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Although the high comorbidity of posttraumatic stress disorder (PTSD) and substance use disorders has been firmly established, no laboratory-based studies have been conducted to examine relationships between the two disorders. Using cue reactivity methodology, this study examined the impact of personalized trauma-image cues and in vivo drug cues on drug-related responding (e.g. craving) in individuals with PTSD and either crack cocaine (CD) or alcohol dependence (AD). CD and AD groups displayed reactivity to both trauma and drug cues when compared to neutral cues, including increased craving. However, the AD group was more reactive than the CD group to both classes of cues. The CD participants were more reactive to trauma-image cues if drug-related material was included in the image while the AD participants were reactive to the trauma cues regardless of drug-related content. It is hypothesized that PTSD-related negative emotion may play a relatively more important role in the maintenance of AD when compared to CD. Evidence that substance dependent individuals with PTSD report increased substance craving in response to trauma memories is offered as a potential contributing factor in the poorer substance abuse treatment outcomes previously documented in this comorbid population. [ABSTRACT FROM AUTHOR]

در این مقاله، تحلیلی از مسئلة اصلی نظریه و رویة قضایی حقوق بشر را بسط می‌دهیم. مشکل به برخورد با هویت دینی در دولت‌هایی مربوط می‌شود که مدعی دفاع از معیارهای حقوق بشر در اروپا هستند. این مشکل - به عنوان مثال - خود را در قالب ممنوعیت اعمال مذهبی خاصی نشان داده است که تصور می‌شود اصول مطابق با مبانی دولت در برخی از حکومت‌های اروپایی را نقض می‌کند. از جملة این اعمال مذهبی می‌توان به پوشیدن روسری و سایر موارد مذهبی توسط کسانی که وظایفی دولتی برعهده دارند (مانند کارمندان دولت و معلمین) یا کسانی که به اماکن عمومی وارد می‌شوند (مانند محصّلان مدارس و دانشگاه‌های دولتی)، اشاره کرد.

Background: Although complex in nature, the pathophysiology of depression involves reduced or impaired neuroplastic capabilities. Restoring or enhancing neuroplasticity may serve as a treatment target for developing therapies for depression. Aerobic exercise (AEx) has antidepressant benefits and may enhance neuroplasticity in depression although the latter has yet to be substantiated. Therefore, we sought to examine the acute effect of AEx on neuroplasticity in depression., Methods: Sixteen individuals with (DEP; 13 female; age = 28.5 ± 7.3; Montgomery-Äsberg Depression Rating Scale [MADRS] = 21.3 ± 5.2) and without depression (HC; 13 female; age 27.2 ± 7.5; MADRS = 0.8 ± 1.2) completed three experimental visits consisting of 15 min of low intensity AEx (LO) at 35% heart rate reserve (HRR), high intensity AEx (HI) at 70% HRR, or sitting (CON). Following AEx, excitatory paired associative stimulation (PAS 25ms ) was employed to probe neuroplasticity. Motor evoked potentials (MEP) were assessed via transcranial magnetic stimulation before and after PAS 25ms to indicate acute changes in neuroplasticity., Results: PAS 25ms primed with HI AEx led to significant increases in MEP amplitude compared to LO and CON. HI AEx elicited enhanced PAS 25ms -induced neuroplasticity for up to 1-h post-PAS. There were no significant between-group differences., Conclusion: HI AEx enhances PAS measured neuroplasticity in individuals with and without depression. HI AEx may have a potent influence on the brain and serve as an effective primer, or adjunct, to therapies that seek to harness neuroplasticity., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

Introduction: Females, versus males, have shown a slower decline in smoking prevalence, greater smoking-related mortality and morbidity, and tend to have more difficulty achieving and maintaining abstinence. Identifying sex-specific risk factors is needed to improve outcomes. Though ovarian hormones have been evaluated for their role in smoking and relapse, measures tend to be static and infrequent, failing to capture the influence of increasing or decreasing levels., Aims and Methods: The present study evaluated the effect of static and fluctuating levels of ovarian hormones (ie, progesterone, estradiol, and estrogen to progesterone [E/P] ratio) on stress reactivity, cigarette craving, and smoking during a laboratory relapse paradigm. Female participants (assigned female at birth) reporting daily cigarette smoking (N = 91, ages 18-45) were recruited from the community. Participants provided daily salivary ovarian hormone levels leading up to a laboratory session, in which stress was induced and stress reactivity, cigarette craving, latency to smoke, and ad-libitum smoking were measured., Results: Static levels of estradiol were associated with stress reactivity (β = 0.28, SE = 0.13) and static E/P ratio was associated with smoking in the laboratory (HR = 1.4). Preceding 3-day changes in estradiol and E/P ratio, but neither static levels nor preceding 3-day changes in progesterone were associated with stress reactivity, cigarette craving, or smoking in a relapse paradigm., Conclusions: Ovarian hormones are among several sex-specific factors involved in the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood., Implications: Findings of the present study provide novel information regarding the role of ovarian hormones among female participants who smoke daily in stress reactivity and smoking in the context of a laboratory relapse paradigm and highlight several avenues for future research. We found that same-day estradiol levels were associated with increased subjective stress reactivity and same-day estrogen to progesterone ratio was associated with increased likelihood of smoking in a relapse paradigm. Ovarian hormones are among several sex-specific factors contributing to the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite decades of progress, cigarette smoking remains a significant contributor to disease burden. This effect is especially pronounced for specific priority populations, such as individuals who live in rural communities, in that the burden of tobacco smoking is greater among these groups than in urban areas and the general population. The present study aims to evaluate the feasibility and acceptability of two novel tobacco treatment interventions delivered through remote telehealth procedures to individuals who smoke in the state of South Carolina. Results also include exploratory analyses of smoking cessation outcomes. Study I evaluated savoring, a strategy based on mindfulness practices, alongside nicotine replacement therapy (NRT). Study II evaluated retrieval-extinction training (RET), a memory-modification paradigm alongside NRT. In Study I (savoring), recruitment and retention data showed high interest and engagement in the intervention components, and participants who received this intervention decreased cigarette smoking throughout the course of the treatment ( p s < .05). In Study II (RET), results showed high interest and moderate engagement in treatment, although exploratory outcome analyses did not demonstrate significant treatment effects on smoking behaviors. Overall, both studies showed promise in generating interest among individuals who smoke in participating in remotely delivered, telehealth smoking cessation interventions with novel therapeutic targets. A brief savoring intervention appeared to have effects on cigarette smoking throughout treatment, whereas RET did not. Gaining insight from the present pilot study, future studies may improve the efficacy of these procedures and incorporate the treatment components into more robust available treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Two primary ovarian hormones that fluctuate across the female menstrual cycle-estradiol and progesterone-have been independently linked in separate literatures to nicotine reinforcement and anxiety psychopathology. We identify existing methodological limitations in these literatures, describe an example protocol that was developed to address such limitations, highlight case examples, and offer insights on the resulting advantages and challenges. This protocol was an observational, prospective, within-subjects study of female cigarette smokers who were followed over the course of a complete menstrual cycle. Non-treatment seeking, female cigarette smokers ( N  = 50), between the ages of 18-40 who have a normal menstrual cycle (25-35 days in length) were recruited from the community. Females with anxiety or mood psychopathology represented 38.0% of the sample. Salivary progesterone and estradiol were assessed each morning via at-home saliva collection methods. Self-reported within-day momentary ratings of anxiety and nicotine reinforcement were collected using ecological momentary assessment (EMA) via a mobile app. Protocol compliance was >85%. Within- and between-subjects heterogeneity was observed in the progesterone and estradiol, anxiety, and nicotine craving measures, especially in the context of anxiety psychopathology. We aimed to integrate the anxiety and nicotine dependence literatures and advance the empirical study of the role of ovarian hormones. This protocol reflects an intensive, yet feasible approach to collecting daily-level naturalistic data related to estradiol, progesterone, anxiety, and nicotine reinforcement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Farris, Smith, Steinberg, Altman, Lambert-Messerlian, Dunsiger, Williams, Saladin and Abrantes.)

