Toward reducing racialized pain care disparities: Approaching cannabis research and access through the lens of equity and inclusion.

There is growing interest in cannabis use for cancer pain. This commentary aims to discuss the evidence surrounding cannabis use for cancer pain in the context of the long-racialized landscape of cannabis policies and the disparity in pain control among cancer patients holding minoritized racial identities. Much evidence surrounding both the benefits and harms of cannabis use in cancer patients, and all patients in general, is lacking. Although drawing on the research in cancer that is available, it is also important to illustrate the broader context about how cannabis' deep roots in medical, political, and social history impact patient use and health care policies. There are lessons we can learn from the racialized disparities in opioid risk mitigation strategies, so they are not replicated in the settings of cannabis for cancer symptom management. Additionally, the authors intentionally use the term "cannabis" here rather than "marijuana.: In the early 1900s, the lay press and government popularized the use of the word "marijuana" instead of the more common "cannabis" to tie the drug to anti-Mexican prejudice.

Self-reported knowledge of tetrahydrocannabinol and cannabidiol concentration in cannabis products among cancer patients and survivors.

PURPOSE: Cannabis use may introduce risks and/or benefits among people living with cancer, depending on product type, composition, and nature of its use. Patient knowledge of tetrahydrocannabinol (THC) or cannabidiol (CBD) concentration could provide information for providers about cannabis use during and after treatment that may aide in risk and benefit assessments. This study aimed to examine knowledge of THC or CBD concentration among patients living with cancer who consume cannabis, and factors associated with knowledge of cannabinoid concentrations. METHODS: People living with cancer who consumed cannabis since their diagnosis (n = 343) completed an anonymous, mixed-mode survey. Questions assessed usual mode of delivery (MOD), knowledge of THC/CBD concentration, and how source of acquisition, current cannabis use, and source of instruction are associated with knowledge of THC/CBD concentration. Chi-square and separate binary logistic regression analyses were examined and weighted to reflect the Roswell Park patient population. RESULTS: Less than 20% of people living with cancer had knowledge of THC and CBD concentration for the cannabis products they consumed across all MOD (smoking- combustible products, vaping- vaporized products (e-cigarettes), edibles-eating or drinking it, and oral- taking by mouth (pills)). Source of acquisition (smoking-AOR:4.6, p < 0.01, vaping-AOR:5.8, p < 0.00, edibles-AOR:2.6, p < 0.04), current cannabis use (edibles-AOR:5.4, p < 0.01, vaping-AOR: 11.2, p < 0.00, and oral-AOR:9.3, p < 0.00), and source of instruction (vaping only AOR:4.2, p < 0.05) were found to be variables associated with higher knowledge of THC concentration. CONCLUSION: Self-reported knowledge of THC and CBD concentration statistically differed according to MOD, source of acquisition, source of instruction, and current cannabis use.

The Impact of the COVID-19 Pandemic on Stress, Isolation, Smoking Behaviors, and Motivation to Quit in People with HIV Who Smoke.

People with HIV (PWH) smoke at higher rates compared with the general population and have lower cessation rates. The primary aim of this study was to examine the impact of the COVID-19 pandemic on smoking in PWH. A survey was administered to participants in two smoking cessation trials in the United States. Mean cigarettes per day was 13.9 (SD 8.6), and participants reported they had smoked on average for 30.93 years (SD 10.4). More than half (55.7%) of participants (N = 140) reported not changing their smoking during the pandemic, while 15% reported decreasing, and 25% reported increasing their smoking. In bivariate analyses, worrying about food due to lack of money (χ2 = 9.13, df 2, p = 0.01) and greater Covid-related worry (rs = 0.19, p = 0.02) were significantly associated with increased smoking. Qualitative research may be needed to more clearly elucidate factors related to smoking behaviors among PWH.

Brain and cortisol responses to smoking cues are linked in tobacco-smoking individuals.

