Identifying research gaps in substance use disorder: A systematic methodology and prioritized list.

Background: This paper presents a new methodology for identifying and prioritizing research gaps, contributing to the nascent literature on systematic ways to identify research gaps. Objectives: The goal of this paper is to report on a gaps analysis of substance use disorder (SUD) research. Based on input from Military Health System stakeholders, we selected the following subtopics as priorities: alcohol use disorder (AUD) and comorbid conditions, prescription opioids, and novel synthetic drugs (NSDs), including synthetic cannabinoids, synthetic cathinones, novel synthetic opioids, and e-cigarette use. Methods: Statements of research needs were extracted from authoritative source reports. A work group of 13 subject matter experts then supplemented, consolidated, and refined the statements. Support for each statement was rated based on predetermined metrics to produce a list of high-priority potential research gaps. Work group members searched both published and ongoing research literature to determine whether these potential gaps were sufficiently addressed in the literature. Finally, to prioritize the gaps, work group members rated them on a set of metrics. Results: The work group reduced 175 statements of research needs to a list of 18 final prioritized gaps: nine for AUD, four for prescription opioids, and five for NSDs. For each topic, we present a prioritized list of gaps. Conclusions: This paper describes a method to identify and prioritize research gaps relevant to military and civilian research and presents the prioritized SUD gaps. Our methodology and findings can inform policy makers, researchers, and funding agencies as they consider investments in future research.

The separate and combined effects of alcohol and nicotine on anticipatory anxiety: a multidimensional analysis.

Individuals who smoke cigarettes are significantly more likely to smoke more when they drink alcohol. Indeed, smoking and drinking appear strongly linked, at both between- and within-person levels of analyses. Anecdotal evidence further suggests that alcohol consumption in combination with smoking cigarettes reduces anxiety, yet the mechanisms by which this may occur are not well understood. The current study assessed the separate and combined effects of alcohol and nicotine on self-reported and psychophysiological (startle eyeblink magnitude) indices of anxiety. Results indicated that alcohol provided anxiolytic benefits alone and in combination with nicotine, as evidenced by significant reductions in startle eyeblink magnitude. According to self-reported anxiety, alcohol and nicotine exerted a conjoint effect on diminishing increases in anxiety subsequent to a speech stressor. These data highlight the importance of studying both the separate and combined effects of these two widely used substances, as well as the advantages of employing a multimodal assessment of emotional response.

Positive reactions to tobacco predict relapse after cessation.

Among chronic smokers, individual differences in subjective reactions to smoking may characterize important facets of nicotine dependence that relate to abstinence-induced craving, withdrawal symptom profiles, and risk for relapse. Although the negative reinforcing properties of smoking have achieved prominent positions in models of relapse (Baker, Brandon, & Chassin, 2004), vulnerability to relapse risk may also arise from seeking positive reinforcement from smoking (Shiffman & Kirchner, 2009). In this study, 183 cessation-motivated smokers provided subjective craving, positive and negative reactions to standardized cigarettes following overnight abstinence. Level of craving, negative mood, and positive mood after overnight abstinence were significantly predictive of withdrawal on quit-day. Increased positive reactions to smoking were uniquely predictive of relapse after quitting (Hazard Ratio = 1.22, p < .001). Individual differences in positive reactions to smoking may be important markers of neurobiological systems that promote dependence and interfere with cessation efforts.

Predictors and sequelae of smoking topography over the course of a single cigarette in adolescent light smokers.

PURPOSE: The objective of this study was to determine whether adolescent smokers, who varied in their smoking histories and symptoms of nicotine dependence, exhibit any decrease in puff volume and duration similar to that typically seen in dependent adolescent and adult smokers. Moreover, we examined whether puffing trajectories were moderated by individual difference factors, as well as whether puffing topography over the course of smoking a single cigarette was predictive of an escalation in dependence symptoms. METHODS: We assessed smoking topography (puff number, duration, volume, maximum flow rate [velocity], and inter-puff interval) over the course of smoking a single cigarette in a sample of 78 adolescent light smokers, using hierarchical linear modeling. We examined moderators (anxiety, depression, nicotine dependence) of the topographic trajectories, as well as whether smoking topography predicted any change in dependence over a 2-year period. RESULTS: Puff volume and puff duration decreased over the course of smoking the cigarette, whereas puff velocity and inter-puff interval increased. Slopes for puff volume and duration were moderated by anxiety and depressive symptoms. Moreover, individuals with a less "typical" topography pattern (exhibited stable or increasing volume and duration over the course of smoking the cigarette) demonstrated a heightened dependence escalation in the subsequent 2 years. CONCLUSION: Our findings suggest that adolescent light smokers self-regulate nicotine during the course of smoking a single cigarette, similar to that reported in dependent adolescent and adult smokers. However, single cigarette self-regulation was influenced by certain affective factors. Implications of these findings and future directions for adolescent smoking research are discussed.

