Naltrexone/bupropion for binge-eating disorder: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Binge-eating disorder (BED) is a prevalent psychiatric disorder associated with obesity. Few evidence-based treatments exist for BED, particularly pharmacological options. This study tested the efficacy of naltrexone/bupropion for BED. METHODS: A randomized, double-blind, placebo-controlled, 12-week trial tested naltrexone/bupropion for BED with and without obesity. Eighty-nine patients (70.8% women, 69.7% White, mean age 45.7 y, mean BMI 35.1 kg/m2 , 77.5% with BMI ≥ 30 kg/m2 ) were randomized to placebo (n = 46) or naltrexone/bupropion (n = 43), with randomization stratified by obesity status and gender; 92.1% completed post-treatment assessments. RESULTS: Mixed models of binge-eating frequency revealed significant reductions that did not differ significantly between naltrexone/bupropion and placebo. Logistic regression of binge-eating remission rates revealed that naltrexone/bupropion and placebo did not differ significantly. Obesity status did not predict, or moderate, binge-eating outcomes considered either continuously or categorically. Mixed models revealed that naltrexone/bupropion was associated with significantly greater percentage weight loss than placebo. Logistic regression revealed that naltrexone/bupropion had significantly higher rates of attaining ≥5% weight loss than placebo (27.9% vs. 6.5%). Obesity status did not predict or moderate weight-loss outcomes. CONCLUSIONS: Naltrexone/bupropion did not demonstrate effectiveness for reducing binge eating relative to placebo but showed effectiveness for weight reduction in patients with BED. Obesity status did not predict or moderate medication outcomes.

The role of sex hormones in targeting stress-induced tobacco craving, stress-reactivity, and smoking with guanfacine among women who smoke.

Women who smoke are particularly vulnerable to tobacco craving, smoking behaviors, and relapse in the context of stress when compared to men who smoke. One factor in this sex difference may be sex hormones, including estradiol and progesterone; however, smoking cessation medication trials often do not explore the impact of sex hormones on drug effects. This secondary analysis of a double-blind, placebo-controlled study explored the impact of levels of actual estradiol and progesterone on guanfacine, a noradrenergic α2a agonist, which attenuates stress-induced smoking behaviors in women. Women who smoke (n = 43) completed a stress induction laboratory paradigm followed by an ad-libitum smoking period. Assessment of tobacco craving, and stress-reactivity (via cortisol response) occurred pre- and post-stress induction. Results indicated that guanfacine attenuated stress-induced tobacco craving (F = 10.94, p = 0.02) and cortisol response (F = 14.23, p < 0.001); however, high levels of estradiol overrode guanfacine's effect on craving (F = 4.00, p = 0.05), cortisol response (F = 14.23, p < 0.001), and smoking during the ad-libitum period (F = 12.23, p = 0.001). Additionally, progesterone proved to be protective against tobacco craving and enhanced guanfacine's medication effect on craving (F = 5.57, p = 0.02). The present study found that sex hormones had a significant impact on medication effects in a smoking cessation trial and thus underscore the importance of examining the role of sex hormones in future medication trials.

Sex effects in predictors of smoking abstinence and neuropsychiatric adverse events in the EAGLES trial.

Significance There are sex effects in abstinence outcomes across all smoking cessation medications, but there is limited information regarding sex effects on cessation-related neuropsychiatric adverse events (NPSAEs) or interactions with psychiatric status. METHODS: Secondary analysis of data from EAGLES of 8144 adults who smoke cigarettes randomized to varenicline, bupropion, nicotine patch or placebo. Design characteristics included region (within/outside US), psychiatric cohort (absent/present), and treatment. Baseline variables included demographics, smoking history, prior use of study treatments, lifetime suicide-related history, and prior psychiatric co-morbidities and medication use. Design characteristics were forced into logistic regressions models, and then interactions among sex, design elements, and baseline characteristics were evaluated for NPSAEs and 6-month cessation outcomes. RESULTS: Findings demonstrated a significant interaction of sex and race (p < 0.02); Black women were more likely to report NPSAEs than Black men. For cessation outcomes, there were no significant interactions with psychiatric cohort and sex. Women vs men with higher baseline levels of smoking had lower odds of continuous abstinence. Women vs men who used varenicline previously had lower odds of continuous abstinence. For 6-month point prevalence, sex interacted with baseline cigarettes per day (p < 0.01) similar to the interaction for continuous abstinence. Sex interacted with medication (p < 0.03), such that women vs men had relatively greater success at achieving point prevalence abstinence on varenicline. CONCLUSIONS: Overall, results demonstrated important sex and racial differences in the incidence of NPSAEs, but psychiatric status did not interact with sex on cessation outcomes. Findings did support prior work demonstrating relative increased efficacy of varenicline for women.