Cues associated with smoking can induce relapse, which is likely driven by cue-induced neurobiological and physiological mechanisms. For instance, greater relapse vulnerability is associated with increases in cue-induced insula activation and heightened cortisol concentrations. Determining if there is a link between such cue-induced responses is critical given the need for biomarkers that can be easily measured in clinical settings and used to drive targeted treatment. Further, comprehensively characterising biological reactions to cues promises to aid in the development of therapies that address this specific relapse risk factor. To determine whether brain and cortisol responses to smoking cues are linked, this study recruited 27 nicotine-dependent tobacco-smoking individuals and acquired whole-brain functional activation during a cue reactivity task; salivary cortisol was measured before and after scanning. The results showed that increases in blood-oxygen-level-dependent activation in the right anterior insula and right dorsolateral prefrontal cortex (DLPFC) when viewing smoking versus neutral cues were positively correlated with a post-scan rise in salivary cortisol concentrations. These brain regions have been previously implicated in substance use disorders for their role in salience, interoception and executive processes. These findings show that those who have a rise in cortisol following smoking cue exposure also have a related rise in cue-induced brain reactivity, in brain regions previously linked with heightened relapse vulnerability. This is clinically relevant as measuring cue-induced cortisol responses is a more accessible proxy for assessing the engagement of cue-induced neurobiological processes associated with the maintenance of nicotine dependence.

Psychological and behavioral moderators of physical health among caregivers and non-caregivers.

The current study sought to evaluate whether psychological and/or behavioral health moderate the relationship between caregiving and physical health. MATERIALS AND METHODS: Using data from the Behavioral Risk Factor Surveillance System (BRFSS) survey (2017-2018), separate composite scores were created for psychological and behavioral health. Self-reported physical health was the primary outcome. The sample was 1,387 non-caregivers and 266 caregivers. RESULTS: The psychological, behavioral, and self-reported physical health did not significantly differ between caregivers and non-caregivers, but psychological and behavioral health were shown to differentially affect self-reported health outcomes among caregivers, compared to non-caregivers. Caregivers with worse psychological health had higher odds of experiencing poor physical health versus non-caregivers, while caregivers with better behavioral health had lower odds of having better general health versus non-caregivers. DISCUSSION: These data extend our understanding on how to consider the impact of psychological and behavioral health as a caregiver and opportunities to develop targeted interventions.

The United States National Cancer Institute's Coordinated Research Effort on Tobacco Use as a Major Cause of Morbidity and Mortality among People with HIV.

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease. IMPLICATIONS: This Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population.

Improved clinical outcomes among persons with HIV who quit smoking.

Quitting smoking among people living with HIV/AIDS (PLWHA) is a priority. However, PLWHA and clinicians working with PLWHA are reluctant to use tobacco use treatments out of concern that smoking cessation can diminish anti-retroviral therapy (ART) adherence and quality of life (QoL) and increase psychiatric symptoms. This secondary analysis from a placebo-controlled varenicline trial for tobacco dependence among PLWHA (N = 179) examined if smoking cessation at the end of treatment (EOT) was associated with changes in ART adherence, QoL, anxiety and depression symptoms, and varenicline side effects. ART adherence was not affected by smoking cessation (p > 0.05), remaining ≥98% for all participants. Across 8 QoL subscales, 7 remained unchanged over time across smokers and abstainers; side effects were not associated with cessation. Controlling for baseline smoking rate, adherence to varenicline/placebo and counseling, and treatment arm, participants who had quit smoking at EOT reported a significant reduction in depression (ß = -1.657, 95% CI: -2.893, -0.422, p = .009) and anxiety (ß = -1.434, 95% CI: -2.812, -0.56, p = .041) and increased life satisfaction (ß = 0.88, 95% CI: 0.21, 3.275, p = .027). When PLWHA quit smoking they may not experience adverse clinical outcomes including ART non-adherence and may experience beneficial psychological effects, supporting the use of FDA-approved smoking cessation treatments among PLWHA.

Brain Marker Links Stress and Nicotine Abstinence.

