Nicotine-dependent Cigarette Smokers Research Articles

The associations between cigarette smoking behavior and the use of heated tobacco products among Arab cigarette smokers: Findings from Saudi Arabia, Egypt, Kuwait, and Yemen

As the availability of tobacco forms has evolved, emerging products known as heated tobacco products (HTPs) are increasingly being consumed worldwide and are claimed to be less harmful than tobacco cigarette smoking. To date, it is unknown whether Arab cigarette smokers are using or susceptible to HTPs. Therefore, this study aimed to assess the association between cigarette smoking behavior and the use of and susceptibility to HTPs in the Eastern Mediterranean region. Arab cigarette smokers (n = 628) from Saudi Arabia, Egypt, Kuwait, and Yemen were recruited using a convenience sampling technique. A cross-sectional survey comprised questions related to sociodemographic characteristics, cigarette smoking behavior characteristics (quitting attempts and desire to quit cigarette smoking, nicotine dependence, and consideration of switching to nicotine products with reduced health risks), and awareness of, use of, and susceptibility to use of HTPs. Descriptive and logistic regression models were used for analysis. The participants indicated a high frequency of past quitting attempts and a desire to quit smoking cigarettes. They were also considering switching to a nicotine product with reduced health risks. However, their awareness of HTPs was relatively low (24.2%), and the proportion of participants who had ever used HTPs or were currently using them was quite low as well (10.7% and 5.0%, respectively). A history of quit attempts was associated with more likely lifetime use of HTPs (adjusted odds ratio [AOR] = 2.63, 95% confidence interval [CI] [1.21–5.71]). Nicotine-dependent cigarette smokers were more likely to be susceptible to HTP use (AOR = 1.12, 95% CI [1.01–1.24]). Moreover, those who would consider switching to a product that provided nicotine and could reduce health risks by 99% were more likely to be susceptible to using HTPs (AOR = 2.17, 95% CI [1.05–4.51]). Awareness of HTPs is relatively low among Arab cigarette smokers. Attempts to quit cigarette smoking, nicotine dependence, and the consideration of switching to a product that delivers nicotine with reduced health risks were significantly associated with using HTPs. The findings of this study provide potential for evidence-based treatment for smokers and will help prevent the use of tobacco industry tactics in marketing HTPs.

Cigarette craving modulation is more feasible than resistance modulation for heavy cigarette smokers: empirical evidence from functional MRI data.

Modulation of cigarette craving and neuronal activations from nicotine-dependent cigarette smokers using real-time functional MRI (rtfMRI)-based neurofeedback (rtfMRI-NF) has been previously reported. The aim of this study was to evaluate the efficacy of rtfMRI-NF training in reducing cigarette cravings using fMRI data acquired before and after training. Treatment-seeking male heavy cigarette smokers (N = 14) were enrolled and randomly assigned to two conditions related to rtfMRI-NF training aiming at resisting the urge to smoke. In one condition, subjects underwent conventional rtfMRI-NF training using neuronal activity as the neurofeedback signal (activity-based) within regions-of-interest (ROIs) implicated in cigarette craving. In another condition, subjects underwent rtfMRI-NF training with additional functional connectivity information included in the neurofeedback signal (functional connectivity-added). Before and after rtfMRI-NF training at each of two visits, participants underwent two fMRI runs with cigarette smoking stimuli and were asked to crave or resist the urge to smoke without neurofeedback. Cigarette craving-related or resistance-related regions were identified using a general linear model followed by paired t-tests and were evaluated using regression analysis on the basis of neuronal activation and subjective craving scores (CRSs). Visual areas were mainly implicated in craving, whereas the superior frontal areas were associated with resistance. The degree of (a) CRS reduction and (b) the correlation between neuronal activation and CRSs were statistically significant (P < 0.05) in the functional connectivity-added neurofeedback group for craving-related ROIs. Our study demonstrated the feasibility of altering cigarette craving in craving-related ROIs but not in resistance-related ROIs via rtfMRI-NF training.