Objective: Cannabis use motives and craving are associated with increased risk for cannabis-related problems and are ideal targets for prevention and early intervention. Patterns of motives and craving reactivity to cannabis cues differ by sex; however, few studies closely examine the relationship between motives and craving and how it may differ by valence (±) across men and women., Method: The present study used Cue Reactivity Ecological Momentary Assessment to assess reward (+) and relief (-) craving four semirandom times per day for 2 weeks in a sample of 63 emerging adults (age 18-21; 54% cisgender women; 85.7% White) who frequently use cannabis (≥ 3 times per week). We assessed craving before and after exposure to brief neutral or cannabis image cues and examined within- and between-participant effects of cue type, motives, sex/gender, and their interactions, on postcue cannabis craving., Results: Regardless of cue type, women with high coping motives (-) reported less postcue relief (-) craving, and men with high enhancement motives (+) reported more postcue reward (+) craving. High enhancement motives (+), regardless of sex/gender, were associated with elevated relief (-) craving reactivity to cannabis cues, and women with high coping motives (-) reported elevated reward (+) craving reactivity to cannabis cues., Conclusions: Sex/gender differences in the relationships between cannabis motives and craving reactivity indicate the value of a more targeted examination of valence (±) of craving experiences in addition to motives for use. Higher levels of precision may better inform interventions for emerging adults at risk for experiencing cannabis-related problems. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders (SUDs) and engagement in risky substance use behaviors. Women are overrepresented among individuals with more severe childhood adversity (≥4 types of ACEs) and may be at particular risk for aberrant substance use. Objectives: To assess the prevalence of ACEs among men and women with cannabis, opioid, cocaine, and tobacco use disorders. Methods: Non-treatment-seeking individuals participating in clinical addiction research at a single site completed the ACE questionnaire and provided a detailed substance use history. Data were analyzed using proportional odds models and logistic regression. Results: Most participants (424/565; 75%) reported at least one ACE, and more than one-quarter (156/565; 27%) reported severe childhood adversity. Relative to men ( n  = 283), women ( n  = 282) reported more ACEs (OR = 1.49; p  = .01) and more experiences of emotional/physical abuse (OR = 1.52; p  = .02), sexual abuse (OR = 4.08; p  = .04), and neglect (OR = 2.30; p  < .01). Participants in the cocaine (OR = 1.87; n = .01) and opioid (OR = 2.21; p  = .01) use disorder, but not cannabis use disorder (OR = 1.46; p  = .08), studies reported more severe adversity relative to the tobacco group. Relative to tobacco users, emotional/physical abuse (OR = 1.92; p  = .02) and neglect (OR = 2.46; p  = .01) scores were higher in cocaine users and household dysfunction scores were higher in opioid users (OR = 2.67; p  = .01). Conclusion: The prevalence of ACEs differs with respect to both participant gender and primary substance used. Novel SUD treatment strategies that incorporate ACEs may be uniquely beneficial in specific subpopulations of people with SUDs.