Sex steroid hormone levels associated with dopamine D2/3 receptor availability in people who smoke cigarettes.

Introduction: Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes. Nicotine binds to nicotinic acetylcholine receptors, facilitating dopamine release in striatal and cortical brain regions. Dysregulated dopamine D2/3 receptor signaling in the dorsolateral prefrontal cortex (dlPFC) is associated with cognitive deficits such as impairments in attention, learning, and inhibitory control that impede quit attempts. Sex steroid hormones, such as estradiol and progesterone, influence drug-taking behaviors, through dopaminergic actions, suggesting that their influence may explain sex differences in tobacco smoking. The goal of this study was to relate dlPFC dopamine metrics to sex steroid hormone levels in people who smoke and healthy controls. Methods: Twenty-four (12 women) people who smoke cigarettes and 25 sex- and age-matched controls participated in two same-day [11C]FLB457 positron emission tomography scans, one before and one after amphetamine administration. D2R availability (BPND) at baseline and after amphetamine administration was calculated. On the same day, plasma samples were collected for the analysis of sex steroid hormone levels: estradiol, progesterone, and free testosterone. Results: Women who smoke had trending lower levels of estradiol than their sex-matched counterparts. Men who smoke had higher levels of estradiol and trending higher levels of free testosterone than their sex-matched counterparts. Among women only, lower estradiol levels were significantly associated with lower pre-amphetamine dlPFC BPND. Discussion/conclusion: This study demonstrated that lower estradiol levels are associated with lower dlPFC D2R availability in women which may underlie difficulty resisting smoking.

Developmental trajectories of alcohol and cannabis concurrent use in a nationally representative sample of United States youths.

BACKGROUND: Previous studies have identified common trajectories of single type substance use over the course of adolescence; however, no study to date has examined joint trajectories of cannabis and alcohol concurrent use. Given that expansion of legal cannabis has increased availability, it is important to understand patterns of concurrent use in adolescents and factors that place male and female youth at risk for harmful trajectories of concurrent use. The current study sought to identify joint trajectories of cannabis and alcohol use - and predictors of harmful use trajectories - among male and female adolescents. METHOD: We used 4 waves of data from 6997 early adolescent participants (age 12-14 years at Wave 1) in the Population Assessment of Tobacco and Health, a nationally representative longitudinal study in the United States. Participants reported their cannabis and alcohol use reassessed yearly for 5 years (2013-2018). We used joint trajectory growth mixture modeling to identify trajectory groups as defined by changes in alcohol and cannabis use over time. RESULTS: Five classes of alcohol and cannabis concurrent use trajectories were identified. Both internalizing and externalizing symptoms at Wave 1 increased the odds of membership in trajectory groups characterized by more harmful use trajectories. Internalizing symptomatology was a stronger predictor of membership in escalating use trajectories among girls, whereas externalizing symptomatology stronger predictor among boys. CONCLUSIONS: These findings underscore the utility of jointly considering alcohol and cannabis use when describing common developmental trajectories of use and identifying risk factors for trajectories characterized by harmful use.

Liquor consumption is associated with other medical conditions in females who consume alcohol.