A double-blind randomized clinical trial of high frequency rTMS over the DLPFC on nicotine dependence, anxiety and depression

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is a widely applied treatment protocol for chronic smoking and major depressive disorder. However, no previous study has measured the effects of rTMS on both nicotine consumption and anxiety/depression in the same volunteers despite the relationship between them. The aim of this work was to evaluate the efficacy of 10 daily sessions of HF-rTMS over the L-DLPFC in chronic cigarette smokers’ addiction and investigate the possible beneficial effects of this treatment procedure on symptoms of depression and anxiety in the same subjects. The study included 40 treatment-seeking nicotine-dependent cigarette smokers. Onset/duration of smoking, number of cigarettes/day, Fagerstrom Test of Nicotine Dependence (FTND), Tobacco Craving Questionnaire-Short Form (TCQ-SF), Hamilton depression and anxiety scales (HAM-D and HAM-A) were recorded. Participants were randomly assigned to the active or the sham treatment group. Those in the active group received 10 trains of 20 Hz stimulation, at 80% of the resting motor threshold (rMT) for 10 consecutive working days over L-DLPFC. Participants were reassessed immediately after treatment, and then 3 months later using all rating scales. There were no differences between active and sham groups at baseline. The cigarette consumption/day, and scores on FTND, and TCQ decreased significantly in both groups (p = 0.0001 for each) immediately after treatment. However, improvement persisted to 3 months in the active group but not in the sham group. Moreover, there was a significant reduction in HAM-D and HAM-A scores immediately after treatment in the active but not the sham group. Subjects with a longer history of smoking had a lower percent improvement in FTND (p = 0.005). Our findings revealed that HF-rTMS over L-DLPCF for 10 days reduced cigarette consumption, craving, dependence, and improved associated symptoms of anxiety and depression.ClinicalTrials.gov Identifier: NCT03264755 registered at 29/08/2017.

Striato-cortical tracts predict 12-h abstinence-induced lapse in smokers.

Striatal circuit dysfunction is implicated in smoking behaviors and lapses during abstinence attempts. However, little is known about whether the structural connectivity of striatal tracts can be used to predict abstinence-induced craving and lapses. The tract strengths of striatal circuits were compared in 53 male nicotine-dependent cigarette smokers and 58 matched nonsmokers, using seed-based classification by diffusion tensor imaging (DTI) probabilistic tractography with 10 a priori target masks. A 12-h abstinence procedure was then employed, after which 31 individuals abstained and 22 lapsed. Linear regression and binary logistic regression was conducted to test whether the tract strength of frontostriatal circuits was associated with craving changes in abstainers and predicted lapse in smokers. Compared with nonsmokers, in the left hemisphere, smokers showed weaker tract strength in striatum-medial orbitofrontal cortex (mOFC), striatum-ventral lateral prefrontal cortex (vlPFC), striatum-inferior frontal gyrus (IFG) and striatum-posterior cingulate cortex (PCC) (Bonferroni corrected, p < 0.05/20 = 0.0025). In abstainers, the abstinence-induced increases in craving were associated with the tract strength of the left striatum-mOFC and striatum-vlPFC. The tract strength of left striatum-dorsolateral PFC (dlPFC) predicted lapse in smokers with an accuracy of 68.3%. These results provide system-level insights into the weaker tract strength of frontostriatal circuits in male smokers and their potential roles as neuroimaging markers for abstinence-induced craving and risk of lapse. Future studies in female smokers are needed to determine if this generalizes across genders.

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants. We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session. A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS. This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers. rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794).

Use of nicotine replacement therapy in young people entering custody in New South Wales, Australia.

To describe the prevalence of nicotine dependence and acceptance of nicotine replacement therapy (NRT) in young people entering custody, where smoking is not allowed. Cross-sectional study in 2013. All New South Wales Juvenile Justice Centres. Incarcerated youth, aged 12-21 years. gender, age, ethnicity, cannabis use. rates of smoking, cannabis use, nicotine dependence, NRT acceptance. Data were collected from 252 Initial Reception Assessments (90.1% male, 56.3% Aboriginal, mean age 16.6 years ± 1.2 standard deviation). According to Fagerstrom screening, 207 (82.1%) young people smoked cigarettes immediately prior to their current incarceration, and of the smokers, 78 (38.4%) were nicotine dependent. Most young people (76.4%) were also daily cannabis users, with 85.6% of cigarette smokers also using cannabis daily. NRT (as 24-h nicotine patches prescribed for 2 weeks) was offered to 54 nicotine dependent and 7 non-dependent young people. Only 13 (21.3%) young people accepted NRT (all daily cannabis-using males), and only 2 young people completed the full prescription. Reasons for refusing or not completing NRT were a fear of 'weird dreams', sleeping issues or that it was no longer needed. Many young people entering custody are nicotine-dependent cigarette smokers and daily cannabis users, and are at high risk of nicotine withdrawal on abstinence. NRT as patch therapy has poor acceptance in this group, except in young men who are daily cannabis users. Screening for nicotine dependence in high-risk young people should include questions about cannabis use, and alternatives to patch therapy deserve further research.