The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common following sexual assault and associated with more severe symptomology and increased likelihood of sexual revictimization. Integrated interventions aimed at reducing PTSD and AUD symptoms following recent sexual assault are needed and should address barriers to care and early treatment termination. The proposed study will test a novel, brief (5 to 7 sessions) intervention that integrates Written Exposure Therapy for PTSD and Cognitive Behavioral Therapy for AUD, and is initiated within the first six weeks post-assault. In Phase 1, qualitative analysis of content gathered during focus groups with treatment providers will be conducted to inform intervention development. In Phase 2, a proof-of-concept pilot study (n = 10) of the intervention, Substance Use Skills Training and Exposure Post-Sexual Assault (STEPS), will be conducted. In Phase 3, a pilot randomized controlled trial (RCT) among 54 recent sexual assault survivors will be implemented using the updated manualized STEPS intervention to evaluate feasibility and preliminary efficacy in reducing PTSD and AUD symptoms. Ecological momentary assessments will be used to assess daily alcohol use, craving, affect, intrusions and avoidance. The effects of STEPS on commonly associated symptoms (e.g., depression, substance use) will be examined. The proposed study has the potential to make a significant public health impact by advancing knowledge on the link between sexual assault and co-occurring PTSD and AUD and informing early intervention efforts for this high-risk population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Brian Marx receives royalties from the American Psychological Association for publishing the Written Exposure Therapy manual., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Globally, depression is a leading cause of disability and has remained so for decades. Antidepressant medications have suboptimal outcomes and are too frequently associated with side effects, highlighting the need for alternative treatment options. Although primarily known for its robust physical health benefits, exercise is increasingly recognized for its mental health and antidepressant benefits. Empirical evidence indicates that exercise is effective in treating individuals with depression; however, the mechanisms by which exercise exerts anti-depressant effects are not fully understood. Acute bouts of exercise have been shown to transiently modulate circulating levels of serotonin and norepinephrine, brain-derived neurotrophic factor, and a variety of immuno-inflammatory mechanisms in clinical cohorts with depression. However, exercise training has not been demonstrated to consistently modulate such mechanisms, and evidence linking these putative mechanisms and reductions in depression is lacking. The complexity of the biological underpinnings of depression coupled with the intricate molecular cascade induced by exercise are significant obstacles in the attempt to disentangle exercise's effects on depression. Notwithstanding our limited understanding of these effects, clinical evidence uniformly argues for the use of exercise to treat depression. Regrettably, exercise remains underutilized despite being an accessible, low-cost alternative/adjunctive intervention that can simultaneously reduce depression and improve overall health. To address the gaps in our understanding of the clinical and molecular effects of exercise on depression, we propose a model that leverages systems biology and multidisciplinary team science with a large-scale public health investment. Until the science matches the scale of complexity and burden posed by depression, our ability to advance knowledge and treatment will continue to be plagued by fragmented, irreproducible mechanistic findings and no guidelines for standards of care., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Fluctuations in ovarian hormones have been associated with changes in cigarette smoking behavior, which can be measured through both serum or less invasive salivary procedures. The primary aim of this exploratory study is to characterize the progesterone profiles of salivary progesterone measurements and to compare that with the profiles estimated from a previously measured serum sample., Aims and Methods: Nontreatment-seeking, cigarette smoking women (n = 82; ages 18-45 years) provided daily salivary hormone samples every morning for 14 consecutive days. Time-dependent random effects functions were used to approximate daily salivary progesterone (ng/mL) levels over the course of a standardized menstrual cycle. Serum measures of progesterone from a previous study of female cigarette smokers were examined for consistency with established profiles and compared with the salivary profile using the same methodology., Results: The salivary model fit exhibits relative stability during the follicular phase and a clear unimodal peak during the luteal phase. Parameter estimates from the non-linear function show correspondence to serum data. Although the profiles estimated from salivary and serum data agree in functional form, we observed larger between-subject heterogeneity both in the follicular level and the peak luteal level in salivary measures., Conclusions: The pattern of salivary and serum progesterone measured across the menstrual cycle is similar in form, which is noteworthy given that the saliva and serum samples were drawn from independent sample of female smokers. Inter- and intra-individual variation in salivary measures may be greater than in serum measures., Implications: Measuring progesterone level variation across the menstrual cycle via saliva samples has several benefits relative to serum sampling methods in that they are easily obtained, noninvasive, and low-cost. Inter- and intra-individual variation in measurements may be greater than those in serum measurements. However, the functional form of the salivary progesterone profile is isomorphic to serum progesterone., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Distress tolerance (DT) has been implicated as an important factor in the experience of negative affect (NA) and cannabis craving. However, previous research is limited by its use of laboratory paradigms that may not replicate in naturalistic settings. The current study examined how DT influenced reactivity to NA cues in daily life in a sample of frequent (≥3 times per week) cannabis-using emerging adults (age 18-21)., Methods: Using cue-reactivity ecological momentary assessment (CREMA), 63 (54 % female; 85.7 % white; M age = 19.62) participants reported on their cannabis craving and affect (sadness, relaxation) four semi-random times per day for two weeks (56 possible CREMA sessions/participant). We assessed affect and cannabis craving before and after exposure to neutral and NA cues. Multilevel modeling was used to examine within- and between-participant effects of cues, DT, and sex, as well as within- and between-participant average pre-cue affect and craving, on post-cue affect and craving., Results: NA cues consistently predicted higher-than-normal post-cue sadness and lower relaxation, but not greater-than-normal post-cue craving. Cue type interacted with sex and DT to predict post-cue sadness, but not craving. Female participants and those reporting low DT reported higher sadness following NA cues compared to males and those with high DT, respectively., Conclusions: Frequent cannabis-using emerging adults differed in affect, but not cannabis craving, reactivity to NA cues as a function of sex and DT. Our results were partially consistent with prior human laboratory and CREMA research finding greater reactivity to NA cues among females and individuals with low DT., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Rationale: The hypothalamic-pituitary-adrenal (HPA) axis is a critical hormonal system involved in stress response. A number of studies have investigated the HPA axis response of drug-dependent individuals to stressors. Stress-induced vulnerabilities in the HPA axis may differ in response to chronic use of different substances, possibly leading to different target therapies. There has not been a direct comparison of HPA axis and subjective response between individuals with different types of substance use disorders following a laboratory stress intervention., Objectives: The primary goal of the current study was to compare subjective and neuroendocrine response to the Trier Social Stress Task (TSST) across multiple primary types of substance use disorders and investigate differential response between males and females., Methods: Four hundred participants were drawn from seven studies completed at the Medical University of South Carolina between 2011 and 2021. The TSST was utilized across studies and subjective and neuroendocrine responses measured following completion. Generalized linear mixed effects models and area under the response curve analysis were used to compare both substance type and sex differences., Results: The study groups involving individuals with cocaine use disorder had blunted stress, craving and cortisol response following the TSST as compared to other substance use groups. Females in the cocaine groups reported higher subjective stress but lower cortisol than males., Conclusions: The study results indicate that there may be differential effects of substances on the HPA axis, with cocaine using individuals exhibiting more blunting of the HPA axis response as compared to users of other substances., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Medication sampling is a clinically useful tool to engage smokers in the quitting process. Whether varenicline is suitable for sampling purposes is unclear. The purpose of this study was to examine the feasibility, uptake, and preliminary outcomes of varenicline sampling., Methods: Smokers (N = 99), both motivated to quit and not, were recruited and randomized to varenicline sampling versus not, with 12 week follow-up. The intervention consisted of mailing one-time samples of varenicline (lasting 2-4 wks), with minimally suggestive guidance on use., Results: Uptake of varenicline was strong, at 2 weeks (54% any use, 66% daily use) and 4 weeks (38%, 46%), with 58% of medication users seeking additional medication. Most users followed conventional titration patterns, self-titrating from 0.5 mg to 2 mg. Relative to control, varenicline sampling increased motivation (p = 0.006) and confidence to quit (p = 0.02), and decreased cigarette smoking (p = 0.02). Smokers receiving varenicline samples were significantly more likely to achieve 50% reduction in cigarettes per day (CPD), both immediately following the sampling exercise (Adjusted Odds Ratio [AOR] = 4.12; 95% CI: 1.39 to 12.17) and at final follow-up (AOR = 4.50; 95% CI: 1.56 to 13.01). Though cessation outcomes were not statistically significant, there was a 1.5 to 3-fold increase in quit attempts and abstinence from varenicline sampling throughout follow-up. These outcomes were comparable among smokers motivated to quit and not., Conclusions: Unguided, user-driven sampling of varenicline sampling is a concrete behavioral exercise that is feasible to do and seems to suggest clinical utility. Sampling is a pragmatic clinical approach to engage more smokers in quitting., Implications: Use of evidence-based pharmacotherapies for smoking cessation is low. Medication sampling is a pragmatic behavioral exercise that allows smokers to experience the benefits of using them, while promoting positive downstream effects towards quitting. While previous studies have shown that nicotine replacement therapy (NRT) sampling is viable and effective, whether this extends to varenicline is unclear. Results from this trial demonstrate that varenicline sampling is feasible, safe, and suggestive of clinically important steps toward quitting, deserving of a larger trial., Clinical Trial Registration: NCT #03742154., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Despite advances in prevention and treatment, cigarette smoking remains a leading cause of preventable death in the United States. Although men and women are equally likely to attempt to quit smoking cigarettes, women are far less likely to achieve abstinence both during and following cessation treatment. Recent evidence suggests that ovarian hormone levels may play a role in successful abstinence attempts in women smokers. The primary goal of this exploratory prospective observational study was to estimate the association between within-participant levels of progesterone and estradiol with associated cigarettes smoked per day in adult women smokers (n = 104). The primary study outcome was self-reported cigarettes smoked per day (CPD) during a 2-week observational period collected using a daily smoking diary. Additionally, participants collected saliva daily, from which hormone levels (progesterone and estradiol) were derived. Higher within-participant progesterone levels were associated with a significant decrease in CPD (p = .008) whereas within-participant estradiol levels were unrelated to CPD (p = .25). Regression models indicated a single change in the trajectory of smoking behavior for both within-participant progesterone and estradiol. When progesterone values were below the change point, there was a significant inverse relationship between within-participant progesterone levels and smoking behavior (p = .025) whereas the relationship was attenuated for higher within-participant progesterone levels (p = .59). The effect of estradiol on smoking behavior was not significant when it was either below (p = .92) or above (p = .16) the change point. Higher within-participant levels of progesterone but not estradiol are associated with reduced CPD in nontreatment seeking women smokers., (© 2020 Society for the Study of Addiction.)

Adverse childhood experiences (ACE) are associated with greater neuroendocrine responses to social stress in substance users. The neuropeptide oxytocin might attenuate this relationship. Given sex differences in ACE exposure and neuroendocrine stress reactivity, it is unknown whether this association is similar for males and females. Therefore, this secondary analysis evaluated the interactive effect of sex, ACE, and acute oxytocin administration on neuroendocrine stress responses in adult cigarette smokers (N = 144). Participants completed the Adverse Childhood Experiences Questionnaire at screening and were randomized to receive intranasal oxytocin or placebo before undergoing the Trier Social Stress Task (TSST). Cortisol levels were assessed at pre- and post-medication administration and at 20 and 40 min following the TSST. Generalized linear mixed models were developed to predict post-TSST cortisol levels. Predictors included treatment assignment (placebo vs. oxytocin), sex (male vs. female), ACE (0-10 total score), pre-medication cortisol levels, and minutes since medication administration. The hypothesized three-way interaction between sex, oxytocin, and ACE scores was significant. Linear associations between ACE scores and cortisol reactivity indicated higher ACE scores were associated with attenuated cortisol response in females, regardless of treatment condition. For males, higher ACE scores were associated with heightened cortisol response, an effect that was attenuated by oxytocin. Results indicate that the association between ACE and neuroendocrine reactivity to social stress, as well as the attenuating effect of oxytocin, is differentially impacted by sex. Males with greater childhood adversity may be more likely to benefit from oxytocin's anxiolytic properties., (Copyright © 2020. Published by Elsevier Ltd.)

