or both. Moreover,

the samples of the two studies were subtly but importantly differ-ent, which may have driven the dissimilar responses to the cues,

the transdermal nicotine, or both. Whereas the current study in-

cluded college smokers (average age: 20.65 years) who smoked an

average of 19.8 cpd, and had an average FTND score of 3.95, the

average participant in Tiffany et al.s study was 31.5 years old,

smoked 29 cpd, and had an FTND score of 4.90. Previous studies

have shown that individuals with higher levels of nicotine depen-

dence exhibit greater urge responses to cues than those with low

nicotine dependence (Payne & Smith, 1990). Consequently, smok-

ers in Tiffany et al.s study, who were more dependent, may have

responded differently to the cues when given transdermal nicotine

versus being in a state of nicotine deprivation (i.e., placebo group).

Additionally, differences in vividness ratings between the studiesmay have accounted for variability in findings. Although no sig-

nificant between-groups differences in vividness were found

across scripts in the current study, Tiffany et al. found that partic-

ipants who received nicotine rated scripts as more vivid. Finally,

scripts in the current study were modified slightly to control for

demand characteristics. Although the scripts were pilot tested to

ensure induction of smoking urge and anxiety, these small changes

could have accounted for differences between studies. Note that it

is unlikely that demand characteristics alone could explain the

complex patterns of results found (e.g., differing patterns of urge

response to script types within patch groups).

There are several limitations to the current study that warrant

notation. First, a nondeprived/no-patch control group was not

included, which prevents analysis of response to the cue reactivityparadigm without a nicotine or placebo patch. Second, although

for conceptual reasons the data were analyzed as a 2 2 2

design, technically it is not such a design, in that the four cue

conditions were independent of one another (i.e., separate scenar-

ios were used for each condition). Future research might use a true

2 2 2 design by using identical cues and varying their

presence or absence with alternative cues. Third, we examined

urge during a single absorption/deprivation period and during cue

reactivity. Future research might use an alternating treatments

design (e.g., ABAB, in which cues are added and removed sys-

tematically; Hayes, Barlow, & Nelson-Gray, 1999) to ascertain the

effects of nicotine over time during the fluctuating presence versus

absence of cues. Fourth, the sample included college smokers who

were not trying to quit smoking, which affects generalizability.

College smokers may be different from postcollege smokers or

from individuals who have differing educational backgrounds

(Pierce, Fiore, Novotny, Hatziandreu, & Davis, 1989). Replication

of the current findings with other samples is an important task forthe future. Fifth, anxiety was measured using a single-item scale.

It is possible that differences in patterns of responding between

urge and anxiety could be a function of differences in the psycho-

metrics between these two measures. A single-item Likert scale

was chosen because of the repeated assessment design. Prior

research indicates that, when using relatively intuitive constructs,

single-item indices are as informative as multi-item scales

(Burisch, 1984; Carver, Meyer, & Antoni, 2000). In support of the

use of the single-item index of anxiety, this measure clearly

distinguished between scripts that contained anxiety cues versus

neutral-content scripts. Future research should develop and inves-

tigate the use of brief, multi-item, moment-to-moment anxiety

measures. Finally, because the study involved repeated exposure to

cues in close succession, carryover effects from preceding cuesmay have influenced subsequent cues. Participant fatigue from

imagining several scenarios may have also affected cue reactivity.

Methods for controlling carryover effects and participant fatigue in

such paradigms deserve consideration in future research.

In summary, transdermal nicotine attenuated some forms of urge

following the patch absorption phase but had no beneficial effect

over a placebo in alleviating smoking urge or anxiety in response

to explicit smoking and anxiety cues. Individuals who received the

nicotine patch still experienced moderate to strong levels of reac-

tivity across measures in response to all smoking and anxiety cue

scripts. Although possible, it seems unlikely that these small or

nonsignificant findings were due to participants being underdosed.

First, the 4-hr nicotine absorption period was chosen on the basisof the manufacturers suggestions for nicotine to reach constant

levels. Second, scores on the QSU and SWQ after the absorption

period were similar to those reported in Tiffany et al.s (2000)

study, which used a 6-hr absorption period, suggesting comparable

levels of urge and craving across the two time frames. Whether cue

reactivity differs with prolonged use of the nicotine patch would be

important to investigate. Nonetheless, findings from the current

study are informative for smokers who are initiating their quit

attempts. Future research is also needed to examine the influence

of other forms of negative affect (e.g., anger, depression) on

smoking response during nicotine replacement. Understanding the

effects of mood during use of transdermal nicotine may be impor-

tant for developing treatment and relapse prevention programs,

particularly for smokers with comorbid psychiatric disorders.

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Received December 4, 2003

Revision received March 31, 2004

Accepted April 7, 2004


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