Self-reported smoking effects and comparative value between cigarettes and high dose e-cigarettes in nicotine-dependent cigarette smokers.

The objective of this experiment was to evaluate the comparative value of cigarettes versus high dose e-cigarettes among nicotine-dependent cigarette smokers when compared with money or use of their usual cigarette brand. The experiment used a within-subject design with four sessions. After baseline assessment, participants attended two 15-min unrestricted smoking sessions: one cigarette smoking session and one e-cigarette smoking session. Participants then attended two multiple-choice procedure (MCP) sessions: a session comparing cigarettes and money and a session comparing e-cigarettes and money. Participants (n=27) had used cigarettes regularly, had never used e-cigarettes, and were not currently attempting to quit smoking. The sample consisted primarily of males (72%), with a mean age of 34 years. When given the opportunity to choose between smoking a cigarette or an e-cigarette, participants chose the cigarette 73.9% of the time. Findings from the MCP demonstrated that after the first e-cigarette exposure sessions, the crossover value for cigarettes ($3.45) was significantly higher compared with the crossover value for e-cigarettes ($2.73). The higher participant preference, self-reported smoking effects, and higher MCP crossover points indicate that cigarettes have a higher comparative value than high dose e-cigarettes among e-cigarette naive smokers.

Withdrawal Symptoms and Nicotine Dependence Severity Predict Virtual Reality Craving in Cigarette-Deprived Smokers.

Virtual reality (VR) has been shown to be effective in eliciting responses to nicotine cues in cigarette smokers. The primary aim of this study was to investigate whether cigarette-deprived smokers would exhibit increased craving and changes in heart rate when viewing cigarette related cues as compared to non-smoking cues in a VR environment, and the secondary aim was to assess the extent to which self-assessed measures of withdrawal and dependence correlated with VR craving. Nicotine-dependent cigarette smokers were recruited for a 2 day study. On Day 1, participants smoked as usual and on Day 2 were deprived from smoking overnight. On both days, participants completed self-assessment questionnaires on withdrawal, craving, and nicotine-dependence. Participants completed a VR session during the cigarette deprivation condition only (Day 2). During this session, they were exposed to active smoking and placebo (non-smoking) cues. The data show that self-reported levels of "craving" (p < .01) and "thinking about cigarettes" (p < .0001) were significantly greater after exposure to the active cues versus non-smoking cues. Significant increases in heart rate were found for 3 of 4 active cues when compared to non-smoking cues (p < .05). Finally, significant positive correlations were found between self-reported craving prior to the VR session and craving induced by active VR cues (p < .01). In this report, active VR cues elicited craving during cigarette deprivation. This is the first study to demonstrate that self-reported craving, withdrawal symptoms, and nicotine dependence severity predict cue-induced craving in the VR setting.

Prize contingency management for smoking cessation: A randomized trial

BackgroundAdjunctive behavioral smoking cessation treatments have the potential to improve outcomes beyond standard care. The present study had two aims: (1) compare standard care (SC) for smoking (four weeks of brief counseling and monitoring) to SC plus prize-based contingency management (CM), involving the chance to earn prizes on days with demonstrated smoking abstinence (carbon monoxide (CO) ≤6ppm); and (2) compare the relative efficacy of two prize reinforcement schedules—one a traditional CM schedule, and the second an early enhanced CM schedule providing greater reinforcement magnitude in the initial week of treatment but equal overall reinforcement. MethodsParticipants (N=81 nicotine-dependent cigarette smokers) were randomly assigned to one of the three conditions. ResultsPrize CM resulted in significant reductions in cigarette smoking relative to SC. These reductions were not apparent at follow-up. We found no meaningful differences between the traditional and enhanced CM conditions. ConclusionsOur findings reveal that prize CM leads to significant reductions in smoking during treatment relative to a control intervention, but the benefits did not extend long-term.