The separate and combined effects of nicotine and alcohol on working memory capacity in nonabstinent smokers.

Research indicates that nicotine and alcohol are often used on the same occasion. However, the reasons for their concurrent use are not well understood. We hypothesized that one reason smokers use tobacco when they drink alcohol is to compensate for alcohol's negative effects on processing capacity with nicotine's enhancement of processing capacity. As such, the present study tested this theory by using an independent groups design to examine the separate and combined acute effects of alcohol and nicotine on working memory (WM) capacity. Nonabstinent daily smokers (n = 127) performed the counting span task (CSPAN) after consuming either an alcohol (men: 0.8 g/kg; women: 0.7 g/kg) or placebo beverage and smoking either nicotinized (1.14 mg nicotine, 15.9 mg tar) or denicotinized (.06 mg nicotine, 17.9 mg tar) cigarettes. Analyses revealed that smokers who smoked the nicotinized cigarettes performed significantly worse on the CSPAN task than smokers who smoked the denicotinized cigarettes. Although there was no main effect of alcohol on WM performance, women exhibited better WM performance than men after consuming alcohol whereas men performed better than women on the WM task after consuming the placebo beverage. Findings also revealed no interaction between the two substances on WM performance. Taken together, results suggest that nicotine impairs nonabstinent smokers' verbal WM capacity and that gender moderates the effects of alcohol on WM. Furthermore, the present findings failed to support the notion that nicotine compensates for alcohol-related decrements in working memory capacity.

Smoking, arousal, and affect: the role of anxiety sensitivity.

PURPOSE: Despite evidence that smoking elevates peripheral autonomic nervous system activity, cigarette smokers commonly report smoking to reduce negative affect, or "calm down." Studies suggest that anxiety sensitivity is positively associated with the use of anxiolytic substances, but anxiety sensitivity is also characterized by aversive responding to elevations in physiological arousal. As such, anxiety sensitivity may be an important factor in the study of smoking, affect, and arousal. METHOD: Smokers smoked cigarettes in two experimental sessions: a Stressful Speech Condition and a No Stress Condition. Psychophysiological and self-report served as within-subjects, repeated measures. RESULTS: Findings revealed that smoking reduced anxiety in high anxiety sensitive smokers who smoked during a stressful situation, but not a no stress situation. Low anxiety sensitive smokers endorsed anxiolysis in both conditions. CONCLUSIONS: Results suggest that high anxiety sensitive smokers may be sensitive to the physiologically arousing effects of smoking in low stress, low arousal, situations.

The acute effects of nicotine on positive and negative affect in adolescent smokers.

Although adolescent cigarette smoking remains a critical public health concern, little is known about the reinforcing mechanisms governing smoking in this vulnerable population. To assess predictions derived from both positive and negative reinforcement models of drug use, the authors measured the acute effects of nicotine, as administered via tobacco cigarettes, on both positive and negative affect in a group of 15- to 18-year-old smokers. A matched group of nonsmokers served as a comparison group. Findings revealed that whereas adolescents who smoked a cigarette experienced reductions in both positive and negative affect, the observed reductions in negative affect were moderated by nicotine content of the cigarette (high yield vs. denicotinized), level of nicotine dependence, level of baseline craving, and smoking expectancies pertinent to negative affect regulation. Nonsmokers experienced no change in affect over the 10-min assessment period, and no interaction effects were observed for positive affect. Overall, the findings conform to a negative reinforcement model of nicotine effects and strongly suggest that, even among young light smokers, nicotine dependence and resultant withdrawal symptomatology may serve as motivating factors governing smoking behavior.

Smoking topography in response to denicotinized and high-yield nicotine cigarettes in adolescent smokers.

PURPOSE: The objective of this study was to explore the smoking topography of adolescent smokers. It is well established that the majority of adult nicotine-dependent smokers began smoking as adolescents. Whereas recent advances have been made with respect to identification of factors that predispose to nicotine dependence, very little is known about the actual smoking behavior (e.g., topography) of adolescent smokers, or its relationship to nicotine dependence. Correspondingly, the extent to which adolescent smokers smoke to obtain nicotine is also unknown. METHODS: In the present study, we assessed several topographical indices of smoking (e.g., puff volume, puff number) in a sample of 35 light, adolescent smokers. Moreover, we examined whether smoking behavior is different in response to smoking a denicotinized relative to a high-yield, nicotine cigarette. RESULTS: All participants evidenced a significant increase in expired air carbon monoxide after the smoking of a cigarette. Results of independent-sample t-tests revealed that adolescents who smoked a low-yield nicotine cigarette took significantly more puffs per cigarette than did those who smoked a high-yield cigarette. CONCLUSIONS: These findings suggest that adolescent smokers do titrate their nicotine intake in response to smoking denicotinized cigarettes, but do so not by taking larger puffs or smoking more quickly, but by simply taking more puffs per cigarette. Implications of the findings and future directions for this type of research with adolescents are discussed.