N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.

In the Presence of Parents: Parental Heterosexism and Momentary Negative Affect and Substance Craving Among Sexual Minority Youth.

PURPOSE: We examined the influence of parental heterosexism on in vivo negative affect and substance craving among sexual minority youth (SMY) who use nicotine and other substances, and if that relation was strengthened when in the presence of their parent(s). METHODS: SMY (n = 42, ages 15-19) completed baseline assessments, including experiences of parental heterosexism (PH), and a 30-day ecological momentary assessment. Ecological momentary assessment reports included affective states (i.e., anger, anxiety, depression), substance craving (i.e., nicotine, cannabis, alcohol), and other contextual factors (e.g., presence of parents). Multilevel logistic regression models evaluated the study hypotheses. RESULTS: PH was associated with greater odds of reporting in-the-moment anger, depression, cannabis craving, and alcohol craving. Parental presence was associated with lower odds of reporting anxiety or depression, and greater odds of reporting nicotine craving. There was a significant interaction when predicting the odds of reporting anxiety. For SMY low in PH, parental presence was related to lower odds of reporting anxiety. As PH increased, parental presence had diminishing associations with the odds of reporting anxiety. DISCUSSION: Parenting behaviors can serve as protective and risk factors for negative affect and substance craving among SMY. Improving family-based interventions for SMY may be integral for enhancing healthy development and reducing health disparities.

Momentary Associations Among Minority Stress, Craving, Affect, and Nicotine Use Among Sexual Minority Youth.

OBJECTIVES: Sexual minority youth are more likely to use nicotine relative to heterosexual youth. The minority stress model posits these disparities are partly due to unique stress (i.e., minority stress) specific to their stigmatized identities. However, there is a dearth of research exploring the fine-grained dynamic interplay between minority stressors, mediating processes, and nicotine use in sexual minority youth's daily lives and natural environment. We leveraged ecological momentary assessment over a 30-day monitoring period to test the mediating effects of craving and negative and positive affect on the momentary associations between minority stressors and subsequent nicotine use among sexual minority youth who were active nicotine users and recruited from the community. METHODS: Participants were 85 nicotine users, ages 15-19 years old (M age = 17.96, SD = 1.10; 56.6% cisgender female; 56.6% bisexual; 73.5% non-Hispanic White) and half (51.8%) were daily nicotine users. RESULTS: Results indicated that exposure to a minority stressor was associated with momentary elevations in nicotine craving and negative affect and decreases in positive affect. Nicotine craving and positive affect were also associated with greater probability of subsequent nicotine use. The associations between minority stressors and subsequent nicotine use were mediated through craving and positive, but not negative affect. CONCLUSIONS: Our findings provide the first ecological momentary assessment evidence of these associations among sexual minority youth and help support and advance both addictions and sexual minority-specific models (e.g., minority stress) of nicotine use among youth.

Minority Stress and Nicotine Use and Dependence among Sexual Minority Youth.

Sexual minority youth (SMY), especially those who are plurisexual (e.g. bisexual, pansexual, queer), are more likely to use nicotine or develop nicotine dependence than their heterosexual peers, and this disparity is often attributed to minority stress (e.g. discrimination). This study tested the association between minority stress and nicotine use and dependence among SMY and examined the moderating role of impulsivity. A sample of SMY (N = 85; aged 14-19; 80.6% White; 80% plurisexual) who were active nicotine users were recruited from the community. Results indicated that greater discrimination experiences were associated with more nicotine use days and higher nicotine dependence symptoms. However, impulsivity did not moderate the relationship between discrimination and nicotine use or dependence. These results highlight the potential importance of minority stress in understanding SMY's risk for nicotine use and dependence. This research suggests the need for identifying factors that could place some SMY at greater risk for nicotine use and dependence and points to potential clinical implications for nicotine cessation interventions for SMY.

Exercise as a smoking cessation treatment for women: a randomized controlled trial.

Cigarette smoking remains the leading behavioral risk factor for chronic disease and premature mortality. This RCT tested the efficacy of moderate intensity aerobic exercise as an adjunctive smoking cessation treatment among women. Participants (N = 105; age = 42.5, SD = 11.2) received brief smoking cessation counseling and 10 weeks of nicotine replacement therapy and were randomized to 12 weeks of moderate intensity exercise (Exercise; n = 53) or 12 weeks of health education (Control; n = 52). Longitudinal models, with Generalized Estimating Equations, showed no differences between Exercise and Control in cotinine-verified 7-day point prevalence abstinence (Wald = 1.96, p = 0.10) or continuous abstinence (Wald = 1.45, p = 0.23) at 12-weeks (post-treatment) or 6-, 9-, or 12-month follow-up, controlling for differences in baseline nicotine dependence. There was no effect of exercise on smoking cessation. The present study adds to the literature suggesting null effects of exercise as a smoking cessation adjunctive treatment despite promising findings in short-term laboratory based studies.

Day-level shifts in social contexts during youth cannabis use treatment.