Sex differences in resting state neural networks of nicotine-dependent cigarette smokers

Although several sex differences in nicotine dependence have been identified, the neural mechanisms underlying these sex differences are not clear. The present study examines sex differences in resting-state brain activity using an arterial spin labeling (ASL) perfusion imaging technique. Fifty-one (31 males) sated nicotine-dependent cigarette smokers underwent perfusion functional magnetic resonance imaging during the resting state. Using functionally defined hippocampus/amygdala (HIP/AMY) seed regions, we observed sex differences in correlation strength between the HIP/AMY and the bilateral anterior insula, rostral anterior cingulate cortex, and inferior parietal lobule with females showing stronger functional coupling than males. This pattern of synchronous variations in dynamic cerebral blood flow is consistent with recent models of nicotine dependence, and as such, our findings provide a novel perspective on the neural mechanisms that may contribute to sex differences in nicotine dependence.

Sustained Reduction of Nicotine Craving With Real-Time Neurofeedback: Exploring the Role of Severity of Dependence

Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction. Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerström Test for Nicotine Dependence. When viewing smoking-related images with instructions to "crave," patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving. Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3. This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods.

Orexin A Expression and Promoter Methylation in Patients with Cannabis Dependence in Comparison to Nicotine-Dependent Cigarette Smokers and Nonsmokers

Background: The orexins (hypocretins) are neuropeptides with an origin in the lateral hypothalamus. They have been found to be crucial within the context of drug craving, withdrawal und relapse. Methods: Therefore, orexin A gene expression and promoter methylation in peripheral blood cells of 77 subjects [36 with tetrahydrocannabinol (THC) dependence, 20 nicotine-dependent cigarette smokers and 21 nonsmokers] were assessed by quantitative real-time PCR and methylation-specific digestion PCR. Results: There was a statistically significant difference in orexin A expression between the three groups [p = 0.000, F = 131.4, d.f. = 2, analysis of variance (ANOVA)]. Orexin A gene expression was statistically significantly correlated with the Satisfaction with Life Scale (r = –0.28, p = 0.018), a visual analogue scale of craving (r = 0.734, p = 0.000) and three subscales of the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test, i.e. nicotine consumption (r = 0.388, p = 0.001), alcohol consumption (r = 0.354, p = 0.002) and cannabis consumption (r = 0.783, p = 0.000). The mean promoter methylation (as a percentage) was not statistically related to orexin gene expression. However, there was a statistically significant difference in promoter methylation with regard to body mass index in general (F = 2.37, d.f. = 54, p = 0.016, ANOVA). Conclusions: Orexin might be a possible target in THC as well as nicotine dependence, taking into account the effect of THC on energy homeostasis in the circuit of reward and motivation and its impact on appetite and body weight.

Volitional reduction of anterior cingulate cortex activity produces decreased cue craving in smoking cessation: a preliminary real-time fMRI study

Numerous research groups are now using analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in 'real time'. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real-time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a 'reduce craving' paradigm, participants were instructed to 'reduce' their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate 'increase resistance' paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the 'reduce craving' task (P=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the 'reduce craving' session (P=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the 'increase resistance' session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence.

A double-blind, placebo-controlled, randomized clinical trial of oral selegiline hydrochloride for smoking cessation in nicotine-dependent cigarette smokers

Aim The primary aim of this study was to determine the safety and efficacy of the monoamine oxidase-B (MAO-B) inhibitor selegiline hydrochloride (SEL, l-Deprenyl; Eldepryl ®) as an aid for smoking cessation in cigarette smokers. Methods One hundred and one nicotine-dependent adult cigarette smokers without current psychiatric or substance use disorders participated in this 8-week randomized, double-blind, placebo-controlled trial. Participants received either SEL (5 mg bid, n = 51) or placebo (PLO, n = 50), in combination with brief (<10 min) manualized smoking cessation counseling. The main smoking outcome measures were 7-day point prevalence abstinence at end of trial (EOT), 4-week continuous smoking abstinence at end of trial (CA), and 7-day point prevalence abstinence at 6-month follow-up (6MFU). Abstinence was determined by an absence of self-reported cigarette smoking and biochemically verified by expired breath carbon monoxide and plasma cotinine levels. Results Rates of smoking abstinence did not differ by medication group (EOT: SEL = 16%, PLO = 20%, p = 0.57; CA: SEL = 14%, PLO = 18%, p = 0.56; 6MFU: SEL = 12%, PLO = 16%, p = 0.54). Adverse events were modest and comparable between medication groups. Participants receiving SEL were more likely than those receiving PLO to report dry mouth (25.5% versus 8.2%, p < 0.05). Conclusions Our results suggest that SEL was safe and well-tolerated by adult cigarette smokers, but did not improve smoking abstinence rates compared to PLO.