Background: Our group previously identified that females with AUD and females engaging in heavy or extreme binge drinking were more likely to report cancers and other medical conditions compared to their male counterparts. This analysis aimed to extend our previous findings to examine relationships between sex and consumption of alcohol by type on past year medical condition diagnoses. Methods: Data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309) was used to evaluate associations between sex (female vs. male) and alcohol type (liquor, wine, beer, coolers) on past year self-reported doctor-confirmed medical conditions, controlling for frequency of alcohol consumption. Results: A significant interaction demonstrated that females who consumed liquor were more likely to have other medical conditions (OR=1.95) compared to males who consumed liquor. Females who consumed wine in the past year were less likely to have cardiovascular conditions (OR=0.81) compared to males who consumed wine. Those who consumed liquor had increased odds of pain, respiratory, and other conditions (OR=1.11 - 1.21). Females were 1.5 times more likely to have cancers or pain, respiratory, and other medical conditions compared to males (OR=1.36 - 1.81). Conclusions: Results identify that consumption of higher alcohol content drinks (i.e., liquor) is associated with past year self-reported doctor- or health-professional confirmed medical conditions in females compared to males consuming the same high alcohol content beverage. Not only should AUD status and risky drinking be considered in the clinical care of individuals with poorer health but also alcohol type, especially higher alcohol content beverages.

Testing the efficacy of real-time fMRI neurofeedback for training people who smoke daily to upregulate neural responses to nondrug rewards.

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities.

Lower Dopamine D2/3 Receptor Availability is Associated With Worse Verbal Learning and Memory in People Who Smoke Cigarettes.

INTRODUCTION: Tobacco smoking is a major public health burden. The mesocortical dopamine system-including the dorsolateral prefrontal cortex (dlPFC)-plays an important role in cognitive function. Dysregulated dopamine signaling in dlPFC is associated with cognitive deficits such as impairments in attention, learning, working memory, and inhibitory control. We recently showed that dlPFC dopamine D2/3-type receptor (D2R) availability was significantly lower in people who smoke than in healthy-controls and that dlPFC amphetamine-induced dopamine release was lower in females who smoke relative to males who smoke and female healthy-controls. However, we did not examine whether the smoking-related dopamine deficits were related to cognitive deficits. AIMS AND METHODS: The goal of this study was to relate dopamine metrics to cognitive performance in people who smoke and healthy-controls. In total 24 (12 female) people who smoke cigarettes and 25 sex- and age-matched healthy-controls participated in two same-day [11C]FLB457 positron emission tomography (PET) scans before and after amphetamine administration. Two outcome measures were calculated-D2R availability (non-displaceable binding potential; BPND) and amphetamine-induced dopamine release (%ΔBPND). Cognition (verbal learning and memory) was assessed with a computerized test from the CogState battery (International Shopping List). RESULTS: People who smoke had significantly worse immediate (p = .04) and delayed (p = .03) recall than healthy-controls. Multiple linear regression revealed that for people who smoke only, lower D2R availability was associated with worse immediate (p = .04) and delayed (p < .001) recall. %ΔBPND was not significantly related to task performance. CONCLUSION: This study demonstrated that lower dlPFC D2R availability in people who smoke is associated with disruptions in cognitive function that may underlie difficulty with resisting smoking. IMPLICATIONS: This is the first study to directly relate dopamine metrics in the prefrontal cortex to cognitive function in people who smoke cigarettes compared to healthy-controls. The current work included a well-characterized subject sample with regards to demographic and smoking variables, as well as a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature by relating dopamine metrics to cognition in people who smoke, providing a better understanding of brain-behavior relationships.

Licit and illicit drug use across trimesters in pregnant women endorsing past-year substance use: Results from National Survey on Drug Use and Health (2009-2019).