OBJECTIVE: Social context plays a critical role in youth cannabis use. Yet few studies have examined if and when social contexts shift during cannabis use treatment. This study examined daily shifts in youths' social contexts with the goal of characterizing how specific social contexts (e.g., time with cannabis-using friends or siblings) relate to cannabis craving and use during cannabis treatment. METHOD: Participants were 65 cannabis users (51% male), ages 15-24 years, who participated in a double-blind randomized clinical trial that tested the effects of motivational enhancement and cognitive behavioral therapies plus either adjunctive pharmacotherapy or placebo on cannabis craving and use. Ecological momentary assessment (EMA) data, collected from a pre-randomization period through the completion of the six-week intervention, assessed youths' social contexts, cannabis use, and craving. RESULTS: Time-varying effects models identified shifts in social contexts during treatment. Overall, time spent with cannabis-using friends and siblings decreased, where time spent with non-using friends or alone increased across the trial. Time with parents or non-using siblings was unchanged. Comparing the relative associations of social contexts with same-day craving and use, more time with cannabis-using friends and with siblings was uniquely associated with greater craving and use. CONCLUSIONS: Social context is an important factor in youth substance-use treatment. While time spent with cannabis-using friends and siblings decreased over treatment for all participants, those who continued to spend time with using individuals reported greater craving and use. This research supports increased attention to shifting youths' social contexts to enhance treatment success. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Why don't they stop? Understanding unplanned marijuana use among adolescents and young adults.

Difficulty regulating substance use is a core feature of addiction that can manifest as unplanned use. This study sought to identify internal and situational influences on unplanned marijuana use among youth ages 15 to 24 years (N = 85; 48% female; 27% age <18 years). Additionally, we disentangled person-level associations from within-person day-to-day influences. Ecological momentary assessment methods captured affective (positive: energized, excited, sociable, happy, relaxed; negative: bored, tense, sad, stressed) and situational factors in real-world settings during a 1-week monitoring period. Participants reported no plan to use on 51% of days (269/527), and youth ultimately used marijuana on 35% of these unplanned days. At the day level, on days when youth spent more time in the presence of marijuana-related cues than they typically do, they used more grams on planned days and less on unplanned days. Regardless of use plans, youth were more likely to use on days when they spent more time with using friends and if they reported greater availability of marijuana in general across the monitoring period. At the person level, youth who generally reported higher positive affect, relative to other participants, used more on planned days and less on unplanned days. Regardless of use plans, youth who generally reported greater craving and time in the presence of marijuana-related cues used more grams, whereas youth who generally reported greater negative affect used less. Together, findings revealed several factors, with clear clinical relevance, which may explain why some youth struggle to control their marijuana use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Using Ecological Momentary Assessment to Identify Mechanisms of Change: An Application From a Pharmacotherapy Trial With Adolescent Cannabis Users.

OBJECTIVE: The present study used youth's in vivo reports of subjective responses to cannabis while smoking in their natural environments to identify real-world mechanisms of topiramate treatment for cannabis misuse. METHOD: Participants were 40 cannabis users (≥ twice weekly in past 30 days), ages 15-24 years (47.5% female), with at least one cannabis use episode during the final 3 weeks of a 6-week, randomized clinical trial. Youth reported subjective "high" while smoking, stimulation, sedation, stress, craving, and grams of marijuana used in the natural environment via wireless electronic devices. Bayesian multilevel structural equation modeling (MSEM) evaluated mediation via indirect effect tests. RESULTS: Significant within (daily) and between (person) variability and distinctive within and between effects supported the MSEM approach. Subjective high while smoking was significantly reduced for youth in the topiramate condition, relative to placebo, and the indirect effect of reduced subjective high on total grams of cannabis smoked that day was significant. Indirect effects through other subjective responses were not significant. CONCLUSIONS: The results of this initial study suggest that altering subjective responses to smoking, specifically subjective high, may be a key target for developing adjunctive pharmacotherapies for cannabis misuse. More generally, this work provides an example for applying ecological momentary assessment and analytic techniques to evaluate mechanisms of behavior change in longitudinal data.

Elevated Behavioral Economic Demand for Alcohol in a Community Sample of Heavy Drinking Smokers.

OBJECTIVE: Cigarette smokers are more likely to consume alcohol at higher levels and experience poorer response to treatment for alcohol problems than are nonsmokers. One previous study in university students suggests that a potential reason for the high overlap between alcohol and tobacco use is that concurrent smoking is associated with overvaluation of alcohol, as reflected in elevated behavioral economic demand. The present study sought to extend these initial findings in a community sample with heavier levels of alcohol and tobacco use. METHOD: Participants were 111 non-treatment-seeking heavy drinkers(defined as 18+/14+ drinks per week for men/women) from a larger study on alcohol pharmacotherapy mechanisms. Forty-nine participants (44%) reported regular smoking (≥5 cigarettes/day). Participants completed a hypothetical alcohol purchase task assessing alcohol consumption at escalating levels of price. Covariates included demographics, drinking quantity, alcohol use disorder severity, depression, and delay discounting. RESULTS: In covariate-adjusted models, smokers reported significantly higher maximum alcohol expenditures (Omax) and breakpoint price (first price suppressing consumption to zero) compared with nonsmokers. Elevated alcohol demand correlated with drinking quantity and severity in the entire sample, but not with smoking frequency or nicotine dependence among smokers only. CONCLUSIONS: This study offers further evidence of increased reinforcing value of alcohol among smokers in a sample of heavy drinkers from the community. Clinical implications and potential mechanisms underlying this relationship are discussed.