BACKGROUND: Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by reliance on self-reported measures of stress. We utilized a validated functional neuroimaging paradigm to examine whether stress exposure during early abstinence alters objective measures of brain function. METHODS: Seventy-five participants underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during the Montreal Imaging Stress Task (MIST) on two occasions: once during smoking satiety and once following biochemically confirmed 24-hour abstinence (order counterbalanced). The primary outcome measure was brain response during stress (vs. control) blocks of the MIST, assessed using whole-brain analysis corrected for multiple comparisons using clusters determined by Z ≥ 3.1. RESULTS: Abstinence (vs. satiety) was associated with significantly increased activation in the left inferior frontal gyrus, a brain region associated with inhibitory control. Abstinence-induced change in brain response to stress was positively associated with change in self-reported stress. CONCLUSIONS: This study provides objective evidence that the brain response to stress is altered during the first 24 hours of a quit attempt compared to smoking satiety. IMPLICATIONS: These results point to the potential value of inoculating smokers with stress management training prior to a quit attempt.

Neural cue reactivity during acute abstinence predicts short-term smoking relapse.

In smokers, neural responses to smoking cues can be sensitive to acute abstinence, but the degree to which abstinence-related cue reactivity contributes to relapse is not fully understood. This study addressed this question in a sample of 75 smokers who were motivated to quit smoking. Participants underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during presentation of visual smoking cues and neutral stimuli on two occasions: once during smoking satiety and once following 24-hour abstinence (order counterbalanced). Following the imaging sessions, participants received brief smoking cessation counseling prior to a short-term (7-day) quit attempt. The primary smoking cessation outcome was biochemically confirmed 7-day relapse. The secondary smoking cessation outcome measure was total number of self-reported days of abstinence. During abstinence (vs satiety), smoking cue reactivity was significantly increased only in the anterior cingulate cortex (ACC); other regions showing a cue (vs neutral) response did not exhibit an abstinence effect in the stringent whole-brain analysis. Participants who showed greater smoking cue reactivity in the ACC during acute abstinence (compared with smoking satiety) were more likely to relapse (OR = 2.10 per standard deviation increase in percent signal change [abstinence minus smoking satiety], 95% CI: 1.05 to 4.20, P = 0.036). Greater abstinence-induced change in ACC activation also predicted fewer total days abstinent (ß = -0.63, 95% CI = 0.43 to 0.66, P < 0.0001). This study provides the first evidence that changes in smoking cue reactivity in the ACC during acute abstinence predict smoking relapse, thereby improving our understanding of the neurobiology of smoking cessation.

The Role of Cognitive Control in the Self-Regulation and Reinforcement of Smoking Behavior.

Cognitive control (CC)-the ability to regulate attention and memory-plays an important role in a variety of health behaviors, including smoking behavior. In this theoretical review of the literature, we propose a CC and smoking behavior framework that includes (1) the positive influence of CC on the self-regulation of smoking, (2) nicotine-induced improvements in CC that may indirectly reinforce smoking (including withdrawal reversal effects), and (3) the long-term effects of smoking on the brain that may result in reduced CC. Integration of these literatures suggests that CC contributes to both self-regulation (ie, brake pedal) and nicotine-related reinforcement (ie, gas pedal) amid the catastrophic effects of long-term smoking, which may reduce self-regulatory control over smoking while also enhancing indirect reinforcement. Supportive evidence and limitations of this approach will be presented, as well as ideas for future research directions that may fully examine this multifaceted modeling of CC in relation to smoking behavior. IMPLICATIONS: There is substantial evidence that CC contributes to self-regulation (ie, brake pedal) and reinforcement (ie, gas pedal) of smoking behavior as well as evidence that long-term smoking may cause reduced CC. The proposed model delineates how these opposing influences of CC may mask the unique contribution of self-regulation and reinforcement in maintaining smoking behavior. Targeting CC for treating nicotine dependence will require more nuanced approaches that consider the independent and combined effects of self-regulation and reinforcement to improve smoking cessation success rates.