Rationale: Female cigarette smokers tend to show greater cessation failure compared with males. Variables that contribute to the maintenance of smoking, including stress and craving, may differentially impact male and female smokers. Novel pharmacotherapies, such as oxytocin, may attenuate stress reactivity and craving in smokers, but work in this area is limited., Objectives: This study assessed the influence of gender and oxytocin on stress reactivity, craving, and smoking in a randomized, placebo-controlled laboratory relapse paradigm., Methods: Male and female adult cigarette smokers (ages 18-45) were enrolled (women oversampled 2:1) and completed a laboratory session, in which intranasal oxytocin or placebo was administered followed by a laboratory social stress task. The role of gender and oxytocin were assessed on measures of stress reactivity, cigarette craving, latency to smoke in a resistance task, subjective responses to smoking, and ad-libitum smoking., Results: Participants (N = 144) had a mean age of 31 were 63% female and 56% White. Following stress induction, female smokers evidenced greater subjective stress than males, though males demonstrated greater neuroendocrine reactivity and smoking intensity than females. No gender differences were demonstrated for craving. Oxytocin did not attenuate any aspect of stress reactivity, craving, smoking, or subjective responses to smoking compared with placebo., Conclusions: Gender differences in stress reactivity were shown in the hypothesized direction, but oxytocin appeared to exert little impact on subjective or behavioral metrics. Results highlight the complex relationship between gender, stress, and smoking, as well as the implications for oxytocin as a potential pharmacotherapy for smoking cessation.

Introduction: Some evidence suggests that female smokers may show more context-dependent smoking and that males may show more stereotyped smoking (regardless of stress or cue exposure). The goal of this study was to characterize sex differences in response to stressful and smoking cues ecologically presented in daily life and variability in day-to-day smoking behavior., Methods: Adult smokers (N = 177) provided ratings of mood and cigarette craving before and after stress and smoking cues were presented four times daily for 14 days via a mobile device. Linear mixed models tested whether (1) female smokers exhibited greater reactivity to stressful cues than male smokers; (2) pre-cue negative affect increased reactivity to smoking cues more in female smokers than male smokers; (3) across both sexes, greater reactivity to stressful and smoking cues correlated with greater quantity of smoking within a day; and (4) female smokers exhibited greater variability in cigarettes per day (CPD) relative to males., Results: Relative to male smokers, female smokers reported greater negative affect, stress, and craving in response to stressful cues, but not smoking cues, after accounting for time since last cigarette and pre-cue responding. No sex differences in CPD or variability in CPD were detected. Days with higher subjective reactivity to cues were not associated with increased smoking, in either males or females., Conclusions: Sex differences were observed in response to stress but not smoking cues in the natural environment of regular cigarette smokers. Further research is necessary to evaluate whether stress reactivity in female smokers is associated with reduced latency to smoke following stress exposure in daily life., Implications: This study provides naturalistic evidence that female smokers may not be more reactive to smoking cues than males, but experience heightened stress and craving following stress exposure. There was no evidence to support the hypothesis that amount smoked per day varied more for females, relative to males, as a result of more context-driven smoking for females., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Cigarette smoking is the leading cause of preventable morbidity and mortality in the United States and worldwide, and most tobacco users begin smoking in adolescence. Although advances have yielded efficacious pharmacotherapies to complement smoking cessation counseling in adults, far less progress has been made in addressing tobacco use in adolescence., Objective: To evaluate the efficacy and safety of varenicline tartrate for smoking cessation in adolescents and young adults., Design, Setting, and Participants: This 2-group randomized, placebo-controlled, double-blind intention-to-treat clinical trial enrolled a volunteer sample of treatment-seeking adolescent and young adult cigarette smokers (n = 157) aged 14 to 21 years at an outpatient clinical site in Charleston, South Carolina, from August 15, 2012, to October 20, 2017. Follow-up was completed on January 25, 2018. Data were analyzed from March 19, 2018, to August 11, 2018, with further revisions completed April 10, 2019., Interventions: Participants were randomized in a 1:1 ratio to a 12-week course of varenicline (n = 77) or placebo (n = 80). All participants received weekly smoking cessation counseling., Main Outcomes and Measures: The preselected primary efficacy outcome was urine cotinine level-confirmed 7-day abstinence at the end of treatment. Secondary efficacy outcomes included weekly abstinence throughout active treatment, abstinence at posttreatment follow-up visits, and time to first 7-day abstinence. The primary safety outcome was the frequency of treatment-emergent adverse events., Results: A total of 157 participants were enrolled (94 male [59.9%]; mean [SD] age, 19.1 [1.5] years). The varenicline and placebo groups did not differ in the primary outcome of cotinine-confirmed self-reported 7-day abstinence at the end of treatment (varenicline group, 4 of 45 [8.9%]; placebo group, 4 of 45 [8.9%]; risk ratio [RR], 0.97; 95% CI, 0.29-2.99; P = .96). However, among secondary outcomes, the varenicline group achieved self-reported earlier abstinence of at least 7 days (hazard ratio, 1.91; 95% CI, 1.12-3.27) and demonstrated higher rates of self-reported weekly abstinence during the full course of treatment (RR, 1.81; 95% CI, 1.09-2.99; P = .02) and at posttreatment follow-up (RR, 1.82; 95% CI, 1.01-3.28; P = .02). Study medication was generally well tolerated, and treatment-emergent adverse events did not differ between groups (any adverse events, 55 [71.4%] in the varenicline group vs 60 [75.0%] in the placebo group; RR, 0.95; 95% CI, 0.79-1.15; P = .61)., Conclusions and Relevance: When added to weekly cessation counseling for adolescent cigarette smokers, varenicline, compared with placebo, was well tolerated but did not improve end-of-treatment abstinence. However, varenicline may hasten abstinence and yield improvements in posttreatment abstinence outcomes., Trial Registration: ClinicalTrials.gov identifier: NCT01509547.