PURPOSE: Given the health consequences, perinatal substance use is a significant public health concern, especially as substance use rates increase among women; ongoing data regarding the rates of substance use across trimesters of pregnancy is needed. METHODS: The present study utilized cross-sectional population-based data from the National Survey of Drug Use and Health (NSDUH) between 2009 and 2019. We aimed to explore both licit and illicit substance use assessed within each trimester among women endorsing past-year substance use. The NSDUH sample included 8,530 pregnant women. RESULTS: Perinatal substance use was less prevalent among women in later trimesters; however, past-month substance use was observed for all substances across trimesters. The prevalence of past-month licit substance use among pregnant women ranged from 5.77 to 22.50% and past-month illicit substance use ranged from 4.67 to 14.81%. In the second trimester, lower odds of past-month substance use were observed across tobacco, alcohol, and marijuana (odds ratios [ORs] ranging from 0.29 to 0.47), when compared to the first trimester. A similar lower rate of past-month substance use was observed in the third trimester compared to the first trimester, across tobacco, alcohol, and marijuana use, as well as cocaine, prescription pain medication, and tranquilizer use (ORs ranging from 0.02 to 0.42). The likelihood of polysubstance use was lower among women in the second and third trimesters compared to the first trimester (ORs ranging from 0.09 to 0.46). CONCLUSION: Findings indicate that a minority of women continue to use substances across all trimesters. This is especially true among women using licit substances and marijuana. These results highlight the need for improved interventions and improved access to treatment for these women.

Consideration of sex and gender differences in addiction medication response.

Substance use continues to contribute to significant morbidity and mortality in the United States, for both women and men, more so than another other preventable health condition. To reduce the public health burden attributable to substances, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have identified that medication development for substance use disorder is a high priority research area. Furthermore, both Institutes have stated that research on sex and gender differences in substance use medication development is a critical area. The purpose of the current narrative review is to highlight how sex and gender have been considered (or not) in medication trials for substance use disorders to clarify and summarize what is known regarding sex and gender differences in efficacy and to provide direction to the field to advance medication development that is consistent with current NIH 'sex as a biological variable' (SABV) policy. To that end, we reviewed major classes of abused substances (nicotine, alcohol, cocaine, cannabis, opioids) demonstrating that, sex and gender have not been well-considered in addiction medication development research. However, when adequate data on sex and gender differences have been evaluated (i.e., in tobacco cessation), clinically significant differences in response have been identified between women and men. Across the other drugs of abuse reviewed, data also suggest sex and gender may be predictive of outcome for some agents, although the relatively low representation of women in clinical research samples limits making definitive conclusions. We recommend the incorporation of sex and gender into clinical care guidelines and improved access to publicly available sex-stratified data from medication development investigations.

Changes in alcohol use by cannabis use status among adolescents and young adults in the United States: Emerging evidence for both substitution and complementarity.

BACKGROUND: The majority of adolescents and young adults (AYA) who use cannabis also use alcohol. Although cannabis use is increasing in the United States (US), it is not known whether the increase contributes to either increased co-use of alcohol and cannabis (e.g., complementarity) or replacement of alcohol with cannabis (e.g., substitution). The current study estimated the prevalence of alcohol use by cannabis use status among US AYA ages 12 to 25 in 2018 and trends in alcohol use by cannabis use status from 2002 to 2018. METHODS: Data were drawn from the 2002 to 2018 National Survey on Drug Use and Health public use data files. The analytic sample included AYA ages 12 to 25 (2018 sample, n = 26,924; total combined sample 2002 to 2018, n = 576,053). Linear and logistic regression models were used to estimate past-month alcohol use, daily alcohol use, and average quantity of alcohol consumed among AYA with and without past-month cannabis use from 2002 to 2018. RESULTS: In 2018, any alcohol use and daily alcohol use were significantly more common among AYA who used cannabis use than those who did not use cannabis. Overall, any alcohol use, daily alcohol use, and average drinks per day declined from 2002 to 2018 among AYA irrespective of recent cannabis use. However, the decline in any alcohol use, daily alcohol use, and average alcohol drinks per day was more rapid among AYA who used cannabis (daily and nondaily) than those who did not use cannabis. The rate of decline in average alcohol drinks per day was also higher among AYA with daily compared to nondaily cannabis use. CONCLUSIONS: Even with declines in alcohol use over time, drinking is much more common among AYA who report cannabis than those without recent cannabis use, which is consistent with complementarity. Yet, because the decline in alcohol use has been more rapid among AYA who use cannabis, there is also evidence of substitution. Thus, the current data on alcohol and cannabis use are consistent with both complementarity and substitution. However, these relationships may change as cannabis legalization expands over time.