No Effect of Commercial Cognitive Training on Brain Activity, Choice Behavior, or Cognitive Performance.

Increased preference for immediate over delayed rewards and for risky over certain rewards has been associated with unhealthy behavioral choices. Motivated by evidence that enhanced cognitive control can shift choice behavior away from immediate and risky rewards, we tested whether training executive cognitive function could influence choice behavior and brain responses. In this randomized controlled trial, 128 young adults (71 male, 57 female) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. Pretraining and post-training, participants completed cognitive assessments and functional magnetic resonance imaging during performance of the following validated decision-making tasks: delay discounting (choices between smaller rewards now vs larger rewards in the future) and risk sensitivity (choices between larger riskier rewards vs smaller certain rewards). Contrary to our hypothesis, we found no evidence that cognitive training influences neural activity during decision-making; nor did we find effects of cognitive training on measures of delay discounting or risk sensitivity. Participants in the commercial training condition improved with practice on the specific tasks they performed during training, but participants in both conditions showed similar improvement on standardized cognitive measures over time. Moreover, the degree of improvement was comparable to that observed in individuals who were reassessed without any training whatsoever. Commercial adaptive cognitive training appears to have no benefits in healthy young adults above those of standard video games for measures of brain activity, choice behavior, or cognitive performance.SIGNIFICANCE STATEMENT Engagement of neural regions and circuits important in executive cognitive function can bias behavioral choices away from immediate rewards. Activity in these regions may be enhanced through adaptive cognitive training. Commercial brain training programs claim to improve a broad range of mental processes; however, evidence for transfer beyond trained tasks is mixed. We undertook the first randomized controlled trial of the effects of commercial adaptive cognitive training (Lumosity) on neural activity and decision-making in young adults (N = 128) compared with an active control (playing on-line video games). We found no evidence for relative benefits of cognitive training with respect to changes in decision-making behavior or brain response, or for cognitive task performance beyond those specifically trained.

The Intersection of Sex Differences, Tobacco Use, and Inflammation: Implications for Psychiatric Disorders.

PURPOSE OF REVIEW: Tobacco use, sex differences, and psychiatric disorders are associated with altered immune function. There are also sex differences in tobacco use and psychiatric disorders. This review summarizes findings from the small, but growing literature examining sex differences in the effects of tobacco use on inflammation and the implications for psychiatric disorders. RECENT FINDINGS: We identified four studies that tested the interaction between sex and tobacco/nicotine on inflammation. Although males and females generally exhibited differential tobacco-induced immune responses, the pattern varied depending on the sample (rodents vs. humans) and the method to evaluate inflammation. Evidence suggests that sex modulates the effects of tobacco smoke on inflammation. Many inflammation markers associated with sex differences and tobacco use are related to psychiatric disorders. We propose a model in which sex, tobacco use, and inflammation interact to increase risk for psychiatric disorders. Future studies are needed to examine the mechanisms that explain this relationship.

Got chocolate? Bilateral prefrontal cortex stimulation augments chocolate consumption.

BACKGROUND: Understanding the mechanisms behind exerting self-control may reveal why health behaviors are resistant to change. Activity in the right inferior frontal gyrus (rIFG) plays a role in self-control processes and may be modulated using transcranial direct current stimulation (tDCS). OBJECTIVE: In this early phase behavioral research study, we investigated whether anodal stimulation over the rIFG with cathodal stimulation over the left IFG (versus sham) reduced chocolate consumption. METHODS: Twenty-three healthy females (ages 18-35) completed two tDCS sessions (2.0 mA vs. sham; order counterbalanced) in a within-subject, double-blind, randomized design with a 4-week washout. Participants were self-reported "chocolate cravers" and restrained eaters. Self-report assessments on disinhibited eating were completed at intake. Delay discounting and inhibitory control were assessed at the remaining visits. During stimulation, participants completed an inhibitory control training task (chocolate go/no-go task) and were randomized to the chocolate no-go condition (inhibit all responses to chocolate cues) or the control condition (inhibit responses to chocolate cues on half the trials). Following stimulation, participants completed a 15-min chocolate "taste test" with chocolate rating forms. Afterwards, staff measured the remaining chocolate to determine total consumption. RESULTS: Contrary to our hypotheses, active tDCS significantly increased chocolate consumption vs. sham (mean = 43.2 vs. 32.2, p=0.005) in both task conditions, but had no effect on chocolate ratings (ps > 0.05). Higher delay discounting and self-reported disinhibited eating predicted greater consumption (ps < 0.05). CONCLUSIONS: The results suggest widespread activation of the prefrontal cortex may reduce the ability to resist chocolate. Our data highlights important methodological considerations for conducting tDCS studies to target health behaviors.