Memories are often conceptualized as permanent entities; however, retrieval of memories via stimulus prompts can return them to an active state, which initiates a period of lability before the memories are reconsolidated into long-term storage. Importantly, during this period, memories can be disrupted/altered. A growing body of work has focused on translating animal and experimental science into reconsolidation-based interventions for clinical disorders maintained by maladaptive memories. Interventions targeting reward-based and fear-based memories undergirding substance use and anxiety-related disorders, respectively, have shown significant potential. There are several promising pharmacological agents and behavioral approaches that have been used to therapeutically target memory reconsolidation. Here, we discuss the current state of science with special emphasis on the clinical utility of these approaches., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Understanding variability in smoking patterns may inform smoking cessation interventions. Retrospective reports of cigarettes smoked per day may be biased and typically do not provide temporal precision regarding when cigarettes are smoked. However, real-time, user-initiated tracking, such as logging each time a cigarette is smoked, can be burdensome over long time frames. In this study, adult, non-treatment seeking daily smokers (N = 22) used an electronic, smart lighter to light and timestamp cigarettes for 14 days. Participants reported number of cigarettes smoked per day (CPD) via a mobile device (daily diary) and retrospectively reported CPD at the end of the study using the Timeline Followback (TLFB). Self-reported lighter satisfaction and adherence varied with 68% of participants reporting that they liked using the lighter and participants reporting using the lighter for 92% of cigarettes smoked, on average. Lighter-estimated CPD did not differ from daily diary-estimated CPD, but was significantly lower than TLFB estimates. The lighter resulted in greater day-to-day variability relative to other methods and fewer rounded cigarette counts (digit bias) relative to the TLFB. The lighter appears to be feasible for capturing data on smoking patterns in daily smokers. Though false positive cigarettes are likely low, additional technologies that augment data captured from the lighter may be necessary to reduce false negatives (missed cigarettes) and alternative lighter designs may appeal more to certain smokers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aerobic exercise (AEx) exerts antidepressant effects, although the neurobiological mechanisms underlying such effects are not well understood. Reduced brain-derived neurotrophic factor (BDNF) and elevated cortisol have been implicated in the pathophysiology of depression and appear to normalize with antidepressant treatment. Thus, BDNF and cortisol may serve as biological targets for developing AEx as an antidepressant treatment., Purpose: This study examined the effects of AEx, of different intensities, on serum BDNF and cortisol in individuals with and without depression., Methods: Thirteen participants with depression (10 females; age = 27.2 ± 6.9 yr; Montgomery-Äsberg Depression Rating Scale = 21.7 ± 4.7) and 13 control participants (10 females; age 27.2 ± 7.2 yr; Montgomery-Äsberg Depression Rating Scale = 0.5 ± 0.9) participated. Experimental visits consisted of 15 min of low-intensity cycling (LO) at 35% heart rate reserve, high-intensity cycling (HI) at 70% heart rate reserve, or sitting (CON). During each visit, blood samples were obtained at baseline, immediately postexercise (IP), and then every 15 min postexercise for 1 h (15P, 30P, 45P, and 60P). Group, condition, and time differences in BDNF and cortisol were assessed., Results: There were no group differences in cortisol and BDNF. Secondary analysis revealed that BDNF increased in an intensity-dependent nature at IP, and cortisol was significantly elevated at 15P after HI. Changes in BDNF and cortisol showed significant linear relationships with changes in HR., Conclusion: HI AEx can elicit acute, transient increases in BDNF and cortisol in young, healthy, and physically active, nondepressed and mild to moderately depressed individuals. This work suggests that AEx has potential to significantly affect the central nervous system function, and the magnitude of such effect may be directly driven by exercise intensity.

Although distress tolerance (DT) is associated with smoking lapse and relapse outcomes, few studies have conducted a rigorous assessment of DT across domain and method in the context of acute abstinence. In a human laboratory-based study of 106 adult daily smokers, we examined between multiple indices of DT and smoking lapse, withdrawal processes, and motivation to quit. We expected that low DT would be associated with shorter latency to smoke, greater withdrawal severity, and lower motivation to quit. Following a smoking abstinence period (≥ 6 hr deprived), participants completed an assessment battery including both behavioral (mirror-tracing, serial addition, cold pressor, and breath-holding tasks) and self-report measures of DT (general and smoking-specific), withdrawal processes (craving, negative affect, and positive affect), and motivation to quit. Latency to smoke (range = 0-50 min) was assessed in a laboratory analogue task in which delaying smoking was monetarily rewarded. Behavioral and self-report DT indices displayed only modest intercorrelations, indicating different facets of this construct by domain and method of assessment. Tolerance of physical pain was uniquely associated with smoking choice. Both self-report DT measures were associated with abstinence-induced increases in negative affect, while only smoking-specific DT was positively associated with craving. Results are discussed within the context of guiding targeted behavioral interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: Long-term abstinence can be undermined by cessation fatigue-an exhaustion of coping resources attributable to quitting smoking/staying quit. The current study examines the predictive validity of a Cessation Fatigue Scale (CFS; three subscales). Among current smokers, we hypothesized higher fatigue would predict longer latency to both quit initiation and achieving 7-day point prevalence abstinence (7-day PPA). Among recent quitters, we expected higher cessation fatigue would confer greater lapse/relapse risk. Lower rates of abstinence at 2-month follow-up were expected for those with higher fatigue., Method: Current smokers motivated to quit in the next month (n = 301) and recent quitters (n = 242) were assessed biweekly over the course of 2 months. Retention rates were high (>85%). Cox and logistic regression analyses tested hypotheses., Results: Among smokers, greater emotional exhaustion predicted longer delay to achieving 7-day PPA (HR = .53, 95% CI [.40, -.68], p < .001) and lower likelihood of 7-day PPA at 2-month follow-up (OR = .27, 95% CI [.16, -.46], p < .001), even after controlling for nicotine dependence and motivation to quit. Among recent quitters, emotional exhaustion progressively increased over the first 6 weeks since quit initiation. Elevated exhaustion was associated with greater lapse (HR = 1.65, 95% CI [1.06, 2.56], p < .05) and relapse (HR = 2.33, 95% CI [1.37, 3.97], p < .01) risk, and lower likelihood of 7-day PPA at 2-month follow-up (OR = .39, 95% CI [.16, .94], p < .05), even after controlling for nicotine withdrawal and motivation to quit., Conclusions: Cessation fatigue, as measured by the CFS's emotional exhaustion subscale, prospectively predicted important cessation milestones. Findings suggest that cessation fatigue is a novel process that undermines smoking cessation and a viable target for intervention. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Introduction: The Intolerance for Smoking Abstinence Discomfort Questionnaire (IDQ-S) assesses distress tolerance specific to nicotine withdrawal. Though developed to assess withdrawal-related distress, the IDQ-S has not been validated among nicotine-deprived, treatment-seeking smokers. The present study extended previous research by examining the predictive utility of the IDQ-S among abstinent, motivated-to-quit smokers., Methods: Abstinent, treatment-seeking smokers completed the IDQ-S Withdrawal Intolerance and Lack of Cognitive Coping scales, assessments of nicotine dependence and reinforcement, and smoking history at baseline. At baseline and at 24-h, 2-week, and 1-month follow-up, participants completed a smoking cue-reactivity task (collection of cue-elicited craving and negative affect), and assessments of cigarettes per day (CPD; daily diaries at follow-up), carbon monoxide (CO), and cotinine., Results: Greater IDQ-S Withdrawal Intolerance was associated with younger age, higher nicotine dependence and reinforcement, and less smoking years (ps < .03). Greater IDQ-S Lack of Cognitive Coping was associated with less education, lower nicotine dependence and reinforcement, higher baseline CPD, and no prior quit attempts (ps < .04). IDQ-S scales did not significantly predict cue-elicited craving or negative affect, CPD, CO, or cotinine levels at follow-up (ps > .10)., Conclusions: Withdrawal intolerance and lack of cognitive coping did not predict smoking outcomes among nicotine-deprived, treatment-seeking smokers, but were associated with smoking characteristics, including nicotine dependence and reinforcement. Withdrawal intolerance and lack of cognitive coping may not be especially useful in predicting craving and smoking behavior, but future studies should replicate the present study's findings and assess the stability of the IDQ-S before forming firm conclusions about its predictive utility., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This represents a potentially transformative strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, modulation of naturalistic maladaptive memories may be limited by 'boundary conditions' imposed on the reconsolidation process by the nature of these memories., Methods: We conducted a systematic review and meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward- and threat-related memories in (sub) clinical substance use and anxiety/trauma, respectively., Results: Of 4938 publications assessed for eligibility, 8 studies of substance use and 10 of anxiety (phobia)- and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with most studies favouring the 'retrieval + treatment' condition. However, the magnitude of effects was dependent upon the nature of treatment, with pharmacological interventions showing a medium-sized effect (g = 0.59, p = 0.03) and behavioural treatments, a relatively small effect (g = 0.32, p = 0.10) in studies of phobia/trauma. Among studies of substance use, post-retrieval behavioural interventions yielded a larger effect (g = 0.60, p < 0.001) relative to pharmacological treatments (g = - 0.03, p = 0.91), with treatment type being a statistically significant moderator (χ 2 (1) = 4.20, p = 0.04)., Conclusion: Modification of naturalistic maladaptive memories during reconsolidation appears to be a viable treatment strategy for substance use and phobias/trauma disorders. However, high levels of heterogeneity and methodological variation limit the strength of conclusions that can be drawn from the reviewed studies at this stage.