Prospective Associations of Pain Intensity and Substance Use in the United States Population: A Cross-Lagged Panel Analysis.

OBJECTIVE: Pain is associated with increased risk for harmful substance use. Substance use also may increase levels of pain, suggesting that these two factors may reciprocally increase risk. The current study examined the reciprocal association between pain and substance use outcomes (i.e., alcohol, cannabis, and painkillers/sedatives/tranquilizers [PSTs]) longitudinally in a nationally representative cohort of non-incarcerated U.S. citizens. METHOD: Adult (≥18 years old) survey data from Waves 2-4 of the Population Assessment of Tobacco and Health (PATH) study were used. The PATH is a nationally representative multiwave cohort survey (Wave 2: October 2014-October 2015, Wave 3: October 2015-October 2016, Wave 4: December 2016-January 2018). Cross-lagged panel models were used to estimate the reciprocal effects of pain intensity and substance use on subsequent changes in both variables. Substance use outcomes were substance use problems and greater-than-weekly use for cannabis and PSTs, total past-month drinks, and alcohol use exceeding moderate drinking guidelines. All models controlled for autoregressive effects and demographic covariates. RESULTS: Pain intensity showed a positive prospective association with all substance use outcomes. All cannabis and PST use were positively associated with subsequent pain intensity. Alcohol use problems also predicted higher levels of pain intensity. Neither total past-month drinks nor exceeding moderate drinking guidelines predicted subsequent pain intensity. CONCLUSIONS: Pain and substance use show a reciprocal association and may act in a positive feedback loop to worsen both conditions over time in people with a history of use.

Sex and alcohol use disorder predict the presence of cancer, respiratory, and other medical conditions: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III.

BACKGROUND: Women experience greater health consequences of alcohol compared to their male counterparts. In recent years, rates of drinking and heavy alcohol use have increased in women while remaining relatively steady in men. Thus, our aim was to newly examine associations between sex, AUD, and the presence of medical conditions in a large nationally representative, cross-sectional dataset. METHODS: Using data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309), we evaluated relationships among sex and DSM-5 AUD, and their association with past year clinician-confirmed medical conditions. RESULTS: Women were 1.5 to 2 times more likely to be diagnosed with a past year cancer, pain, respiratory, or other significant medical condition compared to men (odds ratio [OR] = 1.331-2.027). Individuals with an ongoing DSM-5 AUD were nearly 1.5 to 2 times more likely to report a confirmed past year liver, cardiovascular, cancer, or other significant medical condition compared to those without an AUD (OR = 1.437-2.073). Interactive effects demonstrated that women with an ongoing AUD were 2 to 3 times more likely to report a past year doctor- or health professional-confirmed medical condition compared to men; specifically, respiratory conditions and cancers (OR = 1.767-2.713). CONCLUSIONS: Results identify that AUD is a critical factor associated with disease that spans organ systems. Associations between AUD and respiratory conditions or cancers are particularly robust in women. Effective interventions for a broad spectrum of medical conditions should consider the role of problematic alcohol use, especially given that rates of drinking in women are increasing.

Sex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders.

Stress and trauma exposure disturbs stress regulation systems and thus increases the vulnerability for stress-related disorders which are characterized by negative affect, including major depressive disorder, anxiety disorders and posttraumatic stress disorder. Similarly, stress and trauma exposure results in increased vulnerability to problematic alcohol use and alcohol use disorder, especially among women, who are more likely to drink to cope with negative affect than their male counterparts. Given these associations, the relationship between stress-related disorders and alcohol use is generally stronger among women leading to complex comorbidities across these disorders and alcohol misuse. This review highlights the therapeutic potential for progestogen- and androgen-derived neurosteroids, which affect both stress- and alcohol-related disorders, to target the overlapping symptoms related to negative affect. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'

Risk drinking levels and sex are associated with cancer and liver, respiratory, and other medical conditions.