The nature and consequences of cognitive deficits among tobacco smokers with HIV: a comparison to tobacco smokers without HIV.

HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected (n = 103) and HIV-uninfected smokers (n = 70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p < 0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates "good prediction" for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only (p = 0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population.

Withdrawal-Related Changes in Delay Discounting Predict Short-Term Smoking Abstinence.

INTRODUCTION: Impulsive decision making is associated with smoking behavior and reflects preferences for smaller, immediate rewards and intolerance of temporal delays. Nicotine withdrawal may alter impulsive decision making and time perception. However, little is known about whether withdrawal-related changes in decision making and time perception predict smoking relapse. METHODS: Forty-five smokers (14 female) completed two laboratory sessions, one following 24-hour abstinence and one smoking-as-usual (order counterbalanced; biochemically verified abstinence). During each visit, participants completed measures of time perception, decision making (ie, discount rates), craving, and withdrawal. Following the second laboratory session, subjects underwent a well-validated model of short-term abstinence (quit week) with small monetary incentives for each day of biochemically confirmed abstinence. RESULTS: Smokers significantly overestimated time during abstinence, compared to smoking-as-usual (p = .021), but there were no abstinence effects on discount rates (p = .6). During the quit week, subjects were abstinent for 3.5 days (SD = 2.15) and smoked a total of 12.9 cigarettes (SD = 15.8). Importantly, higher discount rates (ie, preferences for immediate rewards) during abstinence (abstinence minus smoking difference score) predicted greater number of days abstinent (p = .01) and fewer cigarettes smoked during the quit week (p = .02). Withdrawal-related change in time reproduction did not predict relapse (p = .2). CONCLUSIONS: These data suggest that individuals who have a greater preference for immediate rewards during abstinence (vs. smoking-as-usual) may be more successful at maintaining short-term abstinence when provided with frequent (eg, daily) versus less frequent incentive schedules (eg, 1 month). Abstinence-induced changes in decision making may be important for identifying smokers who may benefit from interventions that incentivize abstinence such as contingency management (CM). IMPLICATIONS: The present results suggest that smokers who place greater subjective value on immediate rewards during withdrawal (compared to smoking-as-usual) may be less likely to relapse if offered small, frequent monetary incentives to maintain abstinence. Thus, the current findings may have important implications for identifying smokers most likely to benefit from particular interventions such as CM. Future research might evaluate whether withdrawal-related changes in delay discounting moderate treatment response to different incentive schedules with the goal of optimizing CM effectiveness to improve abstinence rates.

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

BACKGROUND AND OBJECTIVE: Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. METHODS: Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. RESULTS: Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296).

Sex differences in time perception during smoking abstinence.

INTRODUCTION: Nicotine withdrawal leads to impulsive decision-making, which reflects a preference for smaller, immediate rewards and often prompts a relapse to smoking. The mechanism by which nicotine withdrawal leads to impulsive decision-making is not well known. An essential dimension of decision-making is time perception. Impulsive decisions reflect intolerance of temporal delays and the perception that time is passing more slowly. Sex may be an important factor in impulsive decision-making and time perception, but no studies have investigated whether sex moderates the effects of nicotine withdrawal on impulsive decision-making and time perception. METHODS: Thirty-three (12 female) adult smokers completed 2 laboratory sessions: following 24-hr abstinence and once smoking-as-usual (order counterbalanced, abstinence biochemically verified). Participants completed 2 time perception tasks, a decision-making task, and self-report measures of craving, withdrawal, and mood. RESULTS: During time reproduction, males overestimated time during abstinence compared to smoking, whereas there was no session effect for females. On the time discrimination task, smokers were less accurate during abstinence, and this effect tended to be stronger among females. In general, males had higher discounting rates compared with females, but there was no effect of abstinence. CONCLUSIONS: The current data suggest that the effect of abstinence on time perception may be stronger in males and that males generally exhibit steeper delay discounting rates. Time perception may be an important mechanism in smoking abstinence. Our future work will investigate the role of time perception in smoking relapse and whether this is moderated by sex.

Does Extended Pre Quit Bupropion Aid in Extinguishing Smoking Behavior?

INTRODUCTION: Understanding the mechanisms by which bupropion promotes smoking cessation may lead to more effective treatment. To the extent that reduced smoking reinforcement is one such mechanism, a longer duration of pre quit bupropion treatment should promote extinction of smoking behavior. We evaluated whether 4 weeks of pre quit bupropion (extended run-in) results in greater pre quit reductions in smoking rate and cotinine and, secondarily, greater short-term abstinence, than standard 1 week of pre quit bupropion (standard run-in). METHODS: Adult smokers (n = 95; 48 females) were randomized to a standard run-in group (n = 48; 3-week placebo, then 1-week bupropion pre quit) or an extended run-in group (4-week pre quit bupropion; n = 47). Both groups received group behavioral counseling and 7 weeks of post quit bupropion. Smoking rate (and craving, withdrawal, and subjective effects) was collected daily during the pre quit period; biochemical data (cotinine and carbon monoxide) were collected at study visits. RESULTS: During the pre quit period, the extended run-in group exhibited a greater decrease in smoking rate, compared to the standard run-in group, interaction p = .03. Cigarette craving and salivary cotinine followed a similar pattern, though the latter was evident only among women. Biochemically verified 4-week continuous abstinence rates were higher in the extended run-in group (53%) than the standard run-in group (31%), p = .033. CONCLUSIONS: The extended use of bupropion prior to a quit attempt reduces smoking behavior during the pre quit period and improved short-term abstinence rates. The data are consistent with an extinction-of-reinforcement model and support further investigation of extended run-in bupropion therapy for smoking cessation.

Time dependency of craving and response inhibition during nicotine abstinence.

BACKGROUND: Nicotine withdrawal produces increased craving for cigarettes and deficits in response inhibition, and these withdrawal symptoms are predictive of relapse. Although it is well-established that these symptoms emerge early during abstinence, there is mixed evidence regarding whether they occur simultaneously. Given the importance of the early withdrawal period, this study examined craving and response inhibition at 24h and 72h abstinence. METHODS: Twenty-one non-treatment seeking adult smokers were evaluated at baseline, 24h, and 72h abstinence for craving (Questionnaire on Smoking Urges - Brief) and response inhibition (Stop Signal Task, Stroop Task, Continuous Performance Task). Generalized linear regression models were used for primary outcomes, and Pearson correlations for examining the association between craving and response inhibition. RESULTS: Factor 2 craving (anticipated relief of negative affect) increased from baseline to 24h abstinent (p=0.004), which subsided by 72h (p=0.08). Deficits in response inhibition measured by the Stop Signal Task were observed at 72h (p=0.046), but not 24h (p=0.318). No correlation was found between response inhibition and craving at any time point (p-values>0.19), except between the Stroop Task and factor 1 craving at baseline (p=0.025). CONCLUSIONS: Factor 2 craving peaked at 24h, whereas deficits in response inhibition did not emerge until 72h, indicating that need to target craving and cognitive function during early abstinence may not occur simultaneously. Further characterizing the time course of withdrawal symptoms may guide development of targeted treatments for smoking cessation.