Importance: Recent research on addiction-related memory processes suggests that protracted extinction training following brief cue-elicited memory retrieval (ie, retrieval-extinction [R-E] training) can attenuate/eradicate the ability of cues to elicit learned behaviors. One study reported that cue-elicited craving among detoxified heroin addicts was substantially attenuated following R-E training and through 6-month follow-up., Objective: To build on these impressive findings by examining whether R-E training could attenuate smoking-related craving and behavior., Design, Setting, and Participants: This prospective, mixed-design, human laboratory randomized clinical trial took place between December 2013 and September 2015. Participants were recruited in Charleston, South Carolina. Study sessions took place at the Medical University of South Carolina. The participants were 168 screened volunteer smokers, of whom 88 were randomized; 72 of these 88 participants (81.8%) attended all the follow-up sessions through 1 month. The primary eligibility criteria were current nicotine dependence (DSM criteria), smoking 10 or more cigarettes per day, and a willingness to attempt smoking cessation., Interventions: Participants were randomly assigned to receive either smoking-related memory retrieval followed by extinction training (the R-E group) or nonsmoking-related retrieval followed by extinction training (the NR-E group)., Main Outcomes and Measures: Primary outcomes were cue-elicited craving and physiological responding to familiar and novel cues in the R-E group vs the NR-E group over a 1-month follow-up period. Secondary outcomes were smoking-related behaviors., Results: A total of 44 participants were randomly assigned to the R-E group (mean age, 48.3 years; 72.7% male); a total of 44 participants were randomly assigned to the NR-E group, with 43 attending at least 1 training session (mean age, 46.7 years; 55.8% male). The mean craving response to both familiar and novel smoking cues was significantly lower for participants in the R-E group than for participants in the NR-E group at 1-month follow-up (for both cue types: t1225 = 2.1, P = .04, d = 0.44, and Δ = 0.47 [95% CI, 0.04-0.90]). The mean numbers of cigarettes smoked per day at 2 weeks and 1-month were significantly lower for the R-E group than for the NR-E group (treatment main effect: F1,68 = 5.4, P = .02, d = 0.50, and Δ = 2.4 [95% CI, 0.4-4.5]). Significant differences in physiological responses, urine cotinine level, number of days abstinent, lapse, and relapse were not observed between groups (all between P = .06 and .75)., Conclusions and Relevance: Retrieval-extinction training substantially attenuated craving to both familiar and novel smoking cues and reduced the number of cigarettes smoked per day by participants 1 month after treatment relative to extinction training alone. Between-group differences were not observed for physiological responses, cotinine level, number of days abstinent, relapse, or lapse. In summary, R-E training is a brief behavioral treatment that targets smoking-related memories and has the potential to enhance relapse prevention., Trial Registration: clinicaltrials.gov Identifier: NCT02154685.

Background and Rationale: The high prevalence of co-occurring alcohol and tobacco use underscores the importance of understanding the influence of alcohol consumption on risk factors for smoking and relapse. Alcohol has been shown to impact reactivity to smoking and stress-related cues, both of which are common antecedents to smoking and smoking relapse., Objective: The objective of the current study is to examine associations between alcohol use, cigarette craving, and stress reactivity following exposure to smoking and stress cues delivered in participants' daily lives., Methods: Using cue-reactivity ecological momentary assessment (CREMA), adult smokers (n = 138) reported cigarette craving, stress, and past hour alcohol use on a mobile device four times per day for 2 weeks, resulting in a range of 4493-5983 data points per analysis. Questions were followed by exposure to pictorial neutral, stressful, or smoking cues delivered via the mobile device. Craving and affect were re-assessed following cue exposure., Results: Results showed that recent (past hour) alcohol use was significantly associated with increases in the following: (a) tonic (non-cue-elicited) cigarette craving, (b) stress cue-elicited cigarette craving, and (c) stress cue-elicited stress reactivity, in the context of high-baseline stress. There was no significant association between alcohol use and smoking cue-elicited craving., Conclusions: Alcohol use may increase risk for smoking and relapse to smoking by increasing cigarette craving and, in certain contexts, stress following stress cue exposure. Though alcohol is known for its anxiolytic properties, under some conditions, it may increase reactivity to stress cues., Competing Interests: The authors declare that they have no conflict of interest.

The primary goal of this pilot feasibility study was to examine the effects of Mindfulness-Oriented Recovery Enhancement (MORE), a behavioral treatment grounded in dual-process models derived from cognitive science, on frontostriatal reward processes among cigarette smokers. Healthy adult ( N = 13; mean (SD) age 49 ± 12.2) smokers provided informed consent to participate in a 10-week study testing MORE versus a comparison group (CG). All participants underwent two fMRI scans: pre-tx and after 8-weeks of MORE. Emotion regulation (ER), smoking cue reactivity (CR), and resting-state functional connectivity (rsFC) were assessed at each fMRI visit; smoking and mood were assessed throughout. As compared to the CG, MORE significantly reduced smoking ( d = 2.06) and increased positive affect ( d = 2.02). MORE participants evidenced decreased CR-BOLD response in ventral striatum (VS; d = 1.57) and ventral prefrontal cortex (vPFC; d = 1.7) and increased positive ER-BOLD in VS ( d VS = 2.13) and vPFC ( d vmPFC = 2.66). Importantly, ER was correlated with smoking reduction ( r 's = .68 to .91) and increased positive affect ( r 's = .52 to .61). These findings provide preliminary evidence that MORE may facilitate the restructuring of reward processes and play a role in treating the pathophysiology of nicotine addiction., Competing Interests: There are no competing interests declared.

Given the volume and importance of research focusing on menstrual phase, a review of the strategies being used to identify menstrual phase and recommendations that will promote methodological uniformity in the field is needed. We conducted a literature review via Ovid Medline and PsycINFO. Our goal was to review methods used to identify menstrual phase and subphases in biobehavioral research studies with women who had physiologically natural menstrual cycles. Therefore, we excluded articles that focused on any of the following: use of exogenous hormones, the postpartum period, menstrual-related problems (e.g., polycystic ovarian syndrome, endometriosis), and infertility/anovulation. We also excluded articles on either younger (<18 years old) or older (>45 years old) study samples. We initially identified a total of 1,809 articles. After our exclusionary criteria were applied, 146 articles remained, within which our review identified 6 different methods used to identify menstrual phase and subphases. The most common method used was self-report of onset of menses (145/146 articles) followed by urine luteinizing hormone testing (50/146 articles) and measurement of hormones (estradiol and/or progesterone) in blood samples (49/146 articles). Overall, we found a lack of consistency in the methodology used to determine menstrual phase and subphases. We provide several options to improve accuracy of phase identification, as well as to minimize costs and burden. Adoption of these recommendations will decrease misclassification within individual studies, facilitate cross-study comparisons, and enhance the reproducibility of results., (PsycINFO Database Record (c) 2016 APA, all rights reserved.)