Background: Heavy alcohol use is associated with increased risk of alcohol-related health consequences. Alcohol consumption has increased in females in the last fifteen years and females are more likely to experience exacerbated health risks due to drinking. Our group identified that females with AUD were more likely to report respiratory conditions or cancers compared to their male counterparts. This analysis sought to further examine relationships between sex and alcohol use on medical conditions by using the new 2020 U.S. Dietary Guidelines risk drinking levels. Methods: Data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309) was used to evaluate associations between sex (female vs. male) and alcohol risk drinking levels (abstainer, binge, heavy, extreme binge vs. moderate drinking) on past year self-reported doctor-confirmed medical conditions). Results: Females were 1.5 to 2 times more likely to have pain, respiratory, or other medical conditions in the past year (odds ratio [OR]=1.46-2.11) vs. males. Significant interactions demonstrated that heavy drinking females or extreme binge drinking females were 2 to 3 times more likely to have cancers or other conditions (OR=1.95-2.69) vs. males at the same risk drinking level. Female abstainers were more likely than male abstainers to have other medical conditions (OR=1.77). Conclusions: Consistent with our previous findings, results identify that higher risk drinking levels are associated with the presence of past year self-reported doctor-confirmed medical conditions spanning organ systems, particularly in females. Treatment for high-risk drinking should be considered in the clinical care of individuals with significant medical conditions.

A prospective study of the association between rate of nicotine metabolism and alcohol use in tobacco users in the United States.

BACKGROUND: Rate of nicotine metabolism has been identified as a biochemical risk factor for nicotine use and dependence; however, its role in alcohol consumption and related outcomes is not well understood. The current research examined nicotine metabolism rate as a risk factor for alcohol use among current tobacco users. We also examined sex differences in these associations. METHOD: Data were taken from Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) study, a national longitudinal study of tobacco use and associated health outcomes. The nicotine metabolite ratio (NMR) was calculated as the ratio of trans-3' hydroxycotinine to cotinine in urine samples provided at wave 1. Alcohol use outcomes included past 30-day NIAAA-defined hazardous drinking status, total drinks, and alcohol-related consequences. All analyses controlled for alcohol use at Wave 1. RESULTS: NMR at Wave 1 predicted increased odds of meeting hazardous drinking criteria, adjusted odds ratio (aOR) = 1.14, 95 % CI = 1.06; 1.23, p = 0.001, greater total alcohol consumption amount, adjusted rate ratio (aRR) = 1.21, 95 % CI = 1.12; 1.30, p < 0.001, and more alcohol consequences, aRR = 1.07, 95 % CI = 1.01; 1.13, p = 0.018, at wave 2. No significant sex differences were identified. NMR remained a significant predictor of alcohol use in models controlling for severity of nicotine exposure in cigarette smokers. CONCLUSIONS: NMR may be a shared risk factor for harmful nicotine and alcohol use that contributes to their co-occurrence.

A randomized controlled trial protocol for engaging distress tolerance and working memory to aid smoking cessation in low socioeconomic status (SES) adults.

Low income and low educational attainment are among the strongest predictors of both smoking prevalence and lapse (i.e., return) to smoking after cessation attempts. Treatment refinement is limited by inadequate knowledge of the specific lapse- or relapse-relevant vulnerabilities characteristic of populations that should be the target of treatment. In the context of a randomized clinical trial design, we describe an experimental medicine approach for evaluating the role of 2 specific lapse-relevant targets relative to the higher stress characteristic of low-socioeconomic contexts: low distress tolerance and low working memory capacity. Furthermore, we use an innovative approach for understanding risk of smoking lapse in smokers undergoing a quit attempt to examine candidate mechanistic targets assessed not only during nicotine use, but also during the conditions smokers will face upon a cessation attempt-during stressful nicotine-deprivation windows. This study is designed to show the incremental value of assessments during deprivation windows, in part because of the way in which specific vulnerabilities are modified by, and interact with, the heightened stress and withdrawal symptoms inherent to nicotine-deprivation states. Specifically, the study is designed to evaluate whether a novel mindfulness intervention (mindfulness combined with interoceptive exposure) can improve upon existing mindfulness interventions and extend therapeutic gains to the modification of mechanistic targets assessed in high-stress or negative affectivity contexts. The overall goal is to validate mechanistic targets and associated interventions for the purpose of expanding treatment options for at-risk smokers. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Associations Between Nicotine Metabolite Ratio and Gender With Transitions in Cigarette Smoking Status and E-Cigarette Use: Findings Across Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study.