A preliminary placebo-controlled trial of selegiline hydrochloride for smoking cessation

Background Since dopaminergic mechanisms appear to be involved in nicotine dependence, we studied the safety and efficacy of the monoamine oxidase B inhibitor selegiline hydrochloride compared with placebo for smoking cessation in nicotine-dependent cigarette smokers. Methods Forty subjects with DSM-IV nicotine dependence were randomized to: 1) selegiline hydrochloride (5 mg p.o. twice daily) or 2) placebo in an 8-week trial. Outcome measures included smoking cessation rates, treatment retention, and medication side effects. Results Selegiline hydrochloride increased trial end point (week 8) 7-day point prevalence smoking cessation rates (selegiline hydrochloride, 9/20 [45.0%]; placebo, 3/20 [15.0%], odds ratio = 4.64, 95% CI, 1.02–21.00, p < .05), and smoking cessation rates during the last 4 weeks of the trial (selegiline hydrochloride, 6/20 [30.0%]; placebo, 1/20 [5.0%], odds ratio = 8.14, 95% CI, 0.88–75.48, p = .07) in comparison with placebo. Six-month follow-up 7-day point prevalence smoking cessation rates were reduced compared with trial end point (selegiline hydrochloride, 4/20 [20.0%]; placebo, 1/20 [5.0%], odds ratio = 4.75, 95% CI, 0.48–46.91, p = .18). Treatment retention was similar between drug and placebo groups ( p = .13), and selegiline hydrochloride was well tolerated in cigarette smokers. Conclusions This preliminary study suggests that selegiline (10 mg/day) is safe for use and enhances smoking cessation rates compared with placebo in nicotine-dependent cigarette smokers.

Effects of Smoking Abstinence on Visuospatial Working Memory Function in Schizophrenia

Schizophrenic patients have impairments in cognitive function, including deficits in visuospatial working memory (VSWM). VSWM is mediated, in part, by prefrontal cortical dopamine (DA) function, and dysregulation of prefrontal cortical DA systems may contribute to the pathophysiology of schizophrenia. Nicotine has complex effects on spatial working memory (SWM) in animal studies, with most studies demonstrating enhancement of SWM. Cigarette smoking is highly prevalent in schizophrenia, and these patients may smoke cigarettes to remediate cognitive deficits. The present study examined the effects of acute (<1 week) and prolonged (8–10 weeks) smoking abstinence on VSWM in schizophrenic (n = 23) and control (n = 29) nicotine-dependent cigarette smokers during placebo-controlled smoking cessation trials. Schizophrenic and control smoking patients had significant impairments in VSWM compared to non-smoking controls, after adjusting for differences in age, education and depressive symptoms. Schizophrenic smokers who quit smoking had further impairments in VSWM, and control quitters had improvements in VSWM. Abstinence-induced changes in VSWM varied as a function of gender in controls, but not in schizophrenics. These changes in VSWM appeared to be independent of study medications, and smoking abstinence did not significantly alter performance on the Stroop Color Word Test in either group. These results suggest that smoking abstinence differentially alters VSWM in schizophrenic vs. control smokers, and that cigarette smoking has beneficial effects on VSWM in schizophrenic, but not control, smokers.

The impact of three economic factors on cigarette procurement and consumption

This experiment examined the effects of three economic variables on the number of cigarettes earned in nicotine dependent cigarette smokers: (i) the ‘price’ of the cigarettes, (ii) the magnitude of an alternative, monetary reinforcer, and (iii) the ‘openness’ of the cigarette economy. In a laboratory study, smokers earned cigarettes and money by responding on two concurrent random-ratio schedules. Varying the number of responses required on the cigarette schedule varied cigarette price within sessions. Varying the amount of money that could be earned on the money schedule varied the magnitude of the monetary reinforcer between sessions. Varying the number of ‘free’ cigarettes provided after the task varied openness of the cigarette economy between sessions. Analyses revealed that fewer cigarettes were earned as the price of cigarettes increased, and this effect was more pronounced when the alternative monetary reinforcer was large and when free cigarettes were available. We conclude that the decline in the number of cigarettes earned as cigarette price increased was directly related to the availability of substitutes for the earned cigarettes. © 1998 John Wiley & Sons, Ltd.