Introduction: Impulsivity is a multi-dimensional construct that is robustly related to cigarette smoking. While underlying factors that account for this relation are not well understood, craving has been proposed as a central mechanism linking impulsivity to smoking. In order to further refine our understanding of associations between impulsivity and cigarette craving, the current study examined the association between impulsivity and tonic and cue-elicited craving among a sample of adolescent smokers. We expected trait impulsivity would be positively associated with both tonic and cue-elicited craving, and that this relationship would be stronger among daily vs. occasional smokers., Methods: 106 smokers (ages 16-20) completed the questionnaires and reported their cigarette craving prior to and immediately following presentation of each of three counterbalanced cue types: (a) in vivo smoking, (b) alcohol, and (c) neutral cue., Results: Impulsivity was positively associated with tonic craving for daily smokers (β=.38; p=.005), but not occasional smokers (β=.01; p=.95), with a significant impulsivity x smoker group interaction (β=1.31; p=.03). Impulsivity was unrelated to craving following smoking or alcohol cue, regardless of smoker group (all p's>.16)., Conclusions: Results suggest a moderated effect in which impulsivity is positively associated with tonic craving for daily smokers, but not occasional smokers. Tonic craving may serve as a mechanism linking impulsivity, smoking persistence, and nicotine dependence among daily smokers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Within a parent study examining ovarian hormone effects on smoking cessation in women, we conducted an exploratory short-term trial of varenicline versus transdermal nicotine patch., Design: Double-blind double-dummy randomized trial., Setting: Single-site out-patient research clinic in the United States., Participants: Female smokers, ages 18-45 years and averaging ≥10 cigarettes per day for at least 6 months (n=140)., Interventions: Participants were randomized to receive a 4-week course of (a) varenicline tablets and placebo patches (n = 67) or (b) placebo tablets and nicotine patches (n=73). Two brief cessation counseling sessions were provided for all participants., Measurements: The outcome of primary clinical interest was 2-week end-of-treatment abstinence. Secondary outcomes included 1- and 4-week end-of treatment abstinence and abstinence at a post-treatment follow-up visit occurring 4 weeks after treatment conclusion. Breath carbon monoxide (≤ 10 parts per million) was used to confirm biochemically self-reported abstinence., Findings: Two-week end-of-treatment abstinence was achieved by 37.3% (25 of 67) of varenicline participants and by 17.8% (13 of 73) of nicotine patch participants [odds ratio (OR) = 2.7, 95% confidence interval (CI)=1.3-6.0, P=0.011]. One-week (44.8 versus 20.6%, OR=3.1, 95% CI=1.5-6.6, P=0.003) and 4-week (22.4 versus 9.6%, OR=2.7, 95% CI=1.0-7.2, P=0.043) end-of-treatment abstinence similarly favored varenicline, although post-treatment follow-up Russell Standard abstinence was not significantly different between groups (23.9 versus 13.7%, OR=2.0, 95% CI=0.8-4.7, P=0.126)., Conclusion: In an exploratory 4-week head-to-head trial in female smokers, varenicline, compared with nicotine patch, more than doubled the odds of end-of-treatment abstinence, although this diminished somewhat at post-treatment follow-up., (© 2015 Society for the Study of Addiction.)

Aims: To quantify the effect of negative affect (NA), when manipulated experimentally, upon smoking as measured within laboratory paradigms. Quantitative meta-analyses tested the effects of NA versus neutral conditions on (1) latency to smoke and (2) number of puffs taken., Methods: Twelve experimental studies tested the influence of NA induction, relative to a neutral control condition (n = 1190; range = 24-235). Those providing relevant data contributed to separate random-effects meta-analyses to examine the effects of NA on two primary smoking measures: (1) latency to smoke (nine studies) and (2) number of puffs taken during ad libitum smoking (11 studies). Hedge's g was calculated for all studies through the use of post-NA cue responses relative to post-neutral cue responses. This effect size estimate is similar to Cohen's d, but corrects for small sample size bias., Results: NA reliably decreased latency to smoke (g = -0.14; CI = -0.23 to -0.04; P = 0.007) and increased number of puffs taken (g = 0.14; CI = 0.02 to 0.25; P = 0.02). There was considerable variability across studies for both outcomes (I(2)  = 51 and 65% for latency and consumption, respectively). Potential publication bias was indicated for both outcomes, and adjusted effect sizes were smaller and no longer statistically significant., Conclusions: In experimental laboratory studies of smokers, negative affect appears to reduce latency to smoking and increase number of puffs taken, but this could be due to publication bias., (© 2015 Society for the Study of Addiction.)

Introduction: We previously reported that female smokers evidence greater subjective craving and stress/emotional reactivity to personalized stress cues than males. The present study employed the same dataset to assess whether females in the follicular versus luteal phase of the menstrual cycle accounted for the gender differences., Methods: Two objective criteria, onset of menses and luteinizing hormone surge (evaluated via home testing kits), were used to determine whether female smokers were in either the follicular (n = 22) or the luteal (n = 15) phase of their menstrual cycle, respectively. The females and a sample of male smokers (n = 53) were then administered a laboratory-based cue reactivity paradigm that involved assessment of craving, stress, and emotional reactivity in response to counterbalanced presentations of both a personalized stress script and neutral/relaxed script., Results: While there were no significant differences between females in the follicular versus luteal phase on any outcome measure, females in the luteal menstrual phase reported greater craving than males whereas females in the follicular phase reported greater stress and arousal than males and perceived the stress cues as more emotionally aversive than males., Conclusions: This preliminary investigation suggests that gender differences in craving versus affective responding to stress cues may, in part, be explained variation by menstrual cycle phase. Study limitations and implications of the findings for future research and treatment are briefly discussed., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Although the evidence is mixed, female smokers appear to have more difficulty quitting smoking than male smokers. Craving, stress, and negative affect have been hypothesized as potential factors underlying gender differences in quit rates., Methods: In the current study, the cue-reactivity paradigm was used to assess craving, stress, and negative affect in response to cues presented in the natural environment of cigarette smokers using ecological momentary assessment. Seventy-six daily smokers (42% female) responded to photographs (smoking, stress, and neutral) presented 4 times per day on an iPhone over the course of 2 weeks., Results: Both smoking and stress cues elicited stronger cigarette craving and stress responses compared to neutral cues. Compared with males, females reported higher levels of post-stress cue craving, stress, and negative affect, but response to smoking cues did not differ by gender., Discussion: Findings from this project were largely consistent with results from laboratory-based research and extend previous work by measuring response to cues in the natural environment of cigarette smokers. This study extends previous cue reactivity ecological momentary assessment research by using a new platform and by measuring response to stress cues outside of the laboratory. Findings from this project highlight the importance of addressing coping in response to stress cues in clinical settings, especially when working with female smokers., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: To determine the effect of ovarian hormones on smoking, we conducted a systematic review of menstrual cycle effects on smoking (i.e., ad lib smoking, smoking topography, and subjective effects) and cessation-related behaviors (i.e., cessation, withdrawal, tonic craving, and cue-induced craving)., Methods: Thirty-six papers were identified on MEDLINE that included a menstrual-related search term (e.g., menstrual cycle, ovarian hormones), a smoking-related search term (e.g., smoking, nicotine), and met all inclusion criteria. Thirty-two studies examined menstrual phase, 1 study measured hormone levels, and 3 studies administered progesterone., Results: Sufficient data were available to conduct meta-analyses for only 2 of the 7 variables: withdrawal and tonic craving. Women reported greater withdrawal during the luteal phase than during the follicular phase, and there was a nonsignificant trend for greater tonic craving in the luteal phase. Progesterone administration was associated with decreased positive and increased negative subjective effects of nicotine. Studies of menstrual phase effects on the other outcome variables were either small in number or yielded mixed outcomes., Conclusions: The impact of menstrual cycle phase on smoking behavior and cessation is complicated, and insufficient research is available upon which to conduct meta-analyses on most smoking outcomes. Future progress will require collecting ovarian hormone levels to more precisely quantify the impact of dynamic changes in hormone levels through the cycle on smoking behavior. Clarifying the relationship between hormones and smoking-particularly related to quitting, relapse, and medication response-could determine the best type and timing of interventions to improve quit rates for women., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature., Methods: Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly., Results: Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females., Conclusions: This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medication-based treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans., Methods: In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session., Results: DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions., Conclusions: 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence., Scientific Significance: Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity., (© American Academy of Addiction Psychiatry.)