INTRODUCTION: Nicotine metabolite ratio (NMR), the ratio of trans 3'-hydroxycotinine to cotinine, is a biomarker of nicotine metabolism. Discrepant findings among clinical trials and population-based studies warrant replication on whether higher NMR, or faster nicotine metabolism, is associated with quitting cigarette smoking. Associations of NMR and e-cigarette use are largely unknown, as well as the relationship between NMR and gender on quitting cigarette smoking or e-cigarette use. METHODS: The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative, longitudinal cohort study assessing tobacco use in the US population. In the current study, the PATH (waves 1 and 2; adult interviews) was used to evaluate longitudinal predictions in relationships among NMR and gender and their association with transitions (quit vs. current stable) in cigarette smoking status and e-cigarette use status across waves 1 and 2 of the PATH study. RESULTS: NMR and gender were not significantly associated with quit behavior for combustible cigarettes. Regarding e-cigarettes, a significant two-way interaction demonstrated that women with higher NMR were less likely to quit e-cigarette use compared to women with lower NMR (odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.02-0.57; p = .01). CONCLUSIONS: Findings identify that women with faster nicotine metabolism were 10 times less likely to quit e-cigarettes compared to women with slower nicotine metabolism across waves 1 and 2 of the PATH study. Results suggest that NMR may be used as a biomarker for transitions in e-cigarette quit behavior for women. IMPLICATIONS: Findings identify that women with faster nicotine metabolism were 10 times less likely to quit e-cigarettes compared to women with slower nicotine metabolism. Results suggest that NMR may be used as a biomarker for transitions in e-cigarette quit behavior for women. Establishing parameters for NMR collection and for the use of NMR as a biomarker for cigarette smoking behavior and e-cigarette use is an important next step, and may have implications for early intervention and treatment for cessation.

Prospective association of e-cigarette and cigarette use with alcohol use in two waves of the Population Assessment of Tobacco and Health.

BACKGROUND AND AIMS: Prior cross-sectional research finds that electronic cigarette (e-cigarette) use clusters with higher rates of harmful alcohol consumption in the United States adult population. The current study examined prospectively the association between e-cigarette use, cigarette use and the combined use of e-cigarettes and tobacco cigarettes and alcohol use outcomes. DESIGN: A nationally representative multi-wave cohort survey (wave 1: September 2013-December 2014, wave 2: October 2014-October 2015). SETTING: United States. PARTICIPANTS: A representative sample of civilian, non-institutionalized adults who completed waves 1 and 2 of the Population Assessment of Tobacco and Health survey (n = 26 427). MEASUREMENTS: Participants were categorized into exposure groups according to their e-cigarette and cigarette use during wave 1. Past 30-day alcohol use outcomes were (1) National Institute on Alcohol Abuse and Alcoholism (NIAAA)-defined hazardous alcohol use, (2) total alcohol drinks consumed and (3) alcohol-related consequences. FINDINGS: After controlling for socio-demographic risk factors and alcohol use at wave 1, all exposure groups showed higher odds of hazardous alcohol use [adjusted odds ratios (aORs) = 2.05-2.12, all P < 0.001] and reported higher past-month total drinks (B = 0.46-0.70, all P < 0.001) and more alcohol consequences (B = 0.63-0.89, all P ≤ 0.10) at wave 2 compared with non-users. Cigarette users (B = 0.24, P = 0.038) and dual e-cigarette/cigarette users (B = 0.32, P = 0.038) reported higher past-month total drinks compared with e-cigarette users. There was no conclusive evidence that non-daily use of e-cigarettes or cigarettes predicted poorer alcohol use outcomes compared with daily use. CONCLUSIONS: In the United States between 2013 and 2015, after adjustment for socio-demographic characteristics, cigarette and e-cigarette use were associated with alcohol use 1 year later.