Overcoming limitations in previous research on exercise as a smoking cessation treatment: rationale and design of the "Quit for Health" trial.

Aerobic exercise has been proposed as a stand-alone or adjunct smoking cessation treatment, but findings have been mixed. Laboratory studies have shown that individual exercise sessions lead to decreases in withdrawal symptoms and cigarette cravings, but findings are limited by lack of follow-up and artificial settings. On the other hand, smoking cessation treatment RCTs have generally failed to show positive effects of exercise on smoking cessation, but have been plagued by poor and/or unverified compliance with exercise programs. This paper describes the rationale and design for Quit for Health (QFH)--an RCT designed to determine the efficacy of aerobic exercise as an adjunct smoking cessation treatment among women. To overcome limitations of previous research, compliance with the exercise (and wellness contact control) program is incentivized and directly observed, and ecological momentary assessment is used to examine change over time in withdrawal symptoms and cigarette cravings in participants' natural environments.

Olanzapine reduces urge to smoke and nicotine withdrawal symptoms in community smokers.

Olanzapine (OLAN), an atypical antipsychotic medication with mixed 5-HT2/DA antagonist properties, was predicted to dose-dependently decrease urge to smoke, withdrawal, and cigarette reinforcement in smokers without psychosis. A double-blind placebo-controlled within-subjects cross-over trial investigated the acute effects of OLAN (0, 2.5, and 5.0 mg; counterbalanced order) in 24 community smokers who underwent 10-hr smoking deprivation. Urge to smoke, tobacco withdrawal, and cigarette reinforcement were assessed with cue reactivity and behavioral choice procedures. OLAN (2.5 mg) reduced withdrawal symptoms before and during cue exposure and decreased urge associated with anticipated positive affect from smoking before and during cue exposure; 5.0 mg OLAN decreased withdrawal only when cues were included. OLAN did not affect preference for cigarette puffs versus money, smoke intake, or urge to smoke associated with negative affect relief. The results indicate a potentially beneficial effect of 2.5 mg OLAN on tobacco withdrawal and urge to smoke. Combined 5HT/DA antagonists should be considered for future development of pharmacotherapies for smoking cessation.

Effects of repeated days of smoking cue exposure on urge to smoke and physiological reactivity.

The present study investigated the effects of repeated days of laboratory-based smoking cue exposure on subjective and physiologic cue reactivity. Twenty non-treatment seeking moderate/heavy smokers completed three laboratory sessions approximately 7 days apart, each following a 10-hour nicotine deprivation period. Cue reactivity procedures consisted of a relaxation trial followed by two trials of in vivo cue exposure. Dependent measures included urge to smoke, a withdrawal questionnaire, mean arterial pressure (MAP), and heart rate (HR). A Condition (relaxation vs. cue exposure) by Day (1, 2, or 3) analysis of variance revealed a significant main effect of Condition (greater urge to smoke after cue exposure) but no significant main or interaction effect for Day. Similarly, MAP and HR change scores following cue exposure did not differ across test days. Cue-elicited changes in withdrawal symptoms were only observed on Day 1, but not when the interday interval was covaried. Results suggest that laboratory-based cue-elicited changes in urge to smoke, MAP, and HR are stable over three separate days.

Pharmacological effects of naltrexone and intravenous alcohol on craving for cigarettes among light smokers: a pilot study.

RATIONALE: Although naltrexone has been widely researched in the context of drinking and smoking behaviors, with each substance studied separately, little is known about the effects of naltrexone on craving for cigarettes during alcohol intoxication. OBJECTIVES: The present study used a within-subjects double-blind placebo-controlled design to (1) examine the effects of alcohol, administered intravenously, on craving for cigarettes; (2) test the effects of naltrexone on cigarette craving during alcohol intoxication; and (3) examine the relationship between craving for alcohol and cigarettes across rising breath alcohol concentrations (BrACs). MATERIALS AND METHODS: Heavy drinking light smokers completed two counterbalanced intravenous alcohol challenge sessions, one after taking naltrexone (50 mg) for 3 days and one after taking a placebo for 3 days. During each session, participants reported on their craving for alcohol and cigarettes. RESULTS: Analyses revealed a significant positive effect of BrAC on urge to smoke as well as a BrAC x Medication interaction. Specifically, the linear relationship between BrAC and urge to smoke was significantly weaker in the naltrexone condition, as compared to placebo. There was also a positive association between urge to drink and urge to smoke, and this relationship was moderated by BrAC. CONCLUSIONS: These findings demonstrate that the pharmacological effects of alcohol alone induce craving for cigarettes and that naltrexone blunts the progression of craving for cigarettes during alcohol intoxication. These results highlight the potential clinical utility of naltrexone for heavy drinkers trying to quit smoking.