Background: As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence., Methods: Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS)., Results: Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR - NR), such that higher dependence was associated with more prominent NR motives for smoking., Conclusions: Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Smoking initiation usually begins in adolescence, but how and for whom nicotine dependence emerges during this period is unclear. The cue-reactivity paradigm is well suited to examine one marker of dependence: craving-related stimulus control, i.e., the ability of environmental cues to elicit craving to smoke. This study examined the effects of both level of smoking involvement (daily vs. occasional smoking) and gender on reactivity to both smoking and alcohol cues., Methods: Young (age range 16-20; 42% female) daily (n = 55) and occasional (n = 52) smokers were exposed to each of three counterbalanced cues: (a) in vivo smoking (e.g., sight, smell, lighting of cigarette), (b) alcohol (e.g., opening, pouring, and smell of preferred beverage), and (c) neutral cue., Results: Daily smokers exhibited higher levels of tonic (i.e., noncue-elicited) craving than did occasional smokers. Both groups showed significant increases in craving in response to cues (i.e., cue-elicited craving), with little evidence that cue-elicited craving differed between groups. Females were more cue reactive to both the alcohol and smoking cues than males, particularly for the positively reinforced aspects of smoking (i.e., hedonic craving). There were no gender × group interaction effects in response to either the alcohol or the smoking cue., Conclusions: Findings show the presence of cue-elicited craving even among occasional smokers and are consistent with literature demonstrating heightened sensitivity to environmental cues among females. Cue-elicited craving may be one mechanism that contributes to the maintenance of smoking behavior and perhaps to the development of nicotine dependence within early stage smokers.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e., smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers., (© 2013 Elsevier Ltd. All rights reserved.)

Rationale: The reinforcing properties of nicotine may be, in part, derived from its ability to enhance certain forms of cognitive processing. Several animal and human studies have shown that nicotine increases prepulse inhibition (PPI) of the startle reflex. However, it remains unclear whether these effects are related to smoking susceptibility., Objectives: The current study examined the effects of intravenously delivered nicotine on PPI in smokers and non-smokers, as well as its association with a quantitative index of familial smoking., Methods: The sample consisted of 30 non-smokers and 16 smokers, who completed an initial assessment, followed on a separate day by a laboratory assessment of PPI prior to and following each of two intravenous nicotine infusions. Separate doses were used in smoker and non-smoker samples., Results: Analyses indicated that both nicotine infusions acutely enhanced PPI among non-smokers, and this enhancement was positively related to the degree of smoking among first and second-degree relatives. Smokers also displayed PPI enhancement after receiving the first infusion, but this effect was unrelated to familial smoking., Conclusions: These data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk.

Background: The development of addiction is marked by a pathological associative learning process that imbues incentive salience to stimuli associated with drug use. Recent efforts to treat addiction have targeted this learning process using cue exposure therapy augmented with d-cycloserine (DCS), a glutamatergic agent hypothesized to enhance extinction learning. To better understand the impact of DCS-facilitated extinction on neural reactivity to drug cues, the present study reports fMRI findings from a randomized, double-blind, placebo-controlled trial of DCS-facilitated cue exposure for cocaine dependence., Methods: Twenty-five participants completed two MRI sessions (before and after intervention), with a cocaine-cue reactivity fMRI task. The intervention consisted of 50mg of DCS or placebo, combined with two sessions of cocaine cue exposure and skills training., Results: Participants demonstrated cocaine cue activation in a variety of brain regions at baseline. From the pre- to post-study scan, participants experienced decreased activation to cues in a number of regions (e.g., accumbens, caudate, frontal poles). Unexpectedly, placebo participants experienced decreases in activation to cues in the left angular and middle temporal gyri and the lateral occipital cortex, while DCS participants did not., Conclusions: Three trials of DCS-facilitated cue exposure therapy for cocaine dependence have found that DCS either increases or does not significantly impact response to cocaine cues. The present study adds to this literature by demonstrating that DCS may prevent extinction to cocaine cues in temporal and occipital brain regions. Although consistent with past research, results from the present study should be considered preliminary until replicated in larger samples., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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., (© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.)

Rationale/objectives: This study examined the effects of propranolol vs. placebo, administered immediately after a "retrieval" session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent "test" session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up., Methods: CD participants received either 40 mg propranolol or placebo immediately following a "retrieval" CCE session. The next day, participants received a "test" session of CCE that was identical to the "retrieval" session except no medication was administered. Participants underwent a "follow-up" CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions., Results: Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use., Conclusions: This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted.

Rationale: D-Cycloserine (DCS), a partial glutamate N-methyl-D-aspartate (NMDA) receptor agonist, enhances extinction of conditioned fear responding; preliminary data suggest that it may facilitate extinction of drug cue reactivity., Objective: This study investigates DCS effects on cocaine cue craving and drug use in cocaine-dependent subjects., Methods: Thirty-two subjects were randomly assigned to receive (1) DCS only, (2) DCS before sessions 1 and 3, placebo (PBO) before session 2, or (3) PBO only 15-min before each of 3 1-h cocaine cue exposure sessions conducted 1 day apart. Craving ratings were obtained before, during, and after sessions. Drug use and cue-induced craving were assessed 1 week after the last cue session., Results: Repeated presentation of cocaine cues resulted in decreased craving both within and between sessions. DCS did not facilitate extinction learning and may have enhanced craving. The group that received three doses of DCS had significantly higher craving than the PBO group at the baseline ratings taken before sessions 2 and 3, as well as significantly higher cue-induced craving at follow-up. The group that received two doses of DCS did not differ from the PBO group. There were no group differences in postextinction cocaine use., Conclusions: The reduction of cocaine cue reactivity in the PBO group suggests that the study procedures were sufficient to produce extinction. Under these conditions, DCS did not facilitate extinction and may have enhanced craving. Further studies of glutamatergic agents and extinction in cocaine dependence should include consideration of procedural variables that could have a major impact on study